Flash Nanoprecipitation Fabrication of Chitosan/Sodium Tripolyphosphate Nanoparticles for siRNA Delivery

FENG Jing-ye; HUANG Wen-wu; ZHAN Qing-yi; YAN Yun-feng; WU Cheng-fan

doi:10.14028/j.cnki.1003-3726.2025.24.304

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Flash Nanoprecipitation Fabrication of Chitosan/Sodium Tripolyphosphate Nanoparticles for siRNA Delivery

更新时间：2025-02-27

- Flash Nanoprecipitation Fabrication of Chitosan/Sodium Tripolyphosphate Nanoparticles for siRNA Delivery
- Polymer Bulletin Vol. 38, Issue 3, Pages: 460-