Overview
Targeted nanoparticle for head and neck cancers: overview and perspectives Yuying Zhao,1,2† Haolin Chen,1,2† Xing Chen,2† Geoffrey Hollett,3 Zhipeng Gu,2* Jun Wu2,4* and Xiqiang Liu1* Head and neck cancer (HNC) is common in several regions and is associated with high morbidity and mortality worldwide. This review summarizes the recent progress in the development of targeted nanoparticle systems for HNC therapy. © 2017 Wiley Periodicals, Inc. How to cite this article:
WIREs Nanomed Nanobiotechnol 2017, e1469. doi: 10.1002/wnan.1469
INTRODUCTION
H
ead and neck cancer (HNC) refers to malignant neoplasms that develop in the oral cavity, larynx, pharynx and thyroid. As shown in Figure 1, an estimated 842,000 new cases of HNC arose in 2012, accounting for 11.9% of cancers worldwide. In the same year, there were 319,300 deaths due to HNC, accounting for 4.5% of all cancers.1,2 HNC patients regularly have been reported to have dysphagia, respiratory disorders, xerostomia and other symptoms, which will be worse due to the lack of appetite, weight loss, and nutritional deficiency.3 Tobacco and alcohol consumption were found to be the biggest culprit of squamous cell carcinoma of the head and neck (HNSCC) by numerous epidemiologic studies, along with areca chewing, mate drinking and so †
These authors contribute equally to this work.
*Correspondence to:
[email protected], wujun29@mail. sysu.edu.cn,
[email protected] 1
Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University,Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, PR China
2
Key Laboratory of Sensing Technology and Biomedical Instrument of Guangdong Province, School of Engineering, Sun Yat-sen University, Guangzhou, PR China
3
Materials Science and Engineering Program, University of California San Diego, La Jolla, CA, USA
4
Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, Sun Yat-sen University, Guangzhou, PR China Conflict of interest: The authors have declared no conflicts of interest for this article.
on.4,5 In the past few decades, human papillomavirus (HPV) (particularly HPV16 and HPV18) infection has led to a new type of HNC patient who is young and does not drink nor smoke.6,7 HPV infection is common in cervical carcinoma via sexual contact. As a result of changes in sexual intercourse, it is predicted that by 2020, more than half of HPV associated patients are HNC sufferers, significantly surpassing the number of cervical carcinoma.6,8,9 Compared with HPV-negative patients, HPV-positive patients have improved treatment outcomes. For example, two-year survival rates of oropharynx cancer for HPV-positive and HPV-negative patients are 95% and 62%, respectively, and 79% and 46%, respectively after five years.7,10,11 The accurate diagnosis and standardized classification of the extent of a cancer is significantly important to plan viable therapeutic regimens by referring to prior cases with a similar prognosis. The tumor node metastasis (TNM) cancer staging system is the most commonly used classification that considers the local tumor growth degree, the spread to regional lymph nodes and the other organ metastases. HNC can take place in a number of regions including the lip and oral cavity, nasopharynx, oropharynx, hypopharynx, supraglottis, glottis, subglottis, maxillary sinus, nasal cavity and ethmoid sinus and thyroid (Figure 2). They all have unique cancer grading standards according to the 8th Edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual which is published in cooperation with the International Union for Cancer Control. Herein we summarize the classification of HNC from
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The incidence is higher in male
842,000 New cases of head and neck cancer
319,300 Death toll of head and neck cancer
Tobacco
Alcohol OLD
11.9%
CAUSING CULPRITS
4.5%
NEW
Incidence rate of all cancers
It is predicted that by 2020, more than half of HPV associated patients are HNC, surpassing the cervical cancer patients.
Death rate of all cancers
HPV infection
FI GU RE 1 | Head and neck cancer statistics worldwide. stage 0 to stage IV.12 Stage 0, tumors have definite shapes and clearly separate from the surrounding normal tissues, no invasion or metastasis. Stage I, tumors retain its shape with less than 2 cm in diameter, have not push through the submucosa. Stage II, cancer cells push through or between adjacent normal cells and the diameter of tumor is between 2 cm and 4 cm. Stage III, cancer cells rapidly divide and multiply, extend to the local lymph nodes, the size of the tumor is more than 4 cm. Stage IV, cancer cells get into the bloodstream to other regions, results in metastases. As mentioned above, HNC is a complex and difficult disease that can easily infiltrate surrounding systems and induce metastasis. In the clinic, they are usually treated by surgery, radiotherapy and chemotherapy. The intractable threats to HNC patients are cancer recurrence and metastasis. Scattered
Oral cavity Tonsil Posterior pharynx Base of tongue
F I G U R E 2 | Anatomic subsites of some common primary sites of HNC.
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distribution of chemotherapeutic drugs in the body greatly restricts the application of chemotherapy. The arising applications of nanotechnologies in biomedicine provide new opportunities for dealing with the problems of drugs used in cancer treatments.13–17 Nanoparticle (NP) drug carriers can be composed of polymers, liposomes, dendrimers, carbon, and other metal or metal oxides.18–26 The size of the NPs used in chemotherapy is typically between 1 nm and 200 nm to ensure that they can be took by tumor cells effectively.27,28 The preferential uptake of drug-containing NPs into tumor cells is highly desirable for suppressing systemic side effects, but only if it can be controlled.29–33 Targeted NP delivery systems can be divided into two mechanisms: passive and active targeting. Passive targeting is based on the enhanced permeability and retention (EPR) effect, in which the poorly formed, leaky vasculature of the tumor site causes drug-loaded NPs to accumulate locally. However, the main limitation of passive targeting is insufficient drug concentration at the tumor site. In contrast, NPs decorated with tumor specific targeting moieties participate in active targeting. Specific ligands allow for the particle to interact more strongly with specific cell types, thus allowing for NPs to deliver a payload directly to a tumor cell with minimal drug leeching into general circulation. This carrier strategy maximizes the drug concentration inside the tumor, meaning that a lower overall dose can be administered to the patient while maintaining therapeutic efficacy.19,34–36 Active targeting NPs have shown tremendous promise as drug delivery systems and are presently being pursued as chemotherapy carriers in all types of cancers.26,37 The successfully design and widely use of targeted NPs are usually governed by the selected coupling reaction.38–40 Herein we describe the current status of targeted NPs applied to chemotherapy of
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Targeted nanoparticle for head and neck cancers
HNC and discuss their potential future clinical application.
