Supporting Information
A Structure-Property Relationship Study of the
Well-defined Telodendrimers to improve
hemocompatibility of nanocarriers for anticancer
drug delivery
Changying Shi,†,1 Dekai Yuan, ¶,1, Shikha Nangia,‡ Gaofei Xu,†,¶ Kit S. Lam, § Juntao Luo, †*
†
Department of Pharmacology, SUNY Upstate Cancer Research Institute, State University of
New York Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA
¶
Department of Applied Chemistry, College of Science, China Agricultural University, Beijing,
100193, China
‡
Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY
13244, USA
§
Department of Biochemistry and Molecular Medicine, School of Medicine, University of
California Davis, Sacramento, CA 95817, USA
1
These authors have the same contribution to this study
* Corresponding author. Tel.: +1 315 464 7965; fax: +1 315 464 5143.
E-mail addresses: luoj@upstate.edu (J. Luo)
Supporting Information
A Structure-Property Relationship Study of the
Well-defined Telodendrimers to improve
hemocompatibility of nanocarriers for anticancer
drug delivery
Changying Shi,†,1 Dekai Yuan, ¶,1, Shikha Nangia,‡ Gaofei Xu,†,¶ Kit S. Lam, § Juntao Luo, †*
†
Department of Pharmacology, SUNY Upstate Cancer Research Institute, State University of
New York Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA
¶
Department of Applied Chemistry, College of Science, China Agricultural University, Beijing,
100193, China
‡
Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY
13244, USA
§
Department of Biochemistry and Molecular Medicine, School of Medicine, University of
California Davis, Sacramento, CA 95817, USA
1
These authors have the same contribution to this study
2
Some other chemodrugs, such as doxorubicin1, daunorubicin2, vincristin3, dexamethasone4, etc.
have been encapsulated in this nanocarrier and reported in our previous publications.
Preparation of t-Butyl Cholate (t-Butyl 3α, 7α, 12α-Trihydroxy-5β-cholan-24-ate) 1 5
Trifluoroacetic anhydride (100 mL, 45.07 mmol) was dropped into a stirred solution of cholic
acid (25.0g, 61.24 mmol) and anhydrous THF (400 mL) below 0°C. After the ice bath was
removed, the solution was stirred for 1.5 hrs at room temperature. Then the solution was cooled
down again, and dry t-BuOH (150 mL) was added below 0°C. After the solution was stirred for
7 hrs at room temperature, the first portion of aqueous NH3 (120 ml, 28%, w/w) was dropped
into the solution below 5°C and the solution was stirred for 12 hrs at 0~5°C. Then another
portion of aqueous NH3 (60 mL) was added into the solution. After 4 hrs at room temperature,
the mixture was partitioned between Et2O (800 mL) and water (200 mL). After washing with
aqueous NaOH (1 M, 800 mL), water (2×500 mL), the organic layer was dried with anhydrous
MgSO4. A foam was obtained after evaporation and a white solid of 1 27.5 g was obtained by
crystallization with acetonitrile (80 mL), yield 96.7 %, MS(m/z) [M+H]+: Cal.464.4, Found
465.5;
Preparation of t-Butyl (3α, 5β, 7α, 12α)-7,12-Dihydroxy-3-(oxyranylmethoxy)-cholan-24-ate 2 6
A solution of 1 (25 g, 53.84 mmol) in CH2Cl2 (15 mL) was added to a mixture of
epichlorohydrin (65 mL), aqueous NaOH (50%, w/w, 120 mL) and (n-Bu)4NOH·30 H2O (8.0g,
1mmol) with vigorous stirring below 20°C. Then, the mixture was stirred for another 16 hrs at
