期刊
JOURNAL OF CONTROLLED RELEASE
卷 344, 期 -, 页码 97-112出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2022.02.022
关键词
Controlled release; mRNA gene therapy; siRNA gene therapy; Hydrogel; Tumor microenvironment
资金
- Key Research and Development Program of Science and Technology Department of Sichuan Province [2020YFS0200]
- National Natural Science Foundation [82003258]
- Scientific Research Program of Health Commission of Sichuan Province [20PJ097]
- Science Foundation of Chengdu [2019-YF05-00639-SN]
This study developed a novel drug release system that can control the release of siRNA and mRNA, protect these nucleic acids from biodegradation, and activate the immune response to effectively inhibit tumor growth. This research provides a valuable tool for cancer gene therapy.
Drug-controlled release is recognized as effective for improving compliance with treatment and obtaining better therapeutic efficacy with less toxicity in cancer treatment. However, few reports in this area are involved in nucleic acids delivery, especially in RNA therapeutics delivery. In this study, an injectable hydrogel Methacry-lated gelatin (GM) scaffold was introduced into a dual-RNA hybrid delivery complex hybrid lipid particle (HLP) to form a G-HLP/RNAs system. This system can control the release of both siRNA and mRNA and was found to be efficient for protecting these RNAs from biodegradation and retaining their therapeutic effect over 7 days. Further, a tumor environment (TME)-activation function after peritumoral injection of mocked GM scaffold was observed. Then, matured DC cells and activated T-cells were detected by the addition of HLP/RNAs complex, thus verifying the immunoactivation function of GM scaffold and its ability to reserve immune cells and antigens. Finally, two doses of G-HLP/RNAs treatment efficiently suppressed C26 tumor growth in mice with a tumor weight inhibition rate of 71.9%. Owing to its ability to achieve RNA drug-controlled release, alter TME, and induce tumor apoptosis, the G-HLP/RNAs system may become a valuable tool for cancer gene therapy.
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