CURRENT ADJUVANT CHEMOTHERAPY AGAINST HNC For early stage HNC patients, surgical resection is the ideal treatment option. But for the patients in terminal stages, a combined comprehensive, multimodality of treatment is advocated instead of surgical resection. The use of chemotherapy can be divided into three techniques: induction chemotherapy, synchronous chemotherapy and adjuvant chemotherapy. Induction chemotherapy, also called neoadjuvant chemotherapy is used before surgery to reduce the volume of tumors to improve surgical outcomes. Synchronous chemotherapy is aimed to enhance the efficiency of radiotherapy, while simultaneously reducing the risk of lymph node metastasis. The purpose of adjuvant chemotherapy is to kill the small lesions that cannot be removed by surgery or reduce recurrence and improve survival rate. In recent years, the drugs fluorouracil (5-FU), methotrexate (MTX), bleomycin, mitomycin C, hydroxyurea, cisplatin and carboplatin were employed in the research of HNC therapeutic treatment.17,41 From the current literature, platinum-5-FU chemotherapy is regarded as the backbone of the current standard treatment. The platinum-5-FU chemotherapy system was first utilized by the Southwest
Oncology Group (SWOG) who compared the efficacy of cisplatin with 5-FU, caboplatin with 5-FU, and single-agent MTX in HNC patients who were suffering the recurrence and metastasis. The study reported complete and partial response rates is 32% for cisplatin/5-FU, 21% for carboplatin/5-FU, and 10% for MTX, although the median survival rate in those three treatment plans are the same. It should be noted that despite the highest response rate, the cisplatin/5FU group reported higher incidences of systemic side effects.42 At the same time in 2004, European Organization for Research and Treatment of Cancer (EORTC) and Radiation Therapy Oncology Group (RTOG) published its trails about the treatment of HNC patients. RTOG 9501 conducted a random experiment of HNC patients treat after surgery resection. The group treated with radiotherapy plus cisplatin [100 mg per square meter of body-surface area intravenously (I.V.) on day 1, 22, and 43] gained high two-year survival rate and disease-free survival rate than the group received radiotherapy alone.43 EORTC 22931 conducted almost the same trails except some parameter differences, also showed a significant benefit of overall survival for radiotherapy plus cisplatin group.44 These two landmark trails established the role of chemotherapy. Currently, the molecularly targeted agent, cetuximab, is also expected to play a significant role in the future treatment of HNC (Figure 3). The emerging of new therapeutic drugs and developing of chemotherapy pave the way to improve the treatment effect of HNC.
Cetuximab or lapatinib
Radiotherapy alone Original ajuvant therapy
He
ad
Induction chemotherapy
er
Antibody against EGFR
a n d n eck ca
nc
Docetaxel, cisplatin plus 5-fluorouracil
Chemoradiotherapy
Cisplatin plus radiotherapy
FI GU RE 3 | Illustration of adjuvant therapy of HNC. Radiotherapy was the standard treatment care for resectable HNC. While now cisplatin plus radiotherapy is the mainstay of HNC. Docetaxel, cisplatin plus 5-fluorouracil (TPF) is the standard regimen for induction chemotherapy. Cetuximab/lapatinib is the monoclonal antibody against the ligand binding domain of EGFR.
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NANOPARTICLES IN HNC THERAPY Materials Requirements for HNC Therapy
C
O
NH
O
C
H
O
O
NH
CO
C
C
HOOC
NH
NH
HOOC
O
H N
Emerging nanotechnologies offer new pathways of biomedical applications for cancer diagnosis and therapy.45–49 NP-based delivery vehicles with precise control of size, shape, and surface functionalization are providing new avenues to carry multiple diagnostic and/or therapeutic agents for better outcomes and fewer side effects. Taking advantage of the unique properties of materials at the nanoscale, such as large surface area to volume ratio, novel optical and magnetic properties, facile modification, nanomaterials have been explored to overcome a lot of biological barriers to cancer treatment (Figure 4).20,28,50,51 However, before employed in the cancer therapy, nanomaterials are required to have excellent biocompatibility, well biodegradation and low toxicity. Furthermore, nanomaterials must have the ability to load sufficient drugs and accurately deliver to the tumor sites. For these application qualifications, various materials are exploited including polymers, liposomes, dendrimers, carbon, and other metal or metal oxides. Herein we choose some representative examples to have an overview of nanomaterials used in HNC therapy.
O
C
C
O CO
HOOC
H N
O
C
H
O
H
C
N
O
O
N
C
H
C
HN
O
HN OC
HO
PEG
Amphiphilic block polymer
EGFR vIIIAb
F I G U R E 4 | Illustration of nanoparticles modified with targeted groups. EGFR vIIIAb was attached on surface of Amphiphilic block polymer nanoparticles for specific targeting to the tumor site.
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In the area of HNC research, the novel physiochemical properties of gold NPs, such as localized surface plasmon resonance (LSPR), enhanced light scattering, and photo-thermal and photo-acoustic properties52,53 have generated significant attention for developing diagnostic platforms and effective treatments in HNC.54–57 Similarly, carbon-based nanovectors were used to load paclitaxel, which was selected as a classic example of a water insoluble drug with high therapeutic efficacy and severe off-target toxicity. At the same time, the molecularly targeted agent cetuximab combined has yielded synergistic effects, deserving of further preclinical development for HNC therapy.58,59 Bhirde reported that carbon nanotubebased drug delivery system holds great promise for cancer therapy. They reported in vivo targeted cancer treatment by attaching the anticancer agent cisplatin along with epidermal growth factor (EGF) to a single wall carbon nanotube (SWNT) (Figure 5).60 Induced hyperthermia via magnetic iron oxide (IO) NP (~15 nm in diameter) was explored for treatment of HNC using a mouse xenograft model of HNSCC cell line (Tu212). IO NPs generate hyperthermia using alternating magnetic fields for cell killing, providing a new option to the existing HNC treatment approaches.61 Xie et al. developed a folateconjugated cisplatin-loaded magnetic nanomedicine (CDDP-FA-ASA-MNP) and used it as a magnetic resonance imaging (MRI) contrast agent while simultaneously delivering a chemotherapeutic drug, providing an alternative platform for drug delivery in HNSCC patients