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Peptide-assembled siRNA nanomicelles confine mnox-loaded silicages for synergistic chemical and gene-regulated cancer therapy

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Chinese Chemical Letters 2023年第4期34卷 453-458页

作者： Jingjing Li Juanjuan Wei Yixuan Gao Qi Zhao Jianghui Sun Jin Ouyang Na Na Key Laboratory of Radiopharmaceuticals Ministry of EducationCollege of ChemistryBeijing Normal UniversityBeijing 100085China

Chemodynamic therapy(CDT) is a promising therapeutic approach for in situ cancer treatment, but it is still hindered by inefficient single-modality treatment and the weak targeted delivery of reagents into mitochondria(the main site of intracellular ROS production). Herein, to obtain a multimodal strategy,peptide-assembled si RNA nanomicelles were prepared to confine ultrasmall mnoxin small silica cages(silicages), which is convenient for synergistic chemical and gene-regulated cancer therapy. Given the free energy and versatility of small silicages, as well as the excellent Fenton-like activity of ultrasmall mnox,mnox-inside-loaded silicages(10 nm) were prepared for CDT delivery to mitochondria. Subsequently, to obtain a synergistic CDT and gene silencing treatment, the peptide-mediated assembly of si RNA and mnox-loaded silicages were employed to obtain silicage@mnox-si RNA nanomicelles(SMS NMs). After multiple modifications, sequential cancer cell-targeted delivery, GSH-controlled reagent release of si RNA and mitochondria-targeted delivery of mnox-loaded silicages were successfully achieved. Finally, by both in vitro and in vivo experiments, SMS NMs were confirmed to be effective for synergistic chemical and gene-regulated cancer therapy. Our findings expand the applications of silicages and initiate the development of multimodal CDT.

关键词： Peptide-assembled siRNA nanomicelles mnox-loaded silicages GSH-stimulated release Mitochondria-targeted delivery Cancer therap

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