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• W3112028278 abstract "Selective intracellular transportation of RNA interference (RNAi) into the cytosol of tumor cells is deemed as an intriguing strategy for treatment of intractable tumors. Pertaining to sequential biological barriers, polymeric RNAi therapeutics were engineered by covalent conjugation of multiple small interference RNA (siRNA) molecules onto a polylysine (PLys) segment of cyclic Arg-Gly-Asp (RGD)-poly(ethylene glycol)-block-PLys [RGD-PEG-PLys(siRNA)] through a redox-responsive disulfide linkage. Furthermore, the constructed polyanionic siRNA conjugates were designed to precipitate with inorganic CaPO3 (CaP) for manufacturing siRNA delivery nanoassemblies. The subsequent investigations validated their appreciable colloidal stability in physiological conditions. Moreover, the RGD ligand facilitated cellular endocytosis in cancerous cells, and internalized nanoassemblies could readily dissociate in the acidic endosomal microenvironment due to CaP dissolution. Simultaneously, the elevated osmotic pressure owing to CaP dissolution provoked disruption of endosomes, thereby accounting for release of RGD-PEG-PLys(siRNA) into the cytosol. Eventually, the disulfide linkage in RGD-PEG-PLys(siRNA) could cleave in the reducing cytoplasmic microenvironment, eliciting siRNA liberation for RNAi. Ultimately, the proposed siRNA constructs, attempting to encapsulate antiangiogenic RNAi payloads, exhibited potent in vivo RNAi to the targeted glioma cells and antitumor efficacy via systemic administration." @default.
• W3112028278 created "2020-12-21" @default.
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• W3112028278 date "2020-12-10" @default.
• W3112028278 modified "2023-10-04" @default.
• W3112028278 title "Tumor-Targeted Anti-VEGF RNAi Capable of Sequentially Responding to Intracellular Microenvironments for Potent Systemic Tumor Suppression" @default.
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• W3112028278 doi "https://doi.org/10.1021/acsabm.0c01427" @default.
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