room temperature. Two products were verified by TLC method (Rf=0.4 and 0.6 in nhexane/ethyl acetate (1:1, v/v) system). After that, water (200 mL) was added into the mixture
and the organic layer was separated and dried by anhydrous MgSO4 overnight. After the solvent
evaporated, a pink yellow oil was obtained and purified by flash chromatography
(n-hexane/EtOAc, 4:1, 2:1 and 1:1, v/v). All the components with their Rf >0.4 were collected
together for the separation of 3. Compound 2 was obtained as a white foam (Rf=0.4 in nhexane/ethyl acetate 1:1, v/v), 12.5g, yield 44.7%, HRMS (m/z) calcd. for C31H52O6 (M+H)+:
Cal.521.3837, Found 521.3839, 1HNMR (CDCl3, 600 MHz,) δ: 0.68 (s, 1 H), 0.88 (s ,3 H, CH3),
0.97 (d, J= 6.6 Hz, 3 H,CH3), 1.15~2.23 (m, 23 H,), 1.43 (s, 9 H, tertiary butyl), 2.60 (m, 1 H),
3
2.78 (t, J= 4.8 Hz, 1 H ), 3.12 (s, 1 H), 3.18 (s, 1 H), 3.46 (m, 1 H) , 3.69 (m, 1 H, OH), 3.83 (s, 1
H), 3.97 (s, 1 H). ), ;
Preparation of t-Butyl (3α, 5β, 7α, 12α)-12-Dihydroxy-3,7-di(oxyranylmethoxy)-cholan-24-ate
or t-Butyl (3α, 5β, 7α, 12α)-7-Dihydroxy-3,12-di(oxyranylmethoxy)-cholan-24-ate 3
The collection in step 1.2 was separated by flash matography (n-hexane/EtOAc, 4:1, 2:1 and 1:1,
v/v), and compound 3 was obtained as yellow jelly, 4.5g, yield 14.5%, HRMS(m/z) calcd. for
C34H56O7 (M+NH4)+: Cal.594.4364, Found 594.4375, 1HNMR (CDCl3, 600 MHz,) δ: 0.67 (d s,
1 H,), 0.88 (s, 3 H,), 0.96 (d, J= 6.6 Hz, 3 H,), 1.15~2.23 (m, 23 H,), 1.43 (s, 9 H, tertiary butyl),
2.59 (m, 2 H), 2.78 (m, J= 4.2 Hz, 2 H), 3.12 (s, 2 H), 3.17 (m, 2 H), 3.38~3.52 (m, 4 H), 3.81 (s,
1 H), 3.93 (s, 1 H)..
Preparation of (3α, 5β, 7α, 12α)-7,12-Dihydroxy-3-(2,3-dihydroxy-1-propoxy)-cholic acid 4
CF3COOH (25 mL) was dropped into the solution of 2 (1.6 g, 3.07mmol) in CH2Cl2 (25 mL)
below 0°C under stirring. The mixture was stirred for another 1.5 hrs at room temperature. TLC
(n-hexane/EtOAc, 1:1, v/v) test proved that the reaction went to completion. After the solvents
were removed by air blowing, a yellow jelly was obtained. LiOH (0.7g, 10 eq.) aqueous solution
(20mL) was added into the flask. The residue disappeared gradually and a pink yellow solution
was obtained. After stirring at room temperature for 16 hrs, the solution was cooled below 5°C
and condensed HCl was dropped into the solution. Compound 4 precipitated out as a white
solid, and the TLC test proved that the product had high purity and could be used in the next step
without further purification. After freeze drying, 4 (1.25 g) was obtained, yield 84.4%,
HRMS(m/z) calcd. for C27H46O7 (M+H)+: Cal. 483.3317, Found 483.3315, 1HNMR (DMSOd6,600 MHz) δ: 0.60 (s, 3 H,), 0.82 (s, 3 H,), 0.96 (d, J= 6.6 Hz, 3 H,), 1.15~2.24 (m, 23 H,),
2.59 (m, 2 H,), 2.67 (m, 1 H,), 2.76 (s, 1 H,), 3.02 (m, 1 H,), 3.20 (m, 1 H,), 3.50 (m, 1 H,), 3.61
(s, 1 H,), 3.74 (s, 1 H,), 3.79 (s, 1 H,), 4.03 (m, 2 H,), 4.14 (s, 1 H,), 5.58 (ds, 1 H,,). ;
Preparation of (3α, 5β, 7α, 12α)-12-Dihydroxy-3,7-di(2,3-dihydroxy-1-propoxy)-cholic acid or t
(3α, 5β, 7α, 12α)-7-Dihydroxy-3,12-di(2,3-dihydroxy-1-propoxy)-cholic acid 5
TFA (30 mL) was dropped into the solution of Compound 3 (3.5 g, 6.01mmol) in CH2Cl2 (30
mL) below 0°C with stirring. The mixture was stirred for another 2.5 hrs at room temperature.