and lays the foundation for molecular targeted treatment of cancer.62 Carboxyl functionalized IO NPs conjugated with a fibronectin-mimetic peptide (Fmp) were combined with a second-generation photodynamic therapy (PDT) drug (Pc), showing obviously inhibition of tumor growth at lower dose, which showed great potential to serve as both MRI agent and PDT drug in the clinic (Figure 6).63 Polymeric NPs were also used for delivering medicinal drugs and bioactive molecules showing significant therapeutic value. Matthew S. Brown used sub–50-nm tenfibgen nanocapsules to deliver antiCK2α/α0 oligodeoxynucleotide, showing significant suppression of tumor growth, CK2 effects on NFκB–mediated and TP53-mediated signal activation with corresponding gene and protein expression in vivo.64 Diblock copolymers were used to effectively deliver small interfering RNAs (siRNA) targeting a proapoptotic gene and proved to be effective in conferring radioprotection to the salivary glands.65 Colley proved the ability of pH-sensitive poly 2-
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Targeted nanoparticle for head and neck cancers
(a) 2N
Pt
NH
Pt
O
NH2
O
NH
O
2
Pt
CI
CI HN 2 Pt NH
O
Pt
NH2
CI
O NH2
O O
2
O O
CI
O
CI
NH2
Pt
CI
NH2
O
O
N
H
2
CI
O
O
OH
O
O
Pt
NH2
N
O
O
O
OH
OH
O
NH2
Pt
O
OH
2N
Pt
Pt
O
H
O
OH
EGF, Qdot
O
Pt
O
NH
EDC
NH2
O
2
CI
H
2N
Pt
O
NH2
CI
O
Pt
NH2
O
NH
O
2
O O
CI
Pt
H
2
O
O
Qdot
NH2
Pt
O NH2
N
DDS: SWNT+Cispiatin+EGF
Cancer cell surface
O
2
CI
2N
CI
O
O
NH
H
CI
H2N
CI
H
O
O
NH2
O
2
DDS
NH2
Pt
O NH2
O
O
Pt
CI
O
Pt
CI
O
NH
NH2
Pt
OH
2N
2N
NH2 O
CI
OH
O
CI
H
O
2
H
O
2
O
Pt
NH
EGF, Cispiatin O
NH
NH2
Pt
O
2
2N
Pt
H
H
O
2
CI
EDC
O
2N
CI
O
H2N
CI
H
Pt
O
(b)
NH2
H2N
CI
H
CI
NH2
Pt
CI
EGF: Epidermal growth factor
EGFR: Epidermal growth factor receptor
FI GU RE 5 | Nanotube-based delivery system. (a) Illustration of modified the carboxylated SWNTs (in green) surface with EGF, cisplatin, and Qdots. (b) Schematic presenting the SWNT bundles bioconjugated with EGF and cisplatin recognized by the receptor EGFR on a HNSCC cell surface. (methacryloyloxy) ethyl phosphorylcholine (PMPC)poly 2-(diisopropyl-amino) ethyl methacrylate (PDPA) polymersomes to encapsulate chemotherapeutic agents (doxorubicin and paclitaxel) for effective combination anticancer therapy. The uptake and ability to deliver encapsulated drugs via polymersomes were measured in two and three- dimensional culture systems (Figure 7).66 Wang evaluated the effectiveness of poly (lactic-co-glycolic acid) (PLGA)
NPs assisted 5-aminolevulinic acid (ALA) delivery for topical PDT of cutaneous SCC.67 Changa et al. conjugated the anticancer drug mitoxantrone (MTO) to palmitoleic acid, generating two types of palmitoleyl MTO (Pal-MTO) lipids: monopalmitoleyl MTO (mono- Pal-MTO) and dipalmitoleyl MTO (di-Pal-MTO) at the molar ratio of 1:1 (md11-Pal-MTO NPs) showed the most efficient cellular delivery of siRNA.68 Yu et al. formulated
NH 2 NH 2
NH 2
O
C
C
OH
O
O
C
C
O
OH
O
C
C
O
C O
NH2
C
O O
C
C
C
C
NH2
NH2
C
O
O
C
O C
O C OH
O
O C O H
O H
OH
H
O
O
NH
2
O
C
O
OH
NH2
Nano core
C
C
FMP-IO
O
O C
O C
O
IO
OH
O C
C
OH
O
FMP-IO-PC4
FMP
PC4
FI GU RE 6 | Schematic illustration of the preparation of water-soluble FMP-IO-PC4 nanoparticles which can serve as both a MRI agent and PDT drug.
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F I G U R E 7 | pH-sensitive poly 2-(methacryloyloxy) ethyl phosphorylcholine (PMPC)- poly 2-(diisopropylamino) ethyl methacrylate (PDPA) polymersomes used as drug delivery vehicles for effective combinational anticancer therapy. 1,2-dioleoyl-sn-glycero-3-ethylphos-phocholine-based cationic solid lipid nanoparticles (cSLN) containing paclitaxel and siRNA, which demonstrated the potential of cSLN for the development of co-delivery systems of lipophilic anticancer drugs and therapeutic siRNAs (Figure 8).69 Piao et al. determined the cationic lipid NPs could deliver pre-miR-107 (NP/premiR-107) with excellent efficiency (Table 1).70
Nanostructure Requirements for HNC Therapy A broad spectrum of innovative nanostructure has been developed recently for addressing various challenges in HNC, such as polymers, peptides, liposomes, dendrimers, albumin conjugates and so on.71–74 These materials are obviously vary in
Cationic lipid
PEG-DSPE
morphologies and structures. From two-dimensional nanostructures to three-dimensional nanospheres, from positive charge to negative charge of the surface, materials can present different properties. Ideal materials for HNC cancer therapy are desired to be flexible to change its sizes, morphologies, surface properties and so forth. Rait et al. improved the antisense HER-2 oligonucleotide (AS HER-2 ODN) delivery to tumor cells by complexing the AS HER-2 ODN with their previously established folate-liposome delivery system, which resulting in sensitization of HNC cells to chemotherapeutic agents.75 Matthew S. Gayong Shim et al. synthesized trilysinoyl oleylamide (TLO)-based liposomes (TLOL) for systemic siRNA and drug delivery.76 Zhu et al. chose a polymer family equipped with cationic and hydrophobic characters
siRNA
Paclitaxel
F I G U R E 8 | Illustration of the cSLN nanoparticles loaded with paclitaxel and siRNA. EcSLN (a) and PcSLN (b) were used as co-delivery system of lipophilic anticancer drug and therapeutic siRNAs.
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Targeted nanoparticle for head and neck cancers
TABLE 1 | An Overview of Various Nanomaterial-based Platforms in Head and Neck Cancer Treatment Nano-platform
Treatment
Targeting Moiety Application
Ref.
Gold
Diagnosis, Photodynamic therapy, Photothermal therapy
EGFR
Optical imaging, targeted therapy
52–57
Carbon
Drug delivery vehicle
Cetuximab
Targeted drug delivery
58,59
SWNTs
Drug delivery vehicle
EGFR
Targeted drug delivery
60
Magnetic
Hyperthermia therapy, Photodynamic Therapy,
Folate receptors, integrin β1
Magnetic resonance imaging, Targeted therapy
61–63
Polymeric Gene therapy, Photodynamic therapy nanoparticles (NPs)
RNA, Salivary receptors
Targeted delivery, Radioprotection using small-interfering RNA (siRNA)-based gene silencing
64–67
Lipid
RNA
Genetic vector
68–70
Gene delivery
to prepare a novel NP which can decorate with protein ligands outside and carry therapeutic proteins inside the particle.21 Ward et al. used a G5 polyamidoamine dendrimer conjugated to the targeting moiety folic acid (FA) for targeted chemotherapy.77 Dosio et al.78 conjugated the anticancer agent paclitaxel to human serum albumin (HSA) to form drug– albumin conjugate and then decorated with FA, which demonstrated increased selectivity and antitumoral activity.
