A multifunctional drug delivery system（GNRs@mSiO_2-HA-RGD） was developed by conjugating targeting ligand hyaluronic acid（HA） and RGD with mesoporous silica-coated gold nanorods（GNRs@mSiO_2） for dual-targeted che...A multifunctional drug delivery system（GNRs@mSiO_2-HA-RGD） was developed by conjugating targeting ligand hyaluronic acid（HA） and RGD with mesoporous silica-coated gold nanorods（GNRs@mSiO_2） for dual-targeted chemo-photothermal therapy. The physiochemical properties of the prepared nanoparticles were characterized by FTIR, UV-vis spectra, and ~1H NMR. Doxorubicin hydrochloride（DOX）, an anticancer drug, was used as the model drug to investigate the drug loading, in vitro drug release profiles and cytotoxicity. The experimental results show that DOX-GNRs@mSiO_2-HA-RGD is synthesized with a mean diameter of 116 nm and a sufficient load capacity of about 19.8%. It also has p H-enzyme sensitive and NIRtriggered drug release manner. Cellular uptake indicates that DOX-GNRs@mSiO_2-HA-RGD exhibits a higher cellular uptake via CD44 receptor and integrin receptor mediated endocytosis compared with the GNRs@mSiO_2 modified with one receptor or no receptor. In comparison with chemotherapy or photothermal therapy alone, DOX-GNRs@mSiO_2-HA-RGD displayes the synergistic effects and achieves a higher therapeutic efficacy. It can be expected that DOX-GNRs@mSiO_2-HA-RGD is a potential dual-targeted chemo-photothermal therapeutic platform for effective cancer treatment.展开更多
Multispectral optoacoustic tomography （MSOT） is an emerging imaging technology that offers several advantages over traditional modalities, particularly in its ability to resolve optical contrast at depth on the micr...Multispectral optoacoustic tomography （MSOT） is an emerging imaging technology that offers several advantages over traditional modalities, particularly in its ability to resolve optical contrast at depth on the microscopic scale. While potential applications include the early detection of tumors below clinical thresholds set by current technology, the lack of tumor-specific contrast agents limits the use of MSOT imaging. Therefore, we constructed highly stable nano-contrast agents by coating gold nanorods （GNRs） with either polyacrylic acid （PAA） or amine- functionalized mesoporous silica （MS）. Syndecan-1, which has been shown to target insulin-like growth factor 1 receptor （IGF1-R） （upregulated in pancreatic tumors）, was conjugated on the surface of PAA-coated GNRs （PAA-GNRs） or MS-coated GNRs （MS-GNRs） to create tumor-targeted nanoparticles. In vitro, tumor targeting of nanoparticles was assessed with flow cytometry. In S2VP10L cells （positive for IGF1-R）, the syndecan-1 MS-GNRs （Syndecan-MS-GNRs） demonstrated an increase in OA signal, 10x, compared to syndecan-1 PAA- GNRs （Syndecan-PAA-GNRs）. Minimal binding was observed in MiaPaca-2 cells （negative for IGF1-R）. In vivo, tumor specific targeting of Syndecan-MS-GNRs was evaluated using a murine orthotopic pancreatic cancer model. The Syndecan- MS-GNRs demonstrated significantly greater accumulation within pancreatic tumors than in off-target organs such as the liver. Mice implanted with the IGF1-R negative MiaPaca-2 cells did not demonstrate specific tumor targeting. In summary, we report that targeted nano-contrast agents （Syndecan-MS-GNRs） can successfully detect orthotopic pancreatic tumors with minimum off-target binding in vivo using MSOT.展开更多
Nanocomposites （NCs） consisting of a gold nanorod core and a mesoporous silica shell doped with hematoporphyrin （HP） have been fabricated in order to improve the efficiency of cancer treatment by combining phototh...Nanocomposites （NCs） consisting of a gold nanorod core and a mesoporous silica shell doped with hematoporphyrin （HP） have been fabricated in order to improve the efficiency of cancer treatment by combining photothermal and photodynamic therapies （PDT ＋ PTT） in vivo. In addition to the long-wavelength plasmon resonance near 810-830 nm, the fabricated NCs exhibited a 400-nm absorbance peak corresponding to bound HP, generated singlet oxygen under 633-nm excitation near the 632.5-nm Q-band, and produced heat under a 808-nm near-infrared （NIR） laser irradiation. These modalities were used for a combined PDT ＋ PTT treatment of large （about 3 cm3） solid tumors in vivo with a xenorafted tumor rat model. NCs were directly injected into tumors and irradiated simultaneously with 633-nm and 808-nm lasers to stimulate the combined photodynamic and photothermal activities of NCs. The efficiency of the combined therapy was evaluated by optical coherence tomography, histological analysis, and by measurements of the tumor volume growth during a 21-day period. The NC-mediated PDT led to weak changes in tissue histology and to a moderate 20% decrease in the tumor volume. In contrast, the combined PDT ＋ PTT treatment resulted in the large-area tumor necrosis and led to dramatic decrease in the tumor volume.展开更多
