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Theranostics ; 8(16): 4332-4344, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30214624

RESUMO

Photodynamic therapy (PDT) has been applied in clinical cancer treatment. Here we report an aptamer-functionalized nanoscale metal-organic framework for targeted PDT. Our nanosystem can be easily prepared and successfully used for targeted PDT with a significantly enhanced therapeutic efficacy in vitro and in vivo. Methods: By combining the strong binding ability between phosphate-terminated aptamers and Zr-based nanoscale metal-organic frameworks (Zr-NMOFs) and the intercalation of photosensitizer TMPyP4 within the G-quadruplex DNA structure, TMPyP4-G4-aptamer-NMOFs were prepared. The characteristics and photodynamic performance of TMPyP4-G4-aptamer-NMOFs were examined after preparation. Then, we studied their stability, specific recognition ability, and phototoxicity in vitro. For in vivo experiments, the nanosystem was intratumorally injected into a HeLa subcutaneous xenograft tumor mouse model. After irradiation on day 0, mice were further injected with the nanosystem on day 5 and were again subjected to laser irradiation for 30 min. Tumor volumes and body weights of all mice were measured by caliper every 2 days after the treatment. Results: The nanosystem induced 90% cell death of targeted cells. In contrast, the control cells maintained about 40% cell viability at the same concentration of nanosystem. For the in vivo experiments, the nanosystem-treated group maintained more than 76% inhibition within the entire experimental period. Conclusion: We have demonstrated that our smart TMPyP4-G4-sgc8-NMOFs nanosystem can be used for targeted cancer therapy with high efficiency.


Assuntos
Aptâmeros de Nucleotídeos/administração & dosagem , Quadruplex G , Estruturas Metalorgânicas/administração & dosagem , Terapia de Alvo Molecular/métodos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Porfirinas/administração & dosagem , Animais , Aptâmeros de Nucleotídeos/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Portadores de Fármacos/administração & dosagem , Estabilidade de Medicamentos , Células HeLa , Xenoenxertos , Humanos , Estruturas Metalorgânicas/toxicidade , Camundongos , Transplante de Neoplasias , Neoplasias Experimentais/patologia , Neoplasias Experimentais/terapia , Fármacos Fotossensibilizantes/toxicidade , Porfirinas/toxicidade , Resultado do Tratamento
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