4
After the solvents were removed by air blowing, a yellow jelly was obtained. LiOH (2.0g, 20
eq.) aqueous solution (25 mL) was added into the flask. The residue disappeared gradually and a
pink yellow solution was obtained. After stirring at room temperature for 16 hrs, the solution
was cooled below 5°C and condensed HCl was dropped into the solution. The product was
extracted by 3×100 mL ethyl acetate and the organic layer was dried with anhydrous Na2SO4.
After being purified by flash chromatography (CH2Cl2:CH3OH= 5:1, 3:1, v/v), compound 5 was
obtained as pink yellow jelly, 1.22 g, yield 36.5%, HRMS(m/z) calcd. for C30H52O9 (M+H)+:
Cal. 557.3684, Found 557.3682, 1HNMR (DMSO-d6, 600 MHz,) δ: 0.58~0.62 (ds, 3 H,), 0.83
(s, 3 H,), 0.87~ 0.92 (m, 3 H,), 1.17~2.25 (m, 23 H,), 2.46 (s, 1 H,), 2.50 (m, 3 H,), 3.00 (m, 2
H,), 3.16 (m, 4 H,), 3.27 (m, 2 H,), 3.50 (m, 4 H,), 3.77 (s, 1 H,), 4.46 (s, 2 H,), 4.56 (s, 1 H,). ;
Preparation of t-Butyl (3α, 5β, 7α, 12α)-7, 12-Dihydroxy-3-(3-amino-2-hydroxy-1-propoxy)cholan-24-ate 6
Compound 2 (6.5 g, 12.49mmol) was dissolved into NH3 methanol solution (7M, 150 mL)
containing LiCl (0.4g, mmol, eq.) in a sealed flask and stirred at room temperature for 24 hrs.
TLC test (Rf=0.3, CH2Cl2: MeOH: NH3·H2O (25%) = 10:1:0.1, v/v/v) proved that the reaction
was completed. After being purified by flash matography (CH2Cl2: MeOH:NH3·H2O (25%) =
10:1:0.1, v/v/v), compound 6 was obtained as white foam, 6.2 g, yield 92.4%, HRMS (m/z)
calcd. for C31H55NO6 (M+H)+: Cal. 538.4102, Found 538.4099, 1HNMR(, CDCl3, 600 MHz) δ:
0.67 (s, 3 H,), 0.88 (s, 3 H,), 0.97 (d, J= 6.6 Hz, 3 H,), 1.12~2.29 (m, 23 H,), 1.43 (s, 9H, tertiary
butyl), 2.64 (s, 3 H,), 2.75 (m, 2 H,), 2.83 (m, 1 H,), 3.12 (m, 1 H,), 3.43 (m, 1 H,), 3.50 (m, 1
H,), 3.76 (s, 1 H,), 3.83 (s, 1 H,), 3.95 (s, 1 H,) .
Preparation of t-Butyl (3α, 5β, 7α, 12α)-7, 12-Dihydroxy-3-(3-Fmocamino-2-hydroxy-1propoxy)-cholan-24-ate 7
Compound 6 (3.0 g, 5.58mmol), Fmoc-OSu (3.0 g, 8.90 mmol) and DIEA (1.5 g, 11.61mmol,)
were dissolved into CH2Cl2 (100 mL) with stirring at room temperature for 16 hrs. TLC test
(Ethyl acetate/Hexane=5:2, v/v) proved that none of the starting material was left. After the
solvent was removed at reduced pressure, the residue was purified by flash matography (Ethyl
acetate/Hexane=5:2, v/v, Rf=0.3). Compound 7 was obtained as a white foam, 4.1g, yield
96.8%. HRMS (m/z) calcd. for C46H65NO8 (M+H)+: Cal. 760.4783, Found 760.4795,
5
1
HNMR(CDCl3, 600 MHz,) δ: 0.68 (s, 3 H,), 0.88 (s, 3 H,), 0.96 (d, J= 6.6 Hz, 3 H,), 1.12~2.30
(m, 23 H,), 1.43 (s, 9H, tertiary butyl), 3.12 (m, 1 H,), 3.20 (m, 1 H,), 3.39 (m, 2 H,), 3.51 (m, 1
H,), ), 3.83 (s, 2 H,), 3.96 (s, 1 H), 4.12 (m, 1 H,), 4.20 (t, J=7.2 Hz, 1 H,), 4.39 (d, J= 7.2 Hz, 2
H,), 5.41 (m, 1 H,), 7.30~7.76 (m, 8 H, Fmoc).