基金Funded by the National Natural Science Foundation of China(Nos.51473130 and 51572206)the Wuhan Huanghe excellence plan and Entrepreneurship Training Program of Wuhan University and Technology(Nos.20171049720018,20171049720019,and 20171049720009)
文摘A multifunctional drug delivery system（GNRs@mSiO_2-HA-RGD） was developed by conjugating targeting ligand hyaluronic acid（HA） and RGD with mesoporous silica-coated gold nanorods（GNRs@mSiO_2） for dual-targeted chemo-photothermal therapy. The physiochemical properties of the prepared nanoparticles were characterized by FTIR, UV-vis spectra, and ~1H NMR. Doxorubicin hydrochloride（DOX）, an anticancer drug, was used as the model drug to investigate the drug loading, in vitro drug release profiles and cytotoxicity. The experimental results show that DOX-GNRs@mSiO_2-HA-RGD is synthesized with a mean diameter of 116 nm and a sufficient load capacity of about 19.8%. It also has p H-enzyme sensitive and NIRtriggered drug release manner. Cellular uptake indicates that DOX-GNRs@mSiO_2-HA-RGD exhibits a higher cellular uptake via CD44 receptor and integrin receptor mediated endocytosis compared with the GNRs@mSiO_2 modified with one receptor or no receptor. In comparison with chemotherapy or photothermal therapy alone, DOX-GNRs@mSiO_2-HA-RGD displayes the synergistic effects and achieves a higher therapeutic efficacy. It can be expected that DOX-GNRs@mSiO_2-HA-RGD is a potential dual-targeted chemo-photothermal therapeutic platform for effective cancer treatment.
文摘Multispectral optoacoustic tomography （MSOT） is an emerging imaging technology that offers several advantages over traditional modalities, particularly in its ability to resolve optical contrast at depth on the microscopic scale. While potential applications include the early detection of tumors below clinical thresholds set by current technology, the lack of tumor-specific contrast agents limits the use of MSOT imaging. Therefore, we constructed highly stable nano-contrast agents by coating gold nanorods （GNRs） with either polyacrylic acid （PAA） or amine- functionalized mesoporous silica （MS）. Syndecan-1, which has been shown to target insulin-like growth factor 1 receptor （IGF1-R） （upregulated in pancreatic tumors）, was conjugated on the surface of PAA-coated GNRs （PAA-GNRs） or MS-coated GNRs （MS-GNRs） to create tumor-targeted nanoparticles. In vitro, tumor targeting of nanoparticles was assessed with flow cytometry. In S2VP10L cells （positive for IGF1-R）, the syndecan-1 MS-GNRs （Syndecan-MS-GNRs） demonstrated an increase in OA signal, 10x, compared to syndecan-1 PAA- GNRs （Syndecan-PAA-GNRs）. Minimal binding was observed in MiaPaca-2 cells （negative for IGF1-R）. In vivo, tumor specific targeting of Syndecan-MS-GNRs was evaluated using a murine orthotopic pancreatic cancer model. The Syndecan- MS-GNRs demonstrated significantly greater accumulation within pancreatic tumors than in off-target organs such as the liver. Mice implanted with the IGF1-R negative MiaPaca-2 cells did not demonstrate specific tumor targeting. In summary, we report that targeted nano-contrast agents （Syndecan-MS-GNRs） can successfully detect orthotopic pancreatic tumors with minimum off-target binding in vivo using MSOT.
文摘Nanocomposites （NCs） consisting of a gold nanorod core and a mesoporous silica shell doped with hematoporphyrin （HP） have been fabricated in order to improve the efficiency of cancer treatment by combining photothermal and photodynamic therapies （PDT ＋ PTT） in vivo. In addition to the long-wavelength plasmon resonance near 810-830 nm, the fabricated NCs exhibited a 400-nm absorbance peak corresponding to bound HP, generated singlet oxygen under 633-nm excitation near the 632.5-nm Q-band, and produced heat under a 808-nm near-infrared （NIR） laser irradiation. These modalities were used for a combined PDT ＋ PTT treatment of large （about 3 cm3） solid tumors in vivo with a xenorafted tumor rat model. NCs were directly injected into tumors and irradiated simultaneously with 633-nm and 808-nm lasers to stimulate the combined photodynamic and photothermal activities of NCs. The efficiency of the combined therapy was evaluated by optical coherence tomography, histological analysis, and by measurements of the tumor volume growth during a 21-day period. The NC-mediated PDT led to weak changes in tissue histology and to a moderate 20% decrease in the tumor volume. In contrast, the combined PDT ＋ PTT treatment resulted in the large-area tumor necrosis and led to dramatic decrease in the tumor volume.
