Imaging and Tumour Therapy Combined with NIR Irradiation ... · Upconversion Nanotheranostic Agent...
Transcript of Imaging and Tumour Therapy Combined with NIR Irradiation ... · Upconversion Nanotheranostic Agent...
Upconversion Nanotheranostic Agent Activated by Hypoxia
Combined with NIR Irradiation for Selective Hypoxia
Imaging and Tumour Therapy
Hongliang Li,† Weiyan Lei,† Jianong Wu, Shenghui Li, Guoqiang Zhou,* Dandan Liu, Xinjian Yang, Shuxiang Wang,* Zhenhua Li, and Jinchao Zhang*College of Chemistry & Environmental Science, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Chemical Biology Key Laboratory of Hebei Province, Hebei University, Baoding, 071002, China
[email protected], (tel)++86 312 507 9359, (fax) ++86 312 507 9359; [email protected]; (tel) ++86 312 507 9359, (fax) ++86 312 507 9359; [email protected], (tel) ++86 312 507 9525; (fax) ++86 312 507 9525
Supplementary Information
Electronic Supplementary Material (ESI) for Journal of Materials Chemistry B.This journal is © The Royal Society of Chemistry 2018
1. The characterization of FDU-CAE-NO2 and UCNP-CAE-FDU/NO2
2-(4-Nitrobenzyloxy)-4-(prop-2-ynyloxy)benzaldehyde (2) : A yellow solid, Mp:
CHO
O
ONO2
163.3-164.8 oC; 1H-NMR (600 MHz, DMSO-d6): δ 10.31 (s, 1 H), 8.28 (d, 2 H, J = 8.4 Hz, ), 7.80 (d, 2 H, J =
8.4 Hz), 7.73 (d, 1 H, J = 8.4 Hz), 6.86 (d, 1 H, J = 2.4 Hz), 6.76 (d, 1 H, J = 8.4 Hz), 5.46 (s, 2 H), 4.94 (d, 2 H, J
= 2.4 Hz), 3.64 (s, 1 H). 13C NMR (DMSO-d6, 150 MHz, ppm): δ 187.42, 163.66, 161.66, 147.10, 144.15,
130.18, 128.19, 123.68, 118.99, 107.70, 100.66, 78.90, 78.38, 68.67, 56.04. HRMS (ESI) m/z calcd for
C17H13NO5 [M+H]+ 312.08665, found 312.08673.
(E)-tert-Butyl-3-(2-(4-nitrobenzyloxy)-4-(prop-2-ynyloxy)phenyl) acrylate (4) : A
OO
NO2
O
O
white solid. Mp: 145.7-148.3 oC; 1H-NMR (DMSO-d6, 600 MHz, ppm): δ 8.29 (d, 2H, J = 9.0 Hz), 7.83 (d, 1 H,
J = 15.6 Hz), 7.74 (d, 2 H, J = 9.0 Hz), 7.72 (d, 1H, J = 9.0 Hz), 6.76 (d, 1H, J = 2.4 Hz), 6.67 (dd, 1H, J = 9.0,
2.4 Hz,) 6.42 (d, 1H, J = 15.6 Hz) , 5.39 (s, 2H), 4.86 (d, 2H, J = 2.4 Hz), 3.60 (s, 1H) , 1.47 (s, 9H). 13C NMR
(DMSO-d6, 150 MHz, ppm): δ 166.00, 160.20, 157.53, 147.11, 144.40, 137.70, 129.67, 128.22, 123.67,
117.71, 116.37, 107.27, 100.73, 79.46, 78.74, 78.51, 68.64, 55.73, 27.81. HRMS (ESI) m/z calcd for
C23H23NO6 [M+H]+ 410.15981, found 410.16003.
(E)-3-(2-(4-Nitrobenzyloxy)-4-(prop-2-ynyloxy)phenyl)acrylic acid (5) : A white solid,
OO
OH
O
NO2
Mp: 197.6-199.5 oC. 1H-NMR (DMSO-d6, 600 MHz, ppm): δ 8.28 (d, 2 H, J = 8.4 Hz), 7.73 (d, 2 H, J = 8.4 Hz),
7.50 (d, 1 H, J = 8.4 Hz), 7.47 (d, 1 H, J = 15.6 Hz), 6.69 (d, 1 H, J = 2.4 Hz), 6.60 (dd, 1 H, J = 9.0, 2.4 Hz),
6.30 (d, 1 H, J = 15.6 Hz) , 5.34 (s, 2 H), 4.79 (d, 2 H, J = 2.4 Hz), 3.56 (s, 1 H). 13C NMR (DMSO-d6, 150 MHz,
ppm): δ 167.99, 160.14, 157.54, 147.18, 144.35, 138.22, 128.39, 123.73, 117.22, 116.48, 107.29, 100.76,
78.76, 78.51, 68.64, 55.74. HRMS (ESI) m/z calcd for C19H15NO6 [M+H]+ 354.09721, found 354.09723.