Preparation of (3α, 5β, 7α, 12α)-7, 12-Dihydroxy-3-(3-Fmocamino-2-hydroxy-1-propoxy)-cholic
acid 8
TFA (100 mL) was dropped into the solution of compound 7 (11.0 g, 14.48mmol) in CH2Cl2
(100 mL) under stirring below 0°C. The mixture was then stirred at room temperature for
another 4.5 hrs. After the solvents were moved by air blowing, the residue was dissolved into
CH2Cl2 (300 mL) and was washed with 3×100 mL water. After drying with anhydrous Na2SO4
overnight, the organic layer was evaporated under reduced pressure. A pink yellow jelly was
obtained and purified by flash chromatography (Ethyl acetate/CH3OH=20:1, v/v, Rf=0.3).
Compound 8 was obtained as a white foam, 9.0 g, yield 88.40%, HRMS (m/z) calcd. for
C42H57NO8 (M+H)+: Cal. 704.4157, Found 704.4162, 1HNMR (CDCl3, 600 MHz,): δ:0.66 (s, 3
H,), 0.87 (s, 3 H,), 0.98 (d, J= 6.6 Hz, 3 H,), 1.08 (m, 1 H,), 1.15~2.37 (m, 23 H,), 3.10 (m, 1 H,),
3.11 (s, 1 H,), 3.39 (m, 2 H,), 3.49 (m, 1 H,), 3.61 (s, 1 H,), 3.82 (s, 1 H,), 3.85 (s, 1H,), 3.95 (s, 1
H,), 4.11 (m, 2 H,), 4.20 (t, J=7.2 Hz, 1 H,), 4.38 (d, J= 7.2 Hz, 2 H,), 5.60 (s, 1 H,), 7.28~7.75
(m, 8 H,Fmoc). ;
Preparation of HOSu esters 9, 10 and 11
Compound 7, 5 or 8 was dissolved into CH2Cl2 containing SuOH (1.2 eq.) and DCC (1.2 eq.),
and the mixture was stirred at room temperature for 16 hrs. The white precipitate (DCU) was
filtered off and the filtrate was condensed under reduced pressure until a white foam appeared.
After the foam dissolved in ethyl acetate, the solution stood overnight at 4°C for the precipitation
of DCU. After the DCU was filtered off, the filtrate was condensed again. The obtained product
was used directly for coupling without further purification.
Preparation of cholic acid dimers with different glycerol derivatives
0.33 mmol of lysine mono-HCl salt was dissolved in a 3 mL of mixed solvent of acetone and
H2O (v:v=1:1). 1 mL of Et3N (2.63mmol) in acetone was added slowly. The solution was stirred
6
for 5 min, 0.825 mmol of NHS ester of 9, 10 and 11 were dissolved in 1 mL acetone and then
add dropwise into an individual above solution, respectively. The solutions were stirred for 2
days at room temperature. Kaiser test was performed to check the completion of the reaction.
The solutions were adjusted to pH 2 by adding a 10% HCl solution. Then acetone was
evaporated out and white precipitate was collected and dried under vacuum. The crude products
were separated via column chromatograph (EtoAc : MeOH=3:1) and white products were
obtained. The products were characterized via proton NMR and MALDI-TOF mass
spectrometer. Compound KCA2 was obtained as a white foam. MALDI-TOF MS (m/z) calcd. for
C54H90N2O10Na (M+Na)+: Cal.: 949.649, Found 949.501,
1
HNMR(DMSO-d6, 600 MHz,) δ:
0.54 (d, J= 2.8 Hz, 6 H,), 0.77 (s, 6 H,), 0.89 (d, J= 5.9 Hz, 6 H,), 1.12~2.30 (m, 46 H), 2.93 (m,
1H), 3.13 (m, 2 H), 3.56 (s, 2H), 3.75 (s, 2 H), 3.94 (s, 1 H), 4.2 (s, 2 H), 4.04 (s, 2 H), 3.27 (s, 2
H), 7.60 (s, 1 H, NH), 7.67 (t, J= 5.5 Hz, 1 H, NH), 12.3 (s, 1 H, COOH); Compound K(CA4OH)2 was obtained as a white foam. MALDI-TOF MS (m/z) calcd. for C60H102N2O14Na
(M+Na)+: Cal.: 1097.723, Found 1097.545,
1
HNMR(CDCl3, 600 MHz,) δ: 0.55 (s, 6 H,), 0.78
(s, 6 H,), 0.92 (t, J= 7.0 Hz, 6 H,), 1.12~2.30 (m, 46 H,), 2.93 (m, 1 H), 2.99 (m, 2H), 3.25 (m,
4H), 3.32 (m, 4 H), 3.46(m, 2H), 3.58 (s, 2 H), 3.75 (s, 2 H), 3.90 (s, 1 H), 3.96 (s, 2 H), 7.447.74 (q, 2 H, NH), 12.12 (s, 1 H, COOH); Compound K(CA-5OH)2 was obtained as a white
foam. MALDI-TOF MS (m/z) calcd. for C66H114N2O18Na (M+Na)+: Cal.: 1245.796, Found
1245.397,
1
HNMR(CDCl3, 600 MHz,) δ: 0.56 (d, J= 19.5 Hz, 6 H,), 0.80 (s, 6 H,), 0.89 (t, J=
8.5 Hz, 6 H,), 1.12~2.30 (m, 46 H,), 2.89-3.10 (m, 5 H,), 3.15-3.56 (m, 20H), 3.58 (m, 2H), 3.74
(s, 2 H), 4.07 (m, 1 H), 7.69 (t, 1 H, J= 4.2 Hz, NH), 7.93 (d, 1 H, J= 6.6 Hz, NH), 12.35 (s, 1
H, COOH).