TARGETED NANOPARTICLES DELIVERY FOR HNC THERAPY Targeted Delivery Strategy for HNC Therapy Passive diffusion is the major internalization mechanism of free drugs into tumor cells, whereas NPs enter cells primarily via endocytosis, avoiding the drug refluxing back out of the cell.79 Controlling the particle–cell interaction is one of the most important reasons for NP modification, allowing for targeting ligands such as antibodies and their fragments, nucleic acid strands, peptides and other small molecules.80,81 Epidermal growth factor receptor (EGFR) is often over-expressed in HNSCC cases.82 High levels of EGFR expression are associated with poor prognosis in a variety of cancers, mostly in HNSCC, indicating that receptor directed therapies may be useful as anticancer strategies. He et al. investigated the intratumoral transfer of cationic liposome-mediated antisense EGFR plasmids into HNSCC subcutaneous xenografts through in situ expression of antisense oligonucleotides, which resulted in increased tumor cell apoptosis and inhibition of tumor growth.83 Cho et al. developed a poly-L-arginine (PLR) and dextran sulfate (DEX) based nano-sized polyelectrolyte
complex (nanocomplex) for delivery of epidermal EGFR-siRNA in a HNSCC model. Their experiments showed highest EGFR gene silencing efficiency in both Hep-2 and FaDu cell lines and exhibited excellent tumor growth inhibition in a tumor xenografted mouse model.84 As described above, EGFR can also serve as a target for drug delivery. Ashwin et al. demonstrated that EGF-decorated SWNTs specifically target squamous cancer as a delivery system for cisplatin chemotherapy, which resulted in more rapid cell internalization and distinct regression of tumor growth compared to a nontargeted SWNT-cisplatin.60 Berlin et al. combined paclitaxel-loaded poly(ethylene glycol) functionalized hydrophilic carbon clusters (PEG-HCCs) NPs with cetuximab, a targeting monoclonal antibody that exclusively binds to the EGFR. The targeted nanovector systems have shown high therapeutic efficacy to be a new therapy for HNSCC.58,59 Folate acid receptors (FRs) are glycosylphosphatidylinositol-anchored cell surface receptors with a high affinity for FA, which are overexpressed in a wide range of malignant cancers, such as breast, ovarian, lung, kidney, head and neck and so forth.85 Folate acid is a water-soluble B vitamin, critical for DNA synthesis. FA retains its ability to bind with FRs after conjugation with other structures, and often improves endocytosis through the FR-mediated pathway. As such, the FR pathway has been studied extensively as a target for NP therapeutics.86 Wang et al. synthesized targeted polymeric NPs (HFT-T) loaded with additional paclitaxel, to enhance the antitumor efficacy and selectively recognize the FRpositive HNSCC KB-3-1 cell line in vitro and in vivo. The resulting NP, HFT-T, markedly inhibited tumor growth without showing a resurgence of tumor growth after several weeks treatment.75 Ward et al. fabricated acetylated generation 5 dendrimers conjugated to FA and the therapeutic MTX, then
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administered to SCID CB-17 mice inoculated with UM-SCC-1, UM-SCC-17B, and UM-SCC-22B cancer cells, showing increased treatment efficacy.77
Administration Routes for HNC Therapy It is the most simple and rapid method to administer chemotherapy drugs into systemic circulation by I.V. route. It is compatible with most hydrophilic chemotherapy agents, ensuring the low risk of infection. However, the I.V. route also has its disadvantages, for example, it is inappropriate for patients to selfadminister and not suitable for most of the hydrophobic anticancer drugs.81,87 Nanomaterials are developed to accurately send the drugs to the tumors by passive (EPR effect) and active targeting. It seems to be the best alternative that poor water solubility drugs loaded in nanomaterials to enhance drugs solubility and bioavailability. One example comes from Wang et al., who has developed a targeted NP platform that combines Pc 4, a second-generation PDT drug, with a cancer targeting ligand and IO NPs. Fmp-IO-Pc 4 administrated by I.V. injection had significantly higher tumor retention than free Pc 4, showing great potential in MRI and PDT in the clinic.63 Piao et al. used the cationic lipid NPs to deliver pre-miR-107 (NP/pre-miR107) in HNSCC cells in vitro and in vivo. The results showed that NP/pre-miR-107 could increase the delivery of miR-107 into HNSCC cells by more than 80,000-fold comparing to free pre-miR-107. NP/premiR-107 was injected I.V. through the tail vein. The results suggested that cationic lipid-based NP delivery of pre-miR-107 could suppress the tumorigenesis of HNSCC efficiently.70 Recently, studies have shown that intraperitoneal (IP) administration can be more valid than administered I.V. for some solid tumors therapy.88–90 Here, Zhao et al. reported an efficient drug delivery system based on a monomeric self-assembled nucleoside nanoparticle (SNNP). Comparing with free 5FU, SNNP loaded with 5-fluoro-uracile (5-FU-SNNP) remarkably retarded the tumor growth and SNNP alleviated the toxic side effects of 5-FU. In this experiment, IP injection was used to evaluate the biosafety of SNNP and Antitumor Efficacy Assay in vivo. The findings suggested that 5-FU has better antitumor efficacy and lower side effects when loaded with SNNP, indicating that SNNP can efficiently act as a promising nanomaterial that may witness wide clinical applications in the future.91 Intratumoral Injection is a kind of local injection, which offering some advantages, such as stabilization of drugs at tumor site, preservation of anticancer activity, controlled and prolonged drug 8 of 13
release and so on.92 Chang et al. has developed new modality of anticancer therapy that combines treatment of anticancer drugs and siRNAs. The anticancer drug-derived lipids formed cationic NPs for siRNA complexation. For siRNA treatment, siGL2 or siMcl-1 complexed to md11-Pal-MTO NP was injected intratumorally, showing the most efficient cellular delivery of siRNA.93 Intraarterial infusion is particularly compatible for regional chemotherapy, which get high drug accumulation in the tumor site.94 The significant advances in vascular radiology techniques and new devices, such as fluoroscopy units and angiographic catheters, have made it possible that intra-arterial chemotherapy more safe and accurate.95,96 However, there still remains the risk of infection and thrombosis.97 Intra-arterial infusion was conducted to study a novel NP albumin-bound paclitaxel about its efficacy and safety of intra-arterial induction chemotherapy. Two to four cycles of albumin-bound paclitaxel NP were infused into the external carotid artery or one of its branches, then, response was evaluated by physical examination, multi-detector computed tomography and also by positron emission tomography. The response rates and tolerability of intraarterial chemotherapy with NP albumin-bound paclitaxel demonstrated that the feasibility and efficacy alone or in combination with other agents in advanced HNSCC.98 Retroductal injection is used by Szilvia Arany. PH-responsive NPs complexed with siRNAs were introduced into mouse submandibular glands (SMG), which induced siRNA-based gene silencing. In this way, this method protects the SG from radiation-induced apoptosis.65
CONCLUSION Currently, nanotechnologies are widely used in numerous aspects of materials. Especially in nanomedicine, nanomaterials are employed for cancer detection and therapy due to its excellent properties. For HNC therapy, nanomaterials have the potential to enhance the efficiency of chemotherapy without increasing toxicities. As shown in Figure 9, current chemotherapeutic agents for HNC treatment are shown to be effective, but it hides some shortcomings, such as failing to accumulate an efficient dose at the tumor site while accumulating the cytotoxic drug in healthy tissues. The application of targeted NPs as drug carriers in HNC is paving the way for chemotherapy to be employed in the treatment of terminal patients, in order to alleviate their pain and prolong their life. This therapeutic regimen has attracted great attention. In recent years,
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Targeted nanoparticle for head and neck cancers
Past (a)
Present (a)
Future
Evaluate the situation of the patients, plan the treatment protocols. Surgical removal of the tumor is the preferred treatment.
