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Size- and Surface- Dual Engineered Small Polyplexes for Efficiently Targeting Delivery of siRNA
Shuang Liu1,2, Shaohui Deng1, Xiaoxia Li1
1PCFM Lab of Ministry of Education & Guangzhou Key Laboratory of Flexible Electronic Materials and Wearable Devices, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510275, China.
Molecules (Basel, Switzerland)
|June 2, 2021
Summary
This study developed a novel copolymer for efficient small interfering RNA (siRNA) delivery. The engineered polyplexes show controlled size reduction and enhanced cellular uptake for targeted therapy.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Drug Delivery
Background:
- Efficient delivery of small interfering RNA (siRNA) is crucial for RNA interference (RNAi) therapies but remains a significant challenge.
- Current delivery systems often struggle with stability, targeting, and cellular uptake.
Purpose of the Study:
- To design and synthesize a novel copolymer for creating advanced siRNA polyplexes.
- To engineer polyplex size and surface properties for improved siRNA delivery, circulation time, and targeting.
Main Methods:
- Synthesis of a multi-block copolymer: PAsp(-N=C-PEG)-PCys-PAsp(DETA).
- Formation of siRNA polyplexes with a pH-sensitive outer layer, crosslinked interlayer, and complexing core.
- Investigated pH-triggered PEG shedding and disulfide bond crosslinking for size reduction.
- Surface modification with an anionic copolymer and lauric acid for charge neutralization and targeting.
Main Results:
- The synthesized copolymer formed stable siRNA polyplexes with a unique sandwich-like structure.
- pH-triggered imine bond cleavage led to PEG shedding, and disulfide crosslinking reduced polyplex size from 75 nm to 26 nm.
- Surface modification enhanced transfection efficiency and lysosomal escape capacity.
Conclusions:
- The developed strategy enables precise engineering of polyplex size and surface characteristics.
- These modified polyplexes offer a promising platform for long blood circulation and targeted delivery of siRNA in therapeutic applications.
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