ChinaNanomedicine 2016 / Nanomedicine: Nanotechnology, Biology, and Medicine 14 (2018) 1743–1885
Tumor microenvironment-responsive intelligent nanocomposites for efficient theranostics of glioma Heng Liua,b, Gang Liub,*, Weiguo Zhanga,c,*, aDepartment Of Radiology, Institute Of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China, bState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China, cChongqing Clinical Research Center for Imaging and Nuclear Medicine, Chongqing, China ⁎Corresponding authors. E-mail addresses:
[email protected] (G. Liu),
[email protected] (W. Zhang) The tumor microenvironment (TME) of malignant glioma is characterized by hypoxia and acidification, which jointly contribute to tumor angiogenesis, invasion, metastasis and treatment resistance.1 Approaches for improving tumor oxygenation are of great importance for enhancing oxygen-involved radiation response in cancer treatment. In the present study, multifunctional AuNCsMnO2-SubMBs nanocomposites with good stability and biocompatibility are successfully fabricated via layer-by-layer approach (see scheme), and focused ultrasound mediated blood-brain barrier opening2 allows the efficient delivery of nanocomposites to the brain tumor region. The high reactivity of MnO2 towards endogenous reduced glutathione (GSH) and hydrogen peroxide (H2O2) within the TME can realize TME-responsive MR imaging and CT/NIRF imaging. The produced O2 at tumor site in situ can effectively alleviate tumor hypoxia, decrease acidification and inhibit tumor angiogenesis. Moreover, O2 and AuNCs as radiotherapy sensitizers3 together can greatly improve the radiotherapy efficiency. The developed AuNCs-MnO2-SubMBs will open up new avenues for construction of intelligent nanoplatforms with comprehensive TME regulation ability and developing more precise and efficient theranostics against hypoxic solid tumors.
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The water-soluble fullerene-based materials have attracted considerable attentions as the new generation of theranostic agents in nanomedicine. In the preceding work of our project group, the water-soluble C60(NCH2COONa)13 nanoparticles were prepared by nitrene chemistry.1 In the present work, the nanoparticles were used to determine the effect of scavenging free radicals by spectrophotometry described in the literature.2 In addition, the fluorescence property of C60(NCH2COONa)13 was also investigated by fluorosepctrophotometry. Figure 1, A showed the correlations between the clearance of ABTS+• In vitro and the contents of C60(NCH2COONa)13. The inhibition percentage of ABTS+• was increased from 15.8% to 93.0% when 11.1-155.6 μg/mL C60(NCH2COONa)13 was added. The change of the inhibition percentage correlated to the concentrations was fitted by a three-parameter single exponential function of the non-linear curve analysis. IC50 value of C60(NCH2COONa)13, defined as the concentration of 50% inhibition percentage, was calculated to 49.4 μg/mL. In addition, C60(NCH2COONa)13 can also scavenge DPPH• radicals in a dose-dependent manner, whose maximal inhibition percentage of DPPH• (30.2%) was found at around 167 μg/mL. It has been reported that DPPH• and ABTS+• may be scavenged via donation of hydrogen atom (H•) and via an electron (e) transfer reaction, respectively.2 It suggested that C60(NCH2COONa)13 more easily exerted radical-scavenging action via donating electron (e) than donating H•. The clearance of ABTS+• and DPPH• In vitro can be used to demonstrate the ability of C60(NCH2COONa)13 to scavenge ROS in biological systems in vivo, making it ideal candidate as an antioxidant for ROS related disease. The excitation and emission spectra of C60(NCH2COONa)13 in aqueous solution were showed in Figure 1, B, in which the excitation peak and emission peak were at about 460 nm and 540 nm, respectively. Although the exact mechanism for the fluorescence generation of C60(NCH2COONa)13 is, as yet, an unanswered question, the preliminary result indicated that the water-soluble glycine derivatives of fullerene have potential applications as fluorescent nanoprobes by label-free strategy.3 Based on the discussion above, it revealed that C60(NCH2COONa)13 will be an ideal candidate as a novel fullerene-based theranostic agents in nanomedicine.1
Figure 1. The percentage inhibition of ABTS+• treated by C60(NCH2COONa)13 (A), excitation and emission spectra of C60(NCH2COONa)13 (B).
Figure. Schematic illustration of the construction of multifunctional AuNCs-MnO2-SubMBs nanocomposites and their application for efficient theranostics of glioma.
References 1. Chen Q, et al. Intelligent albumin-MnO2 nanoparticles as pH-/H2O2-responsive dissociable nanocarriers to modulate tumor hypoxia for effective combination therapy. Adv Mater 2016. https://doi.org/10.1002/adma.201601902. 2. Lammers T, et al. Theranostic USPIO-loaded microbubbles for mediating and monitoring blood-brain barrier permeation. Adv Funct Mater 2015, 25:36-43. 3. Zhang XD, et al. Ultrasmall Au(10-12)(SG)(10-12) nanomolecules for high tumor specificity and cancer radiotherapy. Adv Mater 2014, 26:4565-4568.
References 1. Xiong FX, et al. Multi-additions of azides onto fullerenes: formation of water-soluble glycin C60 derivatives as potential reactive oxygen species scavengers. Nanomed-Nanotechnol 2016; 12(2):525-526. 2. Li XC, et al. Antioxidant activity and mechanism of Rhizoma cimicifugae. Chem Cent J 2012;6:140. 3. Zhen MM, et al. Multifunctional nanoprobe for MRI/optical dual-modality imaging and radical scavenging. Chem-Euro J 2013;19(43):14675-14681. 1 Supported by the Natural Science Foundation of China (Grant 21305027), the Public Welfare (Agriculture) Research Project of China (Grant 201303030), and the Key Project of Henan Educational Committee of China (Grant 16A210007).
https://doi.org/10.1016/j.nano.2017.11.088
https://doi.org/10.1016/j.nano.2017.11.089
Fullerene fluorescent balls as potential nanotheranostic agents Yikang Fana, Mingwu Qiaob, Yanjie Liua, Fengxia Xionga, Xiaojuan Maa, Fengming Yana, Hezhong Wanga, Rui Hea,*, aCollege of Plant Protection / NanoAgro Center, Henan Agricultural University, Zhengzhou 450002, China, bInstitute of Food Science and Technology, Henan Agricultural University, Zhengzhou 450002, China ⁎Corresponding author. E-mail address:
[email protected] (R. He)
Folate-modified annonaceous acetogenins (ACGs) nanosuspensions based on a self-assembly stabilizer for tumor targeting Jingyi Hong, Xiangtao Wang*, Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China ⁎Corresponding author. E-mail address:
[email protected] (X. Wang)