Check the tumor site Based on TNM staging, identify the mode of operation
(a)
Different kinds of therapy were called
Radiotherapy Chemotherapy Immunotherapy
Cancer cell
(b) Tumor
(b)
Adjuvant therapies after the surgery Radiotherapy
Surgery to remove the tumor
Cisplatin
(c)
Mix of docetaxel, cisplatin and 5-fluorouracil
Radio Radiotherapy used as adjuvant treatment
Cetuximab or lapatinib
(b)
Targeted nanoparticles used in chemotherapy
Targeted nanoparticles Accumulated in the tumor site
Controlled release
High efficiency and low toxicity
FI GU RE 9 | The past, present and future of the treatment of head and neck cancer. Past, work includes (a) examining the tumor site and identifying the mode of operation based on TNM staging; (b) surgery to remove the tumor; and (c) use of radiotherapy as adjuvant treatment. Present, on-going treatment consists of (a) examining the tumor site and establishing the operation plan; (b) combining radiotherapy and chemotherapy as adjuvant therapies. Future, promising strategies include (a) combining more kinds of treating strategies to optimize the efficiency; (b) employing targeted nanoparticles to deliver the drug in order to improve drug efficiency and decrease off-target effects. many kinds of materials with nanoscale dimensions have been exploited to use as a targeted delivery system. Although most of targeted NP-based drug delivery systems have not been translated for clinical use, there remains a great promise to cater to the needs of HNC therapy. Future investigations of targeted NP delivery system are developing to be more effective
against cancer while being milder on other tissues. With the continuous research of nanomaterials and development efforts of HNC therapy, we expect nanomaterial based chemotherapy will improve the diagnosis, treatment, and prevention of HNC. Which will further bring tremendous impact on human health in the near future.
ACKNOWLEDGMENTS This work was supported by the Thousand Talents Plan for Young Professionals, National Natural Science Foundation of China (81372885), Guangdong Innovative and Entrepreneurial Research Team Program (2013S086), Guangdong Natural Science Foundation (2014A030312018), Science and Technology Planning Project of Guangdong Province (No. 2016A010103015), and the Major Special Research Collaborative Innovation of Guangzhou (201604020160).
REFERENCES 1. Torre LA, Bray F, Siegel RL, Ferlay J, LortetTieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015, 65:87–108.
2. Kang H, Kiess A, Chung CH. Emerging biomarkers in head and neck cancer in the era of genomics. Nat Rev Clin Oncol 2015, 12:11–26.
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3. Bressan V, Stevanin S, Bianchi M, Aleo G, Bagnasco A, Sasso L. The effects of swallowing disorders, dysgeusia, oral mucositis and xerostomia on nutritional status, oral intake and weight loss in head and neck cancer patients: a systematic review. Cancer Treat Rev 2016, 45:105–119. 4. Goldenberg D, Lee J, Koch WM, Kim MM, Trink B, Sidransky D, Moon CS. Habitual risk factors for head and neck cancer. Otolaryngol Head Neck Surg 2004, 131:986–993. 5. Hashibe M, Brennan P, Chuang SC, Boccia S, Castellsague X, Chen C, Curado MP, Dal Maso L, Daudt AW, Fabianova E, et al. Interaction between tobacco and alcohol use and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. Cancer Epidemiol Biomarkers Prev 2009, 18:541–550. 6. Deschler DG, Richmon JD, Khariwala SS, Ferris RL, Wang MB. The “new” head and neck cancer patientyoung, nonsmoker, nondrinker, and HPV positive: evaluation. Otolaryngol Head Neck Surg 2014, 151:375–380. 7. Young D, Xiao CC, Murphy B, Moore M, Fakhry C, Day TA. Increase in head and neck cancer in younger patients due to human papillomavirus (HPV). Oral Oncol 2015, 51:727–730.
Zamboni WC, DeSimone JM. Nanoparticle drug loading as a design parameter to improve docetaxel pharmacokinetics and efficacy. Biomaterials 2013, 34:8424–8429. 15. Rocca JD, Werner ME, Kramer SA, HuxfordPhillips RC, Sukumar R, Cummings ND, ViveroEscoto JL, Wang AZ, Lin W. Polysilsesquioxane nanoparticles for triggered release of cisplatin and effective cancer chemoradiotherapy. Nanomedicine 2015, 11:31–38. 16. Sethi M, Sukumar R, Karve S, Werner ME, Wang EC, Moore DT, Kowalczyk SR, Zhang L, Wang AZ. Effect of drug release kinetics on nanoparticle therapeutic efficacy and toxicity. Nanoscale 2014, 6:2321–2327. 17. Wang EC, Min Y, Palm RC, Fiordalisi JJ, Wagner KT, Hyder N, Cox AD, Caster JM, Tian X, Wang AZ. Nanoparticle formulations of histone deacetylase inhibitors for effective chemoradiotherapy in solid tumors. Biomaterials 2015, 51:208–215. 18. Kamaly N, Yameen B, Wu J, Farokhzad OC. Degradable Controlled-Release Polymers and Polymeric Nanoparticles: Mechanisms of Controlling Drug Release. Chem Rev 2016, 116:2602–2663. 19. Bertrand N, Wu J, Xu X, Kamaly N, Farokhzad OC. Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology. Adv Drug Deliv Rev 2014, 66:2–25.
8. Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, Jiang B, Goodman MT, Sibug-Saber M, Cozen W, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol 2011, 29:4294–4301.
20. Zhu X, Wu J, Shan W, Zhou Z, Liu M, Huang Y. Sub-50 nm nanoparticles with biomimetic surfaces to sequentially overcome the mucosal diffusion barrier and the epithelial absorption barrier. Adv Funct Mater 2016, 26:2728–2738.
9. Whang SN, Filippova M, Duerksen-Hughes P. Recent progress in therapeutic treatments and screening strategies for the prevention and treatment of HPVassociated head and neck cancer. Viruses 2015, 7:5040–5065.
21. Zhu X, Wu J, Shan W, Tao W, Zhao L, Lim JM, D’Ortenzio M, Karnik R, Huang Y, Shi J. Polymeric nanoparticles amenable to simultaneous installation of exterior targeting and interior therapeutic proteins. Angew Chem Int Ed 2016, 55:3309–3312.
