Supporting Information Red-light-responsive supramolecular valves ...
Supporting Information Red-light-responsive supramolecular valves for photo-controlled drug release from mesoporous nanoparticles Dongsheng Wang and Si Wu* Max Planck Institute for Polymer Research, Ackermannweg 10, 55128, Mainz, Germany Email: [email protected]
1. Materials 2,6-Dimethoxyaniline (C8H11NO2, CAS No. 2734-70-5) and β-cyclodextrin (β-CD) (C42H70O35,
CAS
No.
7585-39-9)
were
purchased
from
Alfa
Aesar.
3,5-Dimethoxyaniline (C8H11NO2, CAS No. 10272-07-8), sodium nitrite (NaNO2, CAS No. 7632-00-0), hexadecyltrimethylammonium bromide (CTAB) (C19H42BrN, CAS No. 57-09-0), tetraethyl orthosilicate (TEOS) (C8H20O4Si, CAS No. 78-10-4) and
(3-isocyanatopropyl)triethoxysilane
(3-ICPES)
(C10H21NO4Si,
CAS
No.
24801-88-5) were purchased from Sigma Aldrich. Doxorubicin hydrochloride (DOX) (C27H30NO11Cl, CAS No. 25316-40-9) was used as the model drug and purchased from Sigma Aldrich. All the solvents (HPLC grade) were purchased from Sigma Aldrich and were directly used without any further purification. Milli-Q water (resistivity: 18.2 MΩ×cm) provided by a Sartorius Arium 611 VF Purification System was used throughout the project.
2. Methods 1
H and
13
C nuclear magnetic resonance (NMR) spectra were recorded on a Bruker
Avance 250 MHz spectrometer. The 1H-NMR experiments were acquired with a 5 mm BBI z-gradient probe on the 700 MHz Bruker AVANCE III system. For a proton spectrum, 128 transients were used with a 10 µs long 90° pulse and a 12600 Hz spectral width together with a recycling delay of 5 s. The
13
C NMR (176 MHz)
measurements were made with a J-modulated (coupling constant of 145Hz 1H-13C was used) spin-echo for C-nuclei coupled to protons to determine the number of attached protons and proton decoupling during acquisition. The 90° pulse for carbon was 14.5 s long and 16000 scans were taken with a relaxation delay of 2 s. The temperature was regulated at 298.3 K and calibrated with a standard 1H methanol NMR sample using the topspin 3.2 software (Bruker). The control of the temperature was realized with a VTU (variable temperature unit) and an accuracy of +/- 0.1 K. Before Fourier transformation, the data were zero filled to 1024 points in f1 and multiplied by a window function (q-sine bell or sine bell) in both dimension. The spectral widths were 30000 Hz (236 ppm) for 13C and 9000 Hz (18 ppm) for 1H, both nuclei with a relaxation delay of 2.5 s. Proton and carbon spectra were referenced using the solvents signals (DMSO-d5H=2.49 ppm and
13
C: DMSO-d6=39.5 ppm) as
an internal standard. Mass spectra (MS) were obtained using a VG instrument ZAB 2-SE-FPD. UV/Vis absorption spectra were measured on a Lambda 900 spectrometer (Perkin Elmer).
Transmission electron microscopy (TEM) images were measured on a JEOL JEM1400 system. To prepare the TEM samples, a drop of the particle suspension in water was placed onto a 200-mesh copper TEM grid and dried at room temperature. Nitrogen adsorption-desorption isotherms were measured at 77 K on a Micromeritics Tristar II surface area and pore size analyzer. X-ray diffraction (XRD) patterns were recorded on a Fine focus anode system with Cu Kα line (λ=0.15418 nm). Photoisomerization was induced by the LEDs with the wavelengths of 470 and 625 nm (device types LCS-0470-03-22 and LCS-0625-03-22, Mightex Systems). The output intensities of the LEDs were controlled by an LED controller (device type SLC-MA04-MU, Mightex Systems) and were calibrated by an optical powermeter (Model 407A, Spectra-Physics Corporation).
3. Synthesis
Figure S1. Route for the synthesis of 5 (mAzo-Si).
