Citation: Changgui Tong, Yan Zhao, Sheng Lin, Yong Zhang, Qixian Chen, Yue Wang. Augmenting stealth attributes and intracellular trafficking of polyplex micelles via charge-switching corona for superior gene transduction[J]. Chinese Chemical Letters, ;2025, 36(10): 110796. doi: 10.1016/j.cclet.2024.110796 shu

Augmenting stealth attributes and intracellular trafficking of polyplex micelles via charge-switching corona for superior gene transduction

Changgui Tong ^a ,
Yan Zhao ^{b, c, d} ,
Sheng Lin ^e ,
Yong Zhang ^e ,
Qixian Chen ^{b, d, f, g, h, *,} ,
Yue Wang ^{b, c, d, *,}

a.
Department of Hand and Foot Microsurgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China
b.
Department of Gastric Surgery, Cancer Hospital of Dalian University of Technology, Shenyang 110042, China
c.
Department of Gastric Surgery, Cancer Hospital of China Medical University, Shenyang 110042, China
d.
Provincial Key Laboratory of Interdisciplinary Medical Engineering for Gastrointestinal Carcinoma, Liaoning Cancer Hospital & Institute, Shenyang 110042, China
e.
The State Key Laboratory of Molecular Engineering of Polymers and Department of Macromolecular Science, Fudan University, Shanghai 200433, China
f.
School of Bioengineering, Dalian University of Technology, Dalian 116024, China
g.
Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518120, China
h.
Innovation Center of Yangtze River Delta, Zhejiang University, Jiaxing 314100, China

plasmid@zju.edu.cn

wangyue3@cancerhosp-ln-cmu.com

Received Date: 5 November 2024
Revised Date: 20 December 2024
Accepted Date: 23 December 2024
Available Online: 31 January 2025

Figures(4)

The surface physiochemical features of nanomedicine are essential for controlling biointerfacial interactions in biological compartments and achieving the programmed delivery scenario to intracellular targets. This work presents a novel dynamic triple-transformable surface engineering strategy that can adapt to sequential variable biological microenvironments and intelligently managing the previously acknowledged biological obstacles. By employing click chemistry, the surface of a classical PEGylated pDNA delivery nanoparticles were tethered with a multiple of charge-reversible polymers to endow the dynamic biointerfacial surroundings. Crucially, the dynamic surroundings had negative charge under physiological circumstances (pH 7.4), which inhibited structural disintegration brought on by charged biological species and anionic nuclease degradation. In addition, by regulating the first pass effect, the nanoparticles demonstrated appreciable stealth function that led to persistent systemic retention and improved bioavailability and consistent internalization into the targeted cells. In subsequence to cell endocytosis, translocation from the digestive endolysosomes to the targeted cytosol was facilitated due to acidification (endosomal pH 5.5) of the dynamic surroundings into highly positive charge, consequently leading to explosive disruptive effects on the endolysosomal structures and retrieve the bio-vulnerable pDNA payloads. In conclusion, our proposed unique dynamic surface chemistry provides a viable delivery mechanism that successfully navigates a series of biological roadblocks and collaborates to effectively express the encapsulated pDNA at the targeted cells.
- pDNA,
- Nanomedicine,
- Dynamic surface chemistry,
- Charge reversal,
- Endolysosomes
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