10. Haughey BH, Sinha P. Prognostic factors and survival unique to surgically treated p16+ oropharyngeal cancer. Laryngoscope 2012, 122:S13–S33.
22. Yu M, Wu J, Shi J, Farokhzad OC. Nanotechnology for protein delivery: overview and perspectives. J Control Release 2015, 240:24–37.
11. Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, Westra WH, Chung CH, Jordan RC, Lu C, et al. Human papollomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 2010, 363:24–35.
23. Wen Y, Meng WS. Recent in vivo evidences of particle-based delivery of small-interfering RNA (siRNA) into solid tumors. J Pharm Innov 2014, 9:158–173.
12. Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 2010, 17:1471–1474.
24. Sasidharan A, Monteiro-Riviere NA. Biomedical applications of gold nanomaterials: opportunities and challenges. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2015, 7:779–796.
13. Caster JM, Sethi M, Kowalczyk S, Wang E, Tian X, Nabeel Hyder S, Wagner KT, Zhang YA, Kapadia C, Man Au K, et al. Nanoparticle delivery of chemosensitizers improve chemotherapy efficacy without incurring additional toxicity. Nanoscale 2015, 7:2805–2811.
25. Liao W, Lai T, Chen L, Fu J, Sreenivasan ST, Yu Z, Ren J. Synthesis and characterization of a walnut peptides–zinc complex and its antiproliferative activity against human breast carcinoma cells through the induction of apoptosis. J Agric Food Chem 2016, 64:1509–1519.
14. Chu KS, Schorzman AN, Finniss MC, Bowerman CJ, Peng L, Luft JC, Madden AJ, Wang AZ,
26. Fang T, Dong Y, Zhang X, Xie K, Lin L, Wang H. Integrating a novel SN38 prodrug into the PEGylated
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© 2017 Wiley Periodicals, Inc.
WIREs Nanomedicine and Nanobiotechnology
Targeted nanoparticle for head and neck cancers
liposomal system as a robust platform for efficient cancer therapy in solid tumors. Int J Pharm 2016, 512:39–48. 27. Wu J, Kamaly N, Shi J, Zhao L, Xiao Z, Hollett G, John R, Ray S, Xu X, Zhang X, et al. Development of multinuclear polymeric nanoparticles as robust protein nanocarriers. Angew Chem Int Ed 2014, 53: 8975–8979. 28. Wu J, Zhao L, Xu X, Bertrand N, Choi WI, Yameen B, Shi J, Shah V, Mulvale M, MacLean JL, et al. Hydrophobic cysteine poly(disulfide)-based redox-hypersensitive nanoparticle platform for cancer theranostics. Angew Chem Int Ed Engl 2015, 54:9218–9223. 29. Zhao H, Lin ZY, Yildirimer L, Dhinakar A, Zhao X, Wu J. Polymer-based nanoparticles for protein delivery: design, strategies and applications. J Mater Chem B 2016, 4:4060–4071. 30. Xu X-D, Cheng Y-J, Wu J, Cheng H, Cheng S-X, Zhuo R-X, Zhang X-Z. Smart and hyper-fast responsive polyprodrug nanoplatform for targeted cancer therapy. Biomaterials 2016, 76:238–249. 31. Tao W, Zeng X, Wu J, Zhu X, Yu X, Zhang X, Zhang J, Liu G, Mei L. Polydopamine-based surface modification of novel nanoparticle-aptamer bioconjugates for in vivo breast cancer targeting and enhanced therapeutic effects. Theranostics 2016, 6:470. 32. Ling X, Huang Z, Wang J, Xie J, Feng M, Chen Y, Abbas F, Tu J, Wu J, Sun C. Development of an itraconazole encapsulated polymeric nanoparticle platform for effective antifungal therapy. J Mater Chem B 2016, 4:1787–1796. 33. Chen F, Wu J, Zheng C, Zhu J, Zhang Y, Cai F, Shah V, Liu J, Ge L, You X. TPGS modified reduced bovine serum albumin nanopariticles as a lipophilic anticancer drug carrier for overcoming multidrug resistance. J Mater Chem B 2016, 4:3959–3968. 34. Huang DY, Hou YL, Yang SM, Wang RG. Advances in nanomedicine for head and neck cancer. Front Biosci (Landmark Ed) 2014, 19:783–788. 35. Gu FX, Karnik R, Wang AZ, Alexis F, LevyNissenbaum E, Hong S, Langer RS, Farokhzad OC. Targeted nanoparticles for cancer therapy. Nano Today 2007, 2:14–21. 36. Wu J, Zhao X, Wu D, Chu C-C. Development of a biocompatible and biodegradable hybrid hydrogel platform for sustained release of ionic drugs. J Mater Chem B 2014, 2:6660–6668. 37. You X, Kang Y, Hollett G, Chen X, Zhao W, Gu Z, Wu J. Polymeric nanoparticles for colon cancer therapy: overview and perspectives. J Mater Chem B 2016, 4:7779–7792. 38. Hu X, Gong X. A new route to fabricate biocompatible hydrogels with controlled drug delivery behavior. J Colloid Interface Sci 2016, 470:62–70.
39. Wang J, Wang H, Li J, Liu Z, Xie H, Wei X, Lu D, Zhuang R, Xu X, Zheng S. iRGD-decorated polymeric nanoparticles for the efficient delivery of vandetanib to hepatocellular carcinoma: preparation and in vitro and in vivo evaluation. ACS Appl Mater Interfaces 2016, 8:19228–19237. 40. Wang H, Xie H, Wu J, Wei X, Zhou L, Xu X, Zheng S. Structure-based rational design of prodrugs to enable their combination with polymeric nanoparticle delivery platforms for enhanced antitumor efficacy. Angew Chem 2014, 126:11716–11721. 41. Caponigro F, Di Gennaro E, Ionna F, Longo F, Aversa C, Pavone E, Maglione MG, Di Marzo M, Muto P, Cavalcanti E, et al. Phase II clinical study of valproic acid plus cisplatin and cetuximab in recurrent and/or metastatic squamous cell carcinoma of head and neck-V-chance trial. BMC Cancer 2016, 16:918. 42. Forastiere AA, Metch B, Schuller DE, Ensley JF, Hutchins LF, Triozzi P, Kish JA, McClure S, VonFeldt E, Williamson SK, et al. Randomized comparison of cisplatin plus fluorouracil and carboplatin plus fluorouracil versus methotrexate in advanced squamous-cell carcinoma of the head and neck: a southwest oncology group study. J Clin Oncol 1992, 10:1245–1251. 43. Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB, Kish JA, Kim HE, Cmelak AJ, Rotman M, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 2004, 350:1937–1944. 44. Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefèbvre J-L, Greiner RH, Giralt J, Maingon P, Rolland F, Bolla M, et al. Postoperative irradiation with or without concominant chemotherapy for locally advanced head and neck cancer. N Engl J Med 2004, 350:1945–1952. 45. Chow EK-H, Ho D. Cancer nanomedicine: from drug delivery to imaging. Sci Transl Med 2013, 5:216rv214. 46. Ferrari M. Cancer nanotechnology: opportunities and challenges. Nat Rev Cancer 2005, 5:161–171. 47. Cheng L, Wang C, Feng L, Yang K, Liu Z. Functional nanomaterials for phototherapies of cancer. Chem Rev 2014, 114:10869–10939. 48. Hubbell JA, Chilkoti A. Nanomaterials for drug delivery. Science 2012, 337:303–305. 49. Li Y, Huang Y, Wang Z, Carniato F, Xie Y, Patterson JP, Thompson MP, Andolina CM, Ditri TB, Millstone JE, et al. Polycatechol nanoparticle MRI contrast agents. Small 2016, 12:668–677. 50. Di Corato R, Bigall NC, Ragusa A, Dorfs D, Genovese A, Marotta R, Manna L, Pellegrino T. Multifunctional nanobeads based on quantum dots and magnetic nanoparticles: synthesis and cancer cell targeting and sorting. ACS Nano 2011, 5:1109–1121.