Synthesis of 3 (mAzo-NH2) The synthesis of mAzo-NH2 was as our previous work.1 1
HNMR (DMSO-d6, 250 MHz): δ=7.15 (t, J=8.3 Hz, 1H; Ar-H), δ=6.71 (d, J=8.4 Hz,
2H; Ar-H), δ=5.99 (s, 2H; Ar-NH2), δ=5.94 (s, 2H; Ar-H), δ=3.67 (d, J=1.7 Hz, 12H; -OCH3); 13CNMR (DMSO-d6, 250 MHz): δ=156.1 (Ar-C), δ=153.4 (Ar-C), δ=151.0 (Ar-C), δ=126.6 (Ar-C), δ=123.4 (Ar-C), δ=105.3 (Ar-C), δ=89.9 (Ar-C), δ=55.9 (-OMe), δ=55.4 (-OMe); MS m/z=316.3.
Synthesis of 5 (mAzo-Si) The synthesized 3 (0.032 g, 0.10 mmol) was mixed with 3-ICPES (4 in Figure S1) (0.018 g, 0.11 mmol) in 6 mL of THF. The mixture was heated under reflux and an atmosphere of N2 overnight. After removal of the solvent,
the residue was recrystallized in hexane/THF to get the mAzo-Si. Yield: 78%. 1
HNMR (DMSO-d6, 250 MHz): δ=8.86 (s, 1H; Ar-NH-CO), δ=7.27 (t, J=8.4 Hz, 1H;
Ar-H), δ=6.96 (s, 2H; Ar-H), δ=6.80 (d, J=8.4 Hz, 2H; Ar-H), δ=6.36 (t, J=5.7 Hz, 1H; C-NH-CO), δ=3.83 (t, J=8.4 Hz, 6H; -OCH2-), δ=3.72 (s, 12H; -OCH3), δ=3.14 (q, J=6.6 Hz, 2H; N-CH2-), δ=1.63-1.48 (m, 2H; -CH2-), δ=1.21 (t, J=7.0 Hz, 9H; -CH3), δ=0.70-0.55 (m, 2H; -CH2-Si).
13
CNMR (DMSO-d6, 250 MHz): δ=154.8 (C=O),
δ=153.6 (Ar-C), δ=151.0 (Ar-C), δ=143.5 (Ar-C), δ=134.5 (Ar-C), δ=128.0 (Ar-C), δ=127.1 (Ar-C), δ=105.3 (Ar-C), δ=93.9 (Ar-C), δ=57.7 (-O-CH2), δ=56.0 (-OCH3), δ=55.7 (-OCH3), δ=41.7 (-N-CH2-), δ=23.3 (-CH2-), δ=18.2 (-CH3), δ=7.2 (-CH2-Si).
4. Photoisomerization of mAzo-Si
Figure S2. UV/vis spectra (a) of the mAzo-Si (1.3 mg in 15 mL DMSO) after treating with a sequence of red/blue light (60 mW/cm2, 30 min) and heating (60 oC, 600 min), the absorbance at 340 nm is also showed (b).
5. Synthesis of mesoporous silica nanoparticles (MSNs) The MSNs were synthesized as the reported procedures.1 In a typical synthesis, CTAB (1.000 g, 3.00 mmol) was added to 480 mL of H2O. Then 3.5 mL of NaOH (2 M) aqueous solution was added and induced the complete dissolving of the CTAB. The solution was then heated to 80 °C under stirring. TEOS (5.000 mL, 23.0 mmol) was added to the solution slowly over several minutes, during the adding the precipitate could be observed. The reaction was kept at 80 °C for 2 h under vigorous stirring. Then the solution was filtered while hot using a fritted funnel, the white solid was washed with H2O and MeOH for several times. Then the solid was dried in an oven at 100 °C for over 24h to get the MSNs.
6. Photoresponse of MSNs-Azo
Figure S3. UV/vis spectra of MSNs (5 mg in 1 mL PBS pH=7.4) and MSNs-Azo (5 mg in 1 mL PBS pH=7.4) before and after red and blue light irradiating (60 mW/cm2, 30 min).