FDU-CAE-NO2 : A white solid. Mp: 143.4-146.3 oC. 1H NMR (DMSO-d6, 600
OO
O
O
NO2
NHN
OO
HO
O
F
MHz, ppm): δ 11.88 (s, 1 H), 8.28 (d, 2 H, J = 8.7 Hz), 7.92 (d, 1 H, J = 16.0 Hz), 7.87 (d, 1 H, J = 6.8 Hz), 7.75
(d, 1 H, J = 8.8 Hz), 7.72 (d, 2 H, J = 8.7 Hz), 6.77 (d, 1 H, J = 2.0 Hz), 6.69 (dd, 1 H, J = 8.8, 2.0 Hz), 6.60 (d, 1
H, J = 16.0 Hz), 6.14 (t, 1 H, J = 6.4 Hz), 5.51 (d, 1 H, J = 4.4 Hz), 5.40 (d, 2 H, J = 3.2 Hz), 4.87 (d, 2 H, J = 2.0
Hz), 4.40-4.28 (m, 3 H), 4.01 (s, 1 H), 3.61 (s, 1 H), 2.24-2.09 (m, 2 H). 13C NMR (DMSO-d6, 150 MHz, ppm):
δ 166.47, 160.54, 157.03, 157.03, 156.77, 148.86, 147.09, 144.29, 141.12, 139.43, 138.83, 130.21, 128.26,
124.53, 124.19, 123.71, 116.12, 115.53, 107.34, 100.73, 84.55, 83.97, 78.71, 78.59, 70.00, 68.65, 63.67,
55.77. HRMS (ESI) m/z calcd for C28H24N3FO10 [M+H]+ 582.15185, found 582.15216.
7-Propargyloxycoumarin (CM) : A white solid yield, Mp: 70.3-71.8 oC. 1H NMR (CDCl3, O OO
600 MHz, ppm): δ 7.64 (d, 1 H, J = 9.6 Hz), 7.41 (d, 1 H, J = 8.4 Hz), 6.94 (s, 1 H), 6.92 (d, 1 H, J = 8.4 Hz),
6.29 (d, 1 H, J = 9.6 Hz), 4.77 (d, 2 H, J = 2.4 Hz), 2.56 (s, 1 H). 13C NMR (CDCl3, 150 MHz, ppm): δ 160.98,
160.55, 155.66, 143.27, 128.84, 113.67, 113.20, 113.05, 102.16, 77.38, 76.57, 56.22. HRMS (ESI) m/z calcd
for C12H8O3 [M+H]+ 201.05462, found 201.05461.
2. The size of UCNP-CAE-FDU/NO2 and UCNP analyzed by DLS and TEM
The samples for TEM and DLS were prepared by dispersing UCNP-CAE-FDU/NO2 (200 μg/mL) in PBS
(25 mmol/L, pH 7.4) with intermittent ultrasonic by a needle type ultrasonic instrument. The samples of
UCNP were dispersed in cyclohexane (20 μg/mL). The TEM sample was prepared by dropping on the
surface of a copper grid and negative staining for 30 s by a droplet of phosphotungstic acid. The DLS of the
samples were measured using a Nano-ZS system in disposable cuvettes.
3. HPLC and HRMS analysis
Figure S1. HPLC profiles of a) FDU; b) FDU-CAE-NO2; c) CM; d) solution of FDU-CAE-NO2 incubated with
Na2S2O4 and then illuminated by UV light at 365 nm; e) UCNP-CAE-FDU/NO2 incubated with Na2S2O4 and
then illuminated by NIR light at 980 nm
Figure S2. HRMS of the solution of FDU-CAE-NO2 incubated with Na2S2O4 and then illuminated by UV-light at 365 nm
[M+H]+(C12H9O3): 201.05462
O OO
[M+H]+(C9H12FN2O5): 247.07248
NH
N
OO
HO
HO O
F
OOO
O
NO2
NHN
OO
HO
O
F
[M+H]+(C28H25FN3O10): 582.15185
Figure S3. HRMS of the mixture of UCNP-CAE-FDU/NO2 with Na2S2O4 and then illuminated by NIR-light at 980 nm
4. NMR, IR and HRMS spectra
CHO
OO
NO2
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.5f1 (ppm)
0.88
2.08
2.21
1.05
1.00
1.09
2.11
2.22
1.00
3.64
4.93
4.94
5.45
6.75
6.76
6.86
6.86
7.72
7.74
7.81
8.27
8.28
10.3
1
Figure S4. 1H NMR of 2-(4-nitrobenzyloxy)-4-(prop-2-ynyloxy)benzaldehyde (2)
[M+H]+(C9H12FN2O5): 247.07248
NH
N
OO
HO
HO O
F
0102030405060708090100110120130140150160170180190f1 (ppm)
56.0
41
68.6
65
78.3
7878
.904
100.
655
107.
697
118.
991
123.
679
128.
186
130.
183
144.