© 2017 Wiley Periodicals, Inc.
11 of 13
Overview
wires.wiley.com/nanomed
51. Yu MK, Park J, Jon S. Targeting strategies for multifunctional nanoparticles in cancer imaging and therapy. Theranostics 2012, 2:3. 52. Eustis S, el-Sayed MA. Why gold nanoparticles are more precious than pretty gold: noble metal surface plasmon resonance and its enhancement of the radiative and nonradiative properties of nanocrystals of different shapes. Chem Soc Rev 2006, 35:209–217. 53. Huang X, Jain PK, El-Sayed IH, El-Sayed MA. Gold nanoparticles: interesting optical properties and recent applications in cancer diagnostics and therapy. Nanomedicine (Lond) 2007, 2:681–693. 54. El-Sayed IH, Huang XH, El-Sayed MA. Surface plasmon resonance scattering and absorption of antiEGFR antibody conjugated gold nanoparticles in cancer diagnostics: applications in oral cancer. Nano Lett 2005, 5:829–834.
63. Wang D, Fei B, Halig LV, Qin X, Hu Z, Xu H, Wang YA, Chen Z, Kim S, Shin DM, et al. Targeted iron-oxide nanoparticle for photodynamic therapy and imaging of head and neck cancer. ACS Nano 2014, 8:6620–6632. 64. Brown MS, Diallo OT, Hu M, Ehsanian R, Yang X, Arun P, Lu H, Korman V, Unger G, Ahmed K, et al. CK2 modulation of NF-kappaB, TP53, and the malignant phenotype in head and neck cancer by antiCK2 oligonucleotides in vitro or in vivo via sub-50-nm nanocapsules. Clin Cancer Res 2010, 16:2295–2307. 65. Arany S, Benoit DS, Dewhurst S, Ovitt CE. Nanoparticle-mediated gene silencing confers radioprotection to salivary glands in vivo. Mol Ther 2013, 21: 1182–1194.
55. Kang B, Austin LA, El-Sayed MA. Real-time molecular imaging throughout the entire cell cycle by targeted plasmonic-enhanced Rayleigh/Raman spectroscopy. Nano Lett 2012, 12:5369–5375.
66. Colley HE, Hearnden V, Avila-Olias M, Cecchin D, Canton I, Madsen J, MacNeil S, Warren N, Hu K, McKeating JA, et al. Polymersome-mediated delivery of combination anticancer therapy to head and neck cancer cells: 2D and 3D in vitro evaluation. Mol Pharm 2014, 11:1176–1188.
56. Trinidad AJ, Hong SJ, Peng Q, Madsen SJ, Hirschberg H. Combined concurrent photodynamic and gold nanoshell loaded macrophage-mediated photothermal therapies: an in vitro study on squamous cell head and neck carcinoma. Lasers Surg Med 2014, 46:310–318.
67. Wang X, Shi L, Tu Q, Wang H, Zhang H, Wang P, Zhang L, Huang Z, Zhao F, Luan H, et al. Treating cutaneous squamous cell carcinoma using 5aminolevulinic acid polylactic-co-glycolic acid nanoparticle-mediated photodynamic therapy in a mouse model. Int J Nanomedicine 2015, 10:347–355.
57. Huang XH, El-Sayed IH, Qian W, El-Sayed MA. Cancer cell imaging and photothermal therapy in the nearinfrared region by using gold nanorods. J Am Chem Soc 2006, 128:2115–2120.
68. Chang RS, Suh MS, Kim S, Shim G, Lee S, Han SS, Lee KE, Jeon H, Choi H-G, Choi Y, et al. Cationic drug-derived nanoparticles for multifunctional delivery of anticancer siRNA. Biomaterials 2011, 32:9785–9795.
58. Sano D, Berlin JM, Pham TT, Marcano DC, Valdecanas DR, Zhou G, Milas L, Myers JN, Tour JM. Noncovalent assembly of targeted carbon nanovectors enables synergistic drug and radiation cancer therapy in vivo. ACS Nano 2012, 6: 2497–2505. 59. Berlin JM, Pham TT, Sano D, Mohamedali KA, Marcano DC, Myers JN, Tour JM. Noncovalent functionalization of carbon nanovectors with an antibody enables targeted drug delivery. ACS Nano 2011, 5:6643–6650. 60. Bhirde AA, Patel V, Gavard J, Zhang G, Sousa AA, Masedunskas A, Leapman RD, Weigert R, Gutkind JS, Rusling JF. Targeted killing of cancer cells in vivo and in vitro with EGF-directed carbon nanotube-based drug delivery. ACS Nano 2009, 3:307–316.
69. Yu YH, Kim E, Park DE, Shim G, Lee S, Kim YB, Kim C-W, Oh Y-K. Cationic solid lipid nanoparticles for co-delivery of paclitaxel and siRNA. Eur J Pharm Biopharm 2012, 80:268–273. 70. Piao L, Zhang M, Datta J, Xie X, Su T, Li H, Teknos TN, Pan Q. Lipid-based nanoparticle delivery of Pre-miR-107 inhibits the tumorigenicity of head and neck squamous cell carcinoma. Mol Ther 2012, 20:1261–1269. 71. Li Y, Xie Y, Wang Z, Zang N, Carniato F, Huang Y, Andolina CM, Parent LR, Ditri TB, Walter ED, et al. Structure and Function of Iron-Loaded Synthetic Melanin. ACS Nano 2016, 10:10186–10194. 72. Banik BL, Fattahi P, Brown JL. Polymeric nanoparticles: the future of nanomedicine. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2016, 8:271–299.
61. Zhao Q, Wang L, Cheng R, Mao L, Arnold RD, Howerth EW, Chen ZG, Platt S. Magnetic nanoparticle-based hyperthermia for head & neck cancer in mouse models. Theranostics 2012, 2:113–121.
73. Feyzizarnagh H, Yoon DY, Goltz M, Kim DS. Peptide nanostructures in biomedical technology. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2016, 8:730–743.