7
Compound 2
Ha
Hb
Compound 3
Ha+Ha’
Hb+Hb’
8
Compound 4
a
b+d
c
Compound 5
5 OH
9
Compound 6
d,e
c
NH2
a,b
t-Bu
Compound 7
18-Me
Fmoc
10
18-Me
Fmoc
Compound 8
EtOAc
Figure S-1 1H NMR spectrum of intermediate of cholic acid derivatives
11
2596 #65-74 RT: 1.06-1.21 AV: 10 NL: 1.03E6
T: FTMS + p ESI Full ms [150.00-2000.00]
1058.7894
100
95
Compound 2
[2M+NH4]+
90
Calculated [M+H]+ = 521.3837
85
80
75
[2M+Na]+
70
Relative Abundance
65
[M+NH4]+
60
538.4104
55
[2M+H]+
50
1041.7639
45
40
35
30
355.2635
[M+H]+
25
20
429.3002
15
579.4368
10
5
465.3211
202.5883
1121.7019
729.4555
0
200
300
400
500
600
700
m/z
800
900
1000
1100
1200
12
2596 #246-254 RT: 4.08-4.21 AV: 9 NL: 2.81E6
T: FTMS + p ESI Full ms [150.00-2000.00]
594.4375
100
95
Compound 3
[M+NH4]+
Calculated [M+NH4]+ = 594.4364
90
85
80
75
70
Relative Abundance
65
60
55
[M+Na]+
50
45
40
35
30
25
[M+K]+
20
[2M+NH4]+
615.3654
15
1170.8417
355.2635
429.3003
10
[2M+Na]+
1019.7174
635.4630
5
0
200
300
400
500
600
700
800
m/z
900
1000
1100
1200
1300
1400
13
2596 #431-436 RT: 7.16-7.25 AV: 6 NL: 4.27E5
T: FTMS + p ESI Full ms [150.00-2000.00]
242.2839
100
[2M+Na]+
987.6394
95
90
85
Compound 4
80
Calculated [M+H]+ = 483.3317
75
70
355.2633
Relative Abundance
65
[M+H]+
60
483.3315
55
50
[M+Na]+
45
40
505.3130
35
30
447.3105
25
20
15
373.2738
[2M+H]+
202.5871
965.6574
1009.6204
10
599.3915
5
0
200
300
400
500
600
700
800
m/z
900
1000
1100
1200
1300
14
2596 #1303-1308 RT: 21.70-21.78 AV: 6 NL: 2.78E5
T: FTMS + p ESI Full ms [150.00-2000.00]
538.4097
100
95
90
Compound 5
[M+H]+
85
Calculated [M+H]+ = 557.3684
80
75
70
Relative Abundance
65
[M+Na]+
60
579.3498
55
50
45
741.4394
40
35
30
25
202.6024
1097.7967
20
355.2633
871.5033
15
447.3104
709.4131
696.3670
10
1135.7123 1233.7707
5
0
200
300
400
500
600
700
800
m/z
900
1000
1100
1200
1300
15
2596 #1088-1097 RT: 18.11-18.26 AV: 10 NL: 4.81E5
T: FTMS + p ESI Full ms [150.00-2000.00]
760.4795
100
[2M+Na]+
1542.9349
95
[M+H]+
90
[2M+H]+
1520.9562
85
Compound 7
80
Calculated [M+H]+ = 760.4783
75
70
[M+Na]+
Relative Abundance
65
782.4605
60
55
50
704.4164
45
40
35
30
25
20
929.5029
15
686.4057
202.6025
818.5317
10
5
0
200
300
400
500
600
700
800
900
m/z
1000
1100
1200
1300
1400
1500
16
2596 #707-713 RT: 11.77-11.86 AV: 7 NL: 2.30E5
T: FTMS + p ESI Full ms [150.00-2000.00]
704.4162
100
95
[M+H]+
90
Compound 8
85
Calculated [M+H]+ = 704.4157
80
75
[M+Na]+
70
726.3975
Relative Abundance
65
60