7. DOX loading capacity of MSNs-Azo/DOX/CD The loading capacity of the DOX in the nanoparticles was calculated as our previous work.2 After the loading of DOX, the nanoparticles were collected by centrifugation, and the DOX concentration of the residual solution was measured via the UV/vis spectrophotometer. The nanoparticles were washed for three times to remove the adsorbed DOX on surface, and the DOX concentrations in the eluted solutions were measured. The loading capacity of the DOX in the nanoparticles could be calculated by the followed equation:
where LCDOX is the DOX loading capacity (wt. %); m is the weight of the nanoparticles (mg); Cloading, Cresidual, C1, C2 and C3 are the concentrations of the DOX in the original loading solution, residual solution and the eluted solutions for the 1st, 2nd and 3rd time, respectively (mg/mL); Vloading, Vresidual, V1, V2 and V3 are the volumes of the original loading solution, residual solution and the eluted solutions for the 1st, 2nd and 3rd time, respectively (mL).
Figure S4. UV/vis spectra of the eluted solutions for MSNs-Azo/DOX/CD. The DOX loading capacity of the MSNs-Azo/DOX/CD was calculated to be 3.21 wt.%.
8. Red light induced DOX release
Figure S5. UV/vis spectra of the MSNs-Azo/DOX/CD in the dark (a), under 15 mW/cm2 red light (b) and 60 mW/cm2 red light (c) irradiation for different time. UV/vis spectra of the MSNs-Azo/DOX/CD under 15 mW/cm2 red light (d) and 60 mW/cm2 red light (e) irradiation for different time when a piece of tissue was placed between the sample and LED. The amount of released DOX is shown in Fig. 3(b) in the main manuscript.
9. NMR spectra of new compounds
Figure S6. 1HNMR spectrum of the mAzo-Si.
Figure S7. 13CNMR spectrum of the mAzo-Si
Reference 1. Ferris, D.P.; Zhao, Y.-L.; Khashab, N. M.; Khatib, H. A.; Stoddart, J. F.; Zink, J. I. Light-Operated Mechanized Nanoparticles. J. Am. Chem. Soc. 2009, 131, 1686-1688. 2. He, S.; Krippes, K.; Ritz, S.; Chen, Z.; Best, A.; Butt, H.-J.; Mailänder, V.; Wu, S. Ultralow-intensity near-infrared light induces drug delivery by upconverting nanoparticles. Chem. Commun. 2015, 51, 431-434.
1. Materials 2,6-Dimethoxyaniline (C8H11NO2, CAS No. 2734-70-5) and β-cyclodextrin (β-CD) (C42H70O35,
CAS
No.
7585-39-9)
were
purchased
from
Alfa
Aesar.
3,5-Dimethoxyaniline (C8H11NO2, CAS No. 10272-07-8), sodium nitrite (NaNO2, CAS No. 7632-00-0), hexadecyltrimethylammonium bromide (CTAB) (C19H42BrN, CAS No. 57-09-0), tetraethyl orthosilicate (TEOS) (C8H20O4Si, CAS No. 78-10-4) and
(3-isocyanatopropyl)triethoxysilane
(3-ICPES)
(C10H21NO4Si,
CAS
No.
24801-88-5) were purchased from Sigma Aldrich. Doxorubicin hydrochloride (DOX) (C27H30NO11Cl, CAS No. 25316-40-9) was used as the model drug and purchased from Sigma Aldrich. All the solvents (HPLC grade) were purchased from Sigma Aldrich and were directly used without any further purification. Milli-Q water (resistivity: 18.2 MΩ×cm) provided by a Sartorius Arium 611 VF Purification System was used throughout the project.