62. Xie M, Zhang H, Xu Y, Liu T, Chen S, Wang J, Zhang T. Expression of folate receptors in nasopharyngeal and laryngeal carcinoma and folate receptormediated endocytosis by molecular targeted nanomedicine. Int J Nanomedicine 2013, 8:2443–2451.
74. Frank LA, Contri RV, Beck RC, Pohlmann AR, Guterres SS. Improving drug biological effects by encapsulation into polymeric nanocapsules. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2015, 7:623–639.
12 of 13
© 2017 Wiley Periodicals, Inc.
WIREs Nanomedicine and Nanobiotechnology
Targeted nanoparticle for head and neck cancers
75. Rait AS, Pirollo KF, Ulick D, Cullen K, Chang EH. HER-2-targeted antisense oligonucleotide results in sensitization of head and neck cancer cells to chemotherapeutic agents. Ann N Y Acad Sci 2003, 1002:78–89. 76. Shim G, Han S-E, Yu Y-H, Lee S, Lee HY, Kim K, Kwon IC, Park TG, Kim YB, Choi YS, et al. Trilysinoyl oleylamide-based cationic liposomes for systemic co-delivery of siRNA and an anticancer drug. J Control Release 2011, 155:60–66. 77. Ward BB, Dunham T, Majoros IJ, Baker JR Jr. Targeted dendrimer chemotherapy in an animal model for head and neck squamous cell carcinoma. J Oral Maxillofac Surg 2011, 69:2452–2459. 78. Dosio F, Arpicco S, Stella B, Brusa P, Cattel L. Folatemediated targeting of albumin conjugates of paclitaxel obtained through a heterogeneous phase system. Int J Pharm 2009, 382:117–123. 79. Gao Z, Zhang L, Sun Y. Nanotechnology applied to overcome tumor drug resistance. J Control Release 2012, 162:45–55. 80. Kamaly N, Xiao Z, Valencia PM, RadovicMoreno AF, Farokhzad OC. Targeted polymeric therapeutic nanoparticles: design, development and clinical translation. Chem Soc Rev 2012, 41:2971–3010. 81. Byrne JD, Betancourt T, Brannon-Peppas L. Active targeting schemes for nanoparticle systems in cancer therapeutics. Adv Drug Deliv Rev 2008, 60:1615–1626. 82. Ang KK, Berkey BA, Tu XY, Zhang HZ, Katz R, Hammond EH, Fu KK, Milas L. Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma. Cancer Res 2002, 62:7350–7356. 83. He YK, Zeng Q, Drenning SD, Melhem MF, Tweardy DJ, Huang L, Grandis JR. Inhibition of human squamous cell carcinoma growth in vivo by epidermal growth factor receptor antisense RNA transcribed from the U6 promoter. J Natl Cancer Inst 1998, 90:1080–1087. 84. Cho H-J, Chong S, Chung S-J, Shim C-K, Kim D-D. Poly-L-arginine and dextran sulfate-based nanocomplex for epidermal growth factor receptor (EGFR) siRNA delivery: its application for head and neck cancer treatment. Pharm Res 2012, 29:1007–1019. 85. Elnakat H, Ratnam M. Distribution, functionality and gene regulation of folate receptor isoforms: implications in targeted therapy. Adv Drug Deliv Rev 2004, 56:1067–1084. 86. Leamon CP, Reddy JA. Folate-targeted chemotherapy. Adv Drug Deliv Rev 2004, 56:1127–1141. 87. Tibbitt MW, Dahlman JE, Langer R. Emerging frontiers in drug delivery. J Am Chem Soc 2016, 138:704–717. 88. Miyagi Y, Fujiwara K, Kigawa J, Itamochi H, Nagao S, Aotani E, Terakawa N, Kohno I. Sankai
Gynecology Study G. Intraperitoneal carboplatin infusion may be a pharmacologically more reasonable route than intravenous administration as a systemic chemotherapy. A comparative pharmacokinetic analysis of platinum using a new mathematical model after intraperitoneal vs. intravenous infusion of carboplatin--a Sankai Gynecology Study Group (SGSG) study. Gynecol Oncol 2005, 99:591–596. 89. Yen MS, Juang CM, Lai CR, Chao GC, Ng HT, Yuan CC. Intraperitoneal cisplatin-based chemotherapy vs intravenous cisplatin-based chemotherapy for stage III optimally cytoreduced epithelial ovarian cancer. Int J Gynecol Obstet 2001, 72:55–60. 90. Bristow RE, Santillan A, Salani R, Diaz-Montes TP, Giuntoli RL 2nd, Meisner BC, Armstrong DK, Frick KD. Intraperitoneal cisplatin and paclitaxel versus intravenous carboplatin and paclitaxel chemotherapy for Stage III ovarian cancer: a cost-effectiveness analysis. Gynecol Oncol 2007, 106:476–481. 91. Zhao H, Feng H, Liu DJ, Liu J, Ji N, Chen FM, Luo XB, Zhou Y, Dan HX, Zeng X, et al. Selfassembling monomeric nucleoside molecular nanoparticles loaded with 5-fu enhancing therapeutic efficacy against oral cancer. ACS Nano 2015, 9:9638–9651. 92. Wolinsky JB, Colson YL, Grinstaff MW. Local drug delivery strategies for cancer treatment: gels, nanoparticles, polymeric films, rods, and wafers. J Control Release 2012, 159:14–26. 93. Chang RS, Suh MS, Kim S, Shim G, Lee S, Han SS, Lee KE, Jeon H, Choi HG, Choi Y, et al. Cationic drugderived nanoparticles for multifunctional delivery of anticancer siRNA. Biomaterials 2011, 32:9785–9795. 94. Robert D, SULLIVAN EM, Marguerite P. SIKES. Antimetabolite–metabolite combination cancer chemotherapy. Cancer 1959, 12:1248–1262. 95. Robbins KT, Storniolo AM, Kerber C, Seagren S, Berson A, Howell SB. Rapid superselective high-dose cisplatin infusion for advanced head and neck malignancies. Head Neck 1992, 14:364–371. 96. Wolpert SM, Kwan ES, Heros D, Kasdon DL, Hedges TR 3rd.. Selective delivery of chemotherapeutic agents with a new catheter system. Radiology 1988, 166:547–549. 97. Homma A, Onimaru R, Matsuura K, Robbins KT, Fujii M. Intra-arterial chemoradiotherapy for head and neck cancer. Jpn J Clin Oncol 2016, 46:4–12. 98. Damascelli B, Patelli G, Ticha V, Di Tolla G, Frigerio LF, Garbagnati F, Lanocita R, Marchiano A, Spreafico C, Mattavelli F, et al. Feasibility and efficacy of percutaneous transcatheter intraarterial chemotherapy with paclitaxel in albumin nanoparticles for advanced squamous-cell carcinoma of the oral cavity, oropharynx, and hypopharynx. J Vasc Interv Radiol 2007, 18:1395–1403.
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