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Electronic Supplementary Material (ESI) for Journal of Materials Chemistry B. This journal is © The Royal Society of Chemistry 2015

Electronic Supplementary Information, Fine-tuning thermoresponsive functional poly(εcaprolactone)s to enhance micelle stability and drug loading Elizabeth A. Rainbolt, Jason B. Miller, Katherine E. Washington, Suchithra A. Senevirathne, Michael C. Biewer, Daniel J. Siegwart, and Mihaela C. Stefan

O

O

O

O

O

Sn(Oct)2 Toluene, 

O

O O

HO O

O

x O

5.11 ppm

O H y

O

4.06 ppm

4.17 ppm

4.17 4.05

Short File Name: PMECL-co-PCL.esp

Normalized Intensity

5.11

2.0

1.5

60 min

1.0

30 min

0.5

20 min

0

5 min 7.5

7.0

6.5

6.0

5.5

5.0

4.5 4.0 3.5 Chemical Shift (ppm)

3.0

2.5

2.0

1.5

1.0

0.5

Fig. S1. Copolymerization of ME1CL and CL: 1H NMR spectra at different time points in the reaction revealed the incorporation of ME1CL and CL relative to BnO chain end. Integration of the labeled peaks is shown below in Table S1. Table S1. Summary of PME1CL-co-PCL δ (ppm) Time (min)

5.11 (BnO)

4.17 (ME1CL)

4.06 (CL)

5

1.0

2.7

3.6

20

1.0

15.9

15.5

30

1.0

25.5

25.5

60

1.0

33.9

35.7

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7.5

7.0

6.5

6.0

5.5 5.0

0.2

5.0 4.5 4.0 3.5 Chemical Shift (ppm)

0

4.5 4.0 3.5 Chemical Shift (ppm)

2.39 2.38 2.32 2.30 1.85 2.29 1.84 1.83 1.65 1.81 1.39 1.80 1.38 1.78

5.5 3.0

3.0 2.5

2.5

2.0

2.0

0.340

4.16

2.39 2.32 1.84 2.30 1.83 2.29 1.82 1.80 1.64 1.79 1.54 1.78 1.39 1.38

0.2

4.329 0.678

1.976 0.338

12.435 2.888

0

1.955 0.222 0.083 4.166 0.126 0.558 0.216

0.7 3.37

6.0 4.06 4.04

3.54

3.63

0.6

3.36

Short File Name: P2.esp 3.64

6.5 2.006 0.336

7.26

3.37

0.7

2.784

0.5 3.59

7.0

3.54

7.5

4.16

5.11

0.1

4.07 4.06 3.74

0.017

0.3

12.164

0.1

5.11

Normalized Intensity

0.4

1.999 0.227

0.014

0.3 7.26

Normalized Intensity

3.64

Short File Name: P1.esp

1.0

0.9

0.8

0.5

1.5

Fig. S2. 1H NMR spectrum of P1.

1.0

0.9

0.8

0.6

0.4

1.5

1.0 0.5 0

1.0

0.5

0

Fig. S3. 1H NMR spectrum of P2.

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7.5

7.0

6.5

6.0

5.5

5.0

4.5 4.0 3.5 Chemical Shift (ppm) 3.0

3.0 2.5

2.5

2.0

2.0

0.442

4.5 4.0 3.5 Chemical Shift (ppm)

4.760 0.874

0.2 0.126

4.107 0.394

2.022 0.135

2.947

10.090

1.65 1.38

2.40 2.38 1.85 1.84 1.83 1.81 1.80 1.79

3.50 3.54

4.17 4.16 3.59 3.36

0.7

2.40 2.39 2.31 1.87 1.83 1.82 1.80 1.79 1.38 1.59

Short File Name: P4.esp 3.36

0

2.42

0.5 3.64

5.0 4.05

5.11 5.09

3.37

0.8

2.097 0.392

0.4 3.37

5.5

3.50

6.0

3.65

6.5 2.002 0.138

0.011

7.26

Normalized Intensity

0.6

8.281 3.058

0.9 7.0

4.07

7.5

4.17 4.16

4.19

0.1

5.11

7.35

0.1

7.26

0.3

2.009 0.389

0.029

Normalized Intensity

3.64

Short File Name: P3.esp

1.0

0.9

0.5

0.4

0.2

1.5

1.5

1.0

1.0

0.5 0

Fig. S4. 1H NMR spectrum of P3.

1.0

0.8

0.7

0.6

0.3

0

0.5

Fig. S5. 1H NMR spectrum of P4.

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Fig. S6 Size exclusion chromatography (SEC / GPC) traces of copolymers P1 – P4.

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Fig. S7. DLS measurements: hydrodynamic diameters (Dh) of empty (blue, solid) and DOX-loaded (red, dashed) micelles of P1 – P4.

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EMPTY

DOX

P1

P3

Fig. S8. TEM images of P1 and P3 empty micelles (left); and P1DOX and P3DOX (right); micelles deposited on copper mesh grid and stained with phosphotungstic acid; scale bars 200 nm.

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20x

40x

Fig. S9. Digital fluorescence microscopy showing the uptake of DOX-loaded micelles P3DOX: left, DOX shown in red; center, DAPI-stained cell nuclei in blue; right, overlay of red and blue channels; scale bars signify 100 μm.

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