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

Xin Xu; Weijing Yang; Qiujun Liang; Yanan Shi; Wenxin Zhang; Xiao Wang; Fenghua Meng; Zhiyuan Zhong; Lichen Yin

doi:10.1007/s12274-019-2274-2

Nano Research 2019, 12(3): 659-667 https://doi.org/10.1007/s12274-019-2274-2

Research Article | Issue | Published: 09 January 2019

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

Show Author's Information Hide Author's Information Xin Xu^{¹^,^§}, Weijing Yang^{²^,^§}, Qiujun Liang^¹, Yanan Shi^², Wenxin Zhang^¹, Xiao Wang^¹, Fenghua Meng^², Zhiyuan Zhong^²(

), Lichen Yin^¹(

)

1 Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices,Institute of Functional Nano and Soft Materials (FUNSOM), the Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University,Suzhou,215123,China;

2 Biomedical Polymers Laboratory and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application,College of Chemistry, Chemical Engineering and Materials Science, Soochow University,Suzhou,215123,China;

^§Xin Xu and Weijing Yang contributed equally to this work.

Keywords:

ulcerative colitis (UC), anti-inflammatory therapy, polymersomes, reversible crosslinking, siRNA/drug co-delivery, macrophage targeting

Topics:

Controlled drug delivery Cytology Diseases Drug products Macrophages Mammals Sodium compounds Sulfur compounds

Cite this article:

Xu X, Yang W, Liang Q, et al. Efficient and targeted drug/siRNA co-delivery mediated by reversibly crosslinked polymersomes toward anti-inflammatory treatment of ulcerative colitis (UC). Nano Research, 2019, 12(3): 659-667. https://doi.org/10.1007/s12274-019-2274-2

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Abstract

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 crosslinked polymersomes (TKPR-RCP) based on the TKPR-modified, poly(ethylene glycol)-b-poly(trimethylene carbonate-co-dithiolane 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 encapsulation, 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 injection of the co-delivery TKPR-RCP mediated potent 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.

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About this article

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

Show Author's information Hide Author's Information Xin Xu^{¹^,^§}, Weijing Yang^{²^,^§}, Qiujun Liang^¹, Yanan Shi^², Wenxin Zhang^¹, Xiao Wang^¹, Fenghua Meng^², Zhiyuan Zhong^²(

), Lichen Yin^¹(

)

^§Xin Xu and Weijing Yang contributed equally to this work.

Abstract

Keywords: ulcerative colitis (UC), anti-inflammatory therapy, polymersomes, reversible crosslinking, siRNA/drug co-delivery, macrophage targeting

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Acknowledgements

Publication history

Received: 07 November 2018

Revised: 05 December 2018

Accepted: 15 December 2018

Published: 09 January 2019

Issue date: March 2019

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (Nos. 51573123, 51722305, and 51633005), the Ministry of Science and Technology of China (No. 2016YFA0201200), 111 project, and Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).