2. Methods 1
H and
13
C nuclear magnetic resonance (NMR) spectra were recorded on a Bruker
Avance 250 MHz spectrometer. The 1H-NMR experiments were acquired with a 5 mm BBI z-gradient probe on the 700 MHz Bruker AVANCE III system. For a proton spectrum, 128 transients were used with a 10 µs long 90° pulse and a 12600 Hz spectral width together with a recycling delay of 5 s. The
13
C NMR (176 MHz)
measurements were made with a J-modulated (coupling constant of 145Hz 1H-13C was used) spin-echo for C-nuclei coupled to protons to determine the number of attached protons and proton decoupling during acquisition. The 90° pulse for carbon was 14.5 s long and 16000 scans were taken with a relaxation delay of 2 s. The temperature was regulated at 298.3 K and calibrated with a standard 1H methanol NMR sample using the topspin 3.2 software (Bruker). The control of the temperature was realized with a VTU (variable temperature unit) and an accuracy of +/- 0.1 K. Before Fourier transformation, the data were zero filled to 1024 points in f1 and multiplied by a window function (q-sine bell or sine bell) in both dimension. The spectral widths were 30000 Hz (236 ppm) for 13C and 9000 Hz (18 ppm) for 1H, both nuclei with a relaxation delay of 2.5 s. Proton and carbon spectra were referenced using the solvents signals (DMSO-d5H=2.49 ppm and
13
C: DMSO-d6=39.5 ppm) as
an internal standard. Mass spectra (MS) were obtained using a VG instrument ZAB 2-SE-FPD. UV/Vis absorption spectra were measured on a Lambda 900 spectrometer (Perkin Elmer).
Transmission electron microscopy (TEM) images were measured on a JEOL JEM1400 system. To prepare the TEM samples, a drop of the particle suspension in water was placed onto a 200-mesh copper TEM grid and dried at room temperature. Nitrogen adsorption-desorption isotherms were measured at 77 K on a Micromeritics Tristar II surface area and pore size analyzer. X-ray diffraction (XRD) patterns were recorded on a Fine focus anode system with Cu Kα line (λ=0.15418 nm). Photoisomerization was induced by the LEDs with the wavelengths of 470 and 625 nm (device types LCS-0470-03-22 and LCS-0625-03-22, Mightex Systems). The output intensities of the LEDs were controlled by an LED controller (device type SLC-MA04-MU, Mightex Systems) and were calibrated by an optical powermeter (Model 407A, Spectra-Physics Corporation).
3. Synthesis
Figure S1. Route for the synthesis of 5 (mAzo-Si).
Synthesis of 3 (mAzo-NH2) The synthesis of mAzo-NH2 was as our previous work.1 1
HNMR (DMSO-d6, 250 MHz): δ=7.15 (t, J=8.3 Hz, 1H; Ar-H), δ=6.71 (d, J=8.4 Hz,
2H; Ar-H), δ=5.99 (s, 2H; Ar-NH2), δ=5.94 (s, 2H; Ar-H), δ=3.67 (d, J=1.7 Hz, 12H; -OCH3); 13CNMR (DMSO-d6, 250 MHz): δ=156.1 (Ar-C), δ=153.4 (Ar-C), δ=151.0 (Ar-C), δ=126.6 (Ar-C), δ=123.4 (Ar-C), δ=105.3 (Ar-C), δ=89.9 (Ar-C), δ=55.9 (-OMe), δ=55.4 (-OMe); MS m/z=316.3.
Synthesis of 5 (mAzo-Si) The synthesized 3 (0.032 g, 0.10 mmol) was mixed with 3-ICPES (4 in Figure S1) (0.018 g, 0.11 mmol) in 6 mL of THF. The mixture was heated under reflux and an atmosphere of N2 overnight. After removal of the solvent,
the residue was recrystallized in hexane/THF to get the mAzo-Si. Yield: 78%. 1
HNMR (DMSO-d6, 250 MHz): δ=8.86 (s, 1H; Ar-NH-CO), δ=7.27 (t, J=8.4 Hz, 1H;
Ar-H), δ=6.96 (s, 2H; Ar-H), δ=6.80 (d, J=8.4 Hz, 2H; Ar-H), δ=6.36 (t, J=5.7 Hz, 1H; C-NH-CO), δ=3.83 (t, J=8.4 Hz, 6H; -OCH2-), δ=3.72 (s, 12H; -OCH3), δ=3.14 (q, J=6.6 Hz, 2H; N-CH2-), δ=1.63-1.48 (m, 2H; -CH2-), δ=1.21 (t, J=7.0 Hz, 9H; -CH3), δ=0.70-0.55 (m, 2H; -CH2-Si).
