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Efficient and targeted drug/siRNA co-delivery mediated by reversibly crosslinked polymersomes toward anti-inflammatory treatment of ulcerative colitis (UC) 被引量:4

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摘要 Co-delivery of anti-inflammatory siRNA and hydrophilic drug provides a promising approach for the treatment of ulcerative colitis (UC). However, lack of a suitable and efficient co-delivery carrier poses critical challenge against their utilization. We herein developed macrophage-targeting, reversibly crossli nked polymersomes (TKPR-RCP) based on the TKPR-modified, poly(ethyle ne glycol)-b-poly(trimethylene carbonate-codithiolane trimethylene carbonate)-b-polyethylenimine (PEG-P(TMC-DTC)-PEI) triblock copolymer, which could efficiently encapsulate TNF-α siRNA and dexamethasone sodium phosphate (DSP) in their hydrophilic core. The cationic PEI segments provided additional electrostatic interactions with cargo molecules to promote the encapsulatiion, and disulfide crosslinking of the polymersome membrane endowed the TKPR-RCP with high colloidal stability. Because the cationic PEI was embedded in the hydrophilic core, the polymersomes displayed neutral surface charge and thus possessed high serum stability. The TKPR-RCP co-encapsulating TNF-α siRNA and DSP could be efficiently internalized by macrophages (~98%) and undergo redox-responsive membrane de-crosslinking to accelerate cargo release in the cytoplasm, thus inducing efficient gene silencing and anti-inflammatory effect .Intravenous injectio n of the co-delivery TKPR-RCP mediated pote nt and cooperative anti-inflammatory effect in inflamed colons of UC mice, and significantly prevented animals from colonic injury. This study therefore provides a promising approach for the co-delivery of hydrophilic drug/siRNA toward the treatment of inflammatory bowel diseases.
出处 《Nano Research》 SCIE EI CAS CSCD 2019年第3期659-667,共9页 纳米研究(英文版)
基金 National Natural Science Foundation of China (Nos. 51573123, 51722305, and 51633005) the Ministry of Science and Technology of China (No. 2016YFA0201200) 111 project Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).
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