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bio-assembled smart nanocapsules for targeted delivery of KRAS shRNA and cancer cell bioimage

Chinese Chemical Letters 2023年第1期34卷 270-273页

作者： Maonan Wang Zengchao Guo Jiayu Zeng Liu Liu Yihan Wang Jinpeng Wang Hongbing Lu Haijun Zhang Hui Jiang Xuemei Wang State Key Laboratory of bioelectronics(Chien-Shiung Wu Lab) School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China Department of biomedical Engineering/Computer Application Fourth Military Medical UniversityXi’an 710032China Department of Oncology Zhongda HospitalMedical School of Southeast UniversityNanjing 210009China

The five-year survival rate for pancreatic cancer is less than 5%. However, the current clinical multimodal therapy combined with first-line chemotherapy drugs only increases the patient’s median survival from 5.0 months to 7.2 months. Consequently, a new strategy of cancer treatments is urgently needed to overcome this high-fatality disease. Through a series of biometric analyses, we found that KRAS is highly expressed in the tumor of pancreatic cancer patients, and this high expression is closely related to the poor prognosis of patients. It shows that inhibiting the expression of KRAS has great potential in gene therapy for pancreatic cancer. Given those above, we have exploited the possibility of targeted delivery of KRAS shRNA with the intelligent and bio-responsive nanomedicine to detect the special oxidative stress microenvironment of cancer cells and realize efficient cancer theranostics. Our observations demonstrate that by designing the smart self-assembled nanocapsules of melanin with fluorescent nanoclusters we can readily achieve the bio-recognition and bioimaging of cancer cells in biological solution or *** self-assembled nanocapsules can make a significant bio-response to the oxidative stress microenvironment of cancer cells and generate fluorescent zinc oxide Nanoclusters in situ for targeted cell bioimaging. Moreover, it can also readily facilitate cancer cell suppression through the targeted delivery of KRAS shRNA and low-temperature hyperthermia. This raises the possibility to provide a promising theranostics platform and self-assembled nanomedicine for targeted cancer diagnostics and treatments through special oxidative stress-responsive effects of cancer cells.

关键词： smart bio-responsive nanocapsules Intelligent nanomedicine shRNA KRAS Fluorescent bioimaging Oxidative stress response

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