13
CNMR (DMSO-d6, 250 MHz): δ=154.8 (C=O),
δ=153.6 (Ar-C), δ=151.0 (Ar-C), δ=143.5 (Ar-C), δ=134.5 (Ar-C), δ=128.0 (Ar-C), δ=127.1 (Ar-C), δ=105.3 (Ar-C), δ=93.9 (Ar-C), δ=57.7 (-O-CH2), δ=56.0 (-OCH3), δ=55.7 (-OCH3), δ=41.7 (-N-CH2-), δ=23.3 (-CH2-), δ=18.2 (-CH3), δ=7.2 (-CH2-Si).
4. Photoisomerization of mAzo-Si
Figure S2. UV/vis spectra (a) of the mAzo-Si (1.3 mg in 15 mL DMSO) after treating with a sequence of red/blue light (60 mW/cm2, 30 min) and heating (60 oC, 600 min), the absorbance at 340 nm is also showed (b).
5. Synthesis of mesoporous silica nanoparticles (MSNs) The MSNs were synthesized as the reported procedures.1 In a typical synthesis, CTAB (1.000 g, 3.00 mmol) was added to 480 mL of H2O. Then 3.5 mL of NaOH (2 M) aqueous solution was added and induced the complete dissolving of the CTAB. The solution was then heated to 80 °C under stirring. TEOS (5.000 mL, 23.0 mmol) was added to the solution slowly over several minutes, during the adding the precipitate could be observed. The reaction was kept at 80 °C for 2 h under vigorous stirring. Then the solution was filtered while hot using a fritted funnel, the white solid was washed with H2O and MeOH for several times. Then the solid was dried in an oven at 100 °C for over 24h to get the MSNs.
6. Photoresponse of MSNs-Azo
Figure S3. UV/vis spectra of MSNs (5 mg in 1 mL PBS pH=7.4) and MSNs-Azo (5 mg in 1 mL PBS pH=7.4) before and after red and blue light irradiating (60 mW/cm2, 30 min).
7. DOX loading capacity of MSNs-Azo/DOX/CD The loading capacity of the DOX in the nanoparticles was calculated as our previous work.2 After the loading of DOX, the nanoparticles were collected by centrifugation, and the DOX concentration of the residual solution was measured via the UV/vis spectrophotometer. The nanoparticles were washed for three times to remove the adsorbed DOX on surface, and the DOX concentrations in the eluted solutions were measured. The loading capacity of the DOX in the nanoparticles could be calculated by the followed equation:
where LCDOX is the DOX loading capacity (wt. %); m is the weight of the nanoparticles (mg); Cloading, Cresidual, C1, C2 and C3 are the concentrations of the DOX in the original loading solution, residual solution and the eluted solutions for the 1st, 2nd and 3rd time, respectively (mg/mL); Vloading, Vresidual, V1, V2 and V3 are the volumes of the original loading solution, residual solution and the eluted solutions for the 1st, 2nd and 3rd time, respectively (mL).
Figure S4. UV/vis spectra of the eluted solutions for MSNs-Azo/DOX/CD. The DOX loading capacity of the MSNs-Azo/DOX/CD was calculated to be 3.21 wt.%.
8. Red light induced DOX release
Figure S5. UV/vis spectra of the MSNs-Azo/DOX/CD in the dark (a), under 15 mW/cm2 red light (b) and 60 mW/cm2 red light (c) irradiation for different time. UV/vis spectra of the MSNs-Azo/DOX/CD under 15 mW/cm2 red light (d) and 60 mW/cm2 red light (e) irradiation for different time when a piece of tissue was placed between the sample and LED. The amount of released DOX is shown in Fig. 3(b) in the main manuscript.
9. NMR spectra of new compounds
Figure S6. 1HNMR spectrum of the mAzo-Si.
Figure S7. 13CNMR spectrum of the mAzo-Si
Reference 1. Ferris, D.P.; Zhao, Y.-L.; Khashab, N. M.; Khatib, H. A.; Stoddart, J. F.; Zink, J. I. Light-Operated Mechanized Nanoparticles. J. Am. Chem. Soc. 2009, 131, 1686-1688. 2. He, S.; Krippes, K.; Ritz, S.; Chen, Z.; Best, A.; Butt, H.-J.; Mailänder, V.; Wu, S. Ultralow-intensity near-infrared light induces drug delivery by upconverting nanoparticles. Chem. Commun. 2015, 51, 431-434.