148
147.
100
161.
655
163.
664
187.
420
CHO
OO
NO2
Figure S5. 13C NMR of 2-(4-nitrobenzyloxy)-4-(prop-2-ynyloxy)benzaldehyde (2)
CHO
OO
NO2
Figure S6. HRMS of 2-(4-nitrobenzyloxy)-4-(prop-2-ynyloxy)benzaldehyde (2)
Figure S7. IR of 4-nitrobenzyloxy-4-diethylaminobenzaldehyde (2)
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)
9.41
0.92
2.08
2.02
1.00
1.22
1.01
1.13
2.02
1.01
2.13
1.47
1
3.59
5
4.85
74.
860
5.39
3
6.40
76.
434
6.66
16.
665
6.67
6
6.75
87.
708
7.72
27.
730
7.74
57.
814
8.28
18.
296
OO
NO2
OO
Figure S8. 1H NMR of (E)-tert-butyl-3-(2-(4-nitrobenzyloxy)-4-(prop-2-ynyloxy)phenyl)acrylate (4)
0102030405060708090100110120130140150160170f1 (ppm)
27.8
10
55.7
25
68.6
43
78.5
0578
.741
79.4
56
100.
734
107.
271
116.
369
117.
714
123.
658
128.
215
129.
661
137.
695
144.
397
147.
114
157.
525
160.
195
166.
001
OO
NO2
OO
Figure S9. 13C NMR of (E)-tert-butyl-3-(2-(4-nitrobenzyloxy)-4-(prop-2-ynyloxy)phenyl)acrylate (4)
OO
NO2
OO
Figure S10. HRMS of (E)-tert-butyl-3-(2-(4-nitrobenzyloxy)-4-(prop-2-ynyloxy)phenyl)acrylate (4)
Figure S11. IR of (E)-tert-butyl-3-(2-(4-nitrobenzyloxy)-4-(prop-2-ynyloxy)phenyl)acrylate (4)
OOOH
O
NO2
2.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)
1.04
2.00
2.00
1.00
1.00
0.98
0.94
1.03
2.01
2.01
3.55
6
4.78
74.
791
5.34
2
6.29
16.
317
6.59
26.
595
6.60
6
6.68
47.
453
7.47
97.
493
7.72
27.
736
8.26
78.
281
Figure S12. 1H NMR of (E)-3-(2-(4-nitrobenzyloxy)-4-(prop-2-ynyloxy)phenyl)acrylic acid (5)
0102030405060708090100110120130140150160170180f1 (ppm)
55.7
36
68.6
38
78.5
1378
.756
100.
758
107.
293
116.
481
117.
222
123.
729
128.
390
138.
222
144.
351
147.
177
157.
536
160.
143
167.
990
OOOH
O
NO2
Figure S13. 13C NMR of (E)-3-(2-(4-nitrobenzyloxy)-4-(prop-2-ynyloxy)phenyl)acrylic acid (5)
OO
NO2
OHO
Figure S14. HRMS of (E)-3-(2-(4-nitrobenzyloxy)-4-(prop-2-ynyloxy)phenyl)acrylic acid (5)
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.511.5f1 (ppm)
2.06
1.03
1.00
3.09
2.00
2.01
1.00
1.04
1.07
0.97
1.01
3.00
1.01
1.03
2.07
1.01
2.09
42.
244
3.60
7
4.01
04.
282
4.87
0
5.50
65.
517
6.12
9
6.57
76.
617
6.77
07.
707
8.26
68.
287
11.8
65
OOO
O
NO2
NHNO
O
HO
O
F
Figure S15. 1H NMR of FDU-CAE-NO2
OOO
O
NO2
NHN
OO
HO
O
F
0102030405060708090100110120130140150160f1 (ppm)
55.7
68
63.6
73
68.6
5470
.004
78.5
90
83.9
7184
.545
100.
730
107.
341
115.
332
116.
118
123.
707
128.
257
130.
208
138.
825
139.
436
141.
123
144.
294
156.
774
157.
034
160.
544
166.
465
Figure S16. 13C NMR of FDU-CAE-NO2
OOO
O
NO2
NHNO
O
HOOF
Figure S17. HRMS of FDU-CAE-NO2
Figure S18. IR of FDU-CAE-NO2
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
1.00
2.23
1.07
1.03
1.01
1.08
1.08
2.58
5
4.76
64.
770
6.27
86.
294
6.91
26.
926
6.94
3
7.40
1
7.64
77.
663
O OO
Figure S19. 1H NMR of CM
0102030405060708090100110120130140150160f1 (ppm)
56.2
20
76.5
6777
.379
102.
159
113.
049
113.
201
113.
671
128.
841
143.
268
155.
655
160.
552
160.
981
O OO
Figure S20. 13C NMR of CM
O OO
Figure S21. HRMS of CM
Figure S22. IR of CM
Figure S23. IR of UCNPs
Figure S24. IR of UCNP-CAE-FDU/NO2