[2M+Na]+
55
1429.8074
50
45
[2M+H]+
40
1408.8293
35
30
202.5997
25
686.4054
20
800.3986
668.3947
822.3805
540.1756
15
10
369.3839
314.1388
5
1525.7884
457.2769
1203.1775
0
200
300
400
500
600
700
800
900
m/z
1000
1100
1200
1300
1400
1500
1600
Figure S-2 HR MS of intermediate of cholic acid derivatives
17
K(CA)2
K(CA-4OH)2
K(CA-5OH_7)2
K(CA-5OH_12)2
K(CA-5OH_7_12)2
K(CA-4OH-NH2)2
K(CA-4OH-NH3+)2
Figure S-3. Representative potential energy profiles for each of the CA structures showing
E  E Folded  EOpen as a function of time. In the simulated annealing process, the temperature
was gradually dropped from 1000 to 5 K over 1 ns after initial equilibration at 1000 K for 200 ps.
K(CA-5OH_12)2
K(CA-5OH-7/12)2
Charged K(CA-3OH-NH3+)2
Figure S-4 The energy-minimized folded conformations of the CA dimers (in vacuum) with
varying glycerol substitutions.
18
Split of 18-Me
N-H
C-H in glycerol
K(CA-5OH)2
K(CA-4OH)2
K(CA)2
Figure S-5 Proton NMR spectra of the CA dimers with different glycerol substitutions.
19
Intens. [a.u.]
949.501
[M(OH) + Na]+
5000
4000
3000
[M(ONa)+ Na]+
971.491
2000
1000
0
Intens. [a.u.]
800
x104
900
[M(OH) + Na]+
1.0
1000
1100
1200
1300
m/z
1097.545
[M(ONa)+ Na]+
1119.532
0.8
0.6
0.4
0.2
0.0
950
1000
1050
1100
1150
1200
1250
1300
1350
1400
m/z
20
Intens. [a.u.]
x104
8
1245.397
[M(OH) + Na]+
[M(OH)+ K]+
6
1261.357
4
2
1283.339
0
1230
1240
1250
1260
1270
1280
1290
1300
1310
1320
m/z
Figure S-6 MALDI-TOF MS spectra of the CA dimers with different glycerol substitutions.
CMC studies via Pyrene as a probe
5k
PEG CA8 (I)
0.8
5k
PEG (CA-4OH)8 (II)
5k
PEG (CA-5OH)8 (III)
I3/I1
5k
PEG (CA-NH2)8 (IV)
0.6
0.4
0.1
1
10
100
Concentration g/mL)
Figure S-7 CMC studies of telodendrimers using fluorescent pyrene as a probe molecule.
21
Figure S-8 The particle sizes of telodendrimer III PEG5k(CA-5OH)8 before (1 nm & 5nm) and
after being loaded with PTX (62 nm & 295 nm).
22
Figure S-9 The particle sizes of telodendrimer IV PEG5k(CA-3OH-NH2)8 before (340 nm) and
after being loaded with PTX (51 nm & 341 nm).
23
100
DID Release from NP-I & NP-II
% DiD Release
80
DID-NP-I
60
DID-NP-II
40
20
0
0
8
16
24
32
40
48
Time (hr)
Figure S-10 The release profile DiD from telodendrimer I PEG5kCA8 and telodendrimer
PEG5k(CA-4OH)8 by dialysis method (MWCO 3,500 Da) under sink conditions with frequent
refresh of the medium in the reservoir.
1.
2.
3.
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