Photodiagnosis and photodynamic therapy · 2021
VEGF aptamer/i-motif-based drug co-delivery system for combined chemotherapy and photodynamic therapy.
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Zhao Ping, Tang Zi-Wei, Lin Hui-Chao, Djuanda David, Zhu Zhaowei, Niu Qiang, Zhao Li-Min, Qian Yu-Na, Cao Gao, Shen Jian-Liang, Fu Bo
Аннотация
BACKGROUND: Nucleic acids used as drug delivery systems (DDS) have gained attention because of their biosafety and effortless synthesis. G-quadruplex (G4) structured aptamer such as AS1411 was frequently employed to deliver photosensitizers or chemotherapeutic agents while other aptamers were seldomly reported in this field.
METHODS: Herein, a chemical anticancer drug daunomycin (DNM), and a photosensitizer 5, 10, 15, 20-tetra (phenyl-4-N-methyl-4-pyridyl) porphyrin (TMPyP) were physically assembled with a novel DNA structure composed of an aptamer of vascular endothelial growth factor (VEGF) and a cytosine (C)-rich DNA fragment (gc-34). Spectral and molecular mimicking methods were employed to research the drug loading/releasing process. The in vitro cytotoxicity was studied by MTT, ROS, cell cycle, and cell apoptotic assays and the in vivo anticancer efficiency was evaluated by the inhibitive effect on the cancerous growth of MCF-7 tumor-bearing nude mice.
RESULTS: The G4-structured VEGF aptamer delivered TMPyP successfully for the first time. The designed DDS displayed sensitive VEGF/pH controlled drug release. The co-delivery of DNM and TMPyP exhibited high ROS production, significant cell cycle arresting and evident cell apoptosis, and displayed superior cytotoxicity against tumor cells compared with individual agents in vitro. In vivo studies showed that the dual-drug loaded system can greatly inhibit tumor growth with chemotherapeutic/photodynamic synergistic effects.
CONCLUSION: The co-delivery of DNM and TMPyP with aptamer/C-rich DNA successfully integrates the functions of VEGF/pH stimuli-responsive drug release and chemotherapeutic/phototherapeutic modalities into one single system, and may have great potential in cancer treatment.
METHODS: Herein, a chemical anticancer drug daunomycin (DNM), and a photosensitizer 5, 10, 15, 20-tetra (phenyl-4-N-methyl-4-pyridyl) porphyrin (TMPyP) were physically assembled with a novel DNA structure composed of an aptamer of vascular endothelial growth factor (VEGF) and a cytosine (C)-rich DNA fragment (gc-34). Spectral and molecular mimicking methods were employed to research the drug loading/releasing process. The in vitro cytotoxicity was studied by MTT, ROS, cell cycle, and cell apoptotic assays and the in vivo anticancer efficiency was evaluated by the inhibitive effect on the cancerous growth of MCF-7 tumor-bearing nude mice.
RESULTS: The G4-structured VEGF aptamer delivered TMPyP successfully for the first time. The designed DDS displayed sensitive VEGF/pH controlled drug release. The co-delivery of DNM and TMPyP exhibited high ROS production, significant cell cycle arresting and evident cell apoptosis, and displayed superior cytotoxicity against tumor cells compared with individual agents in vitro. In vivo studies showed that the dual-drug loaded system can greatly inhibit tumor growth with chemotherapeutic/photodynamic synergistic effects.
CONCLUSION: The co-delivery of DNM and TMPyP with aptamer/C-rich DNA successfully integrates the functions of VEGF/pH stimuli-responsive drug release and chemotherapeutic/phototherapeutic modalities into one single system, and may have great potential in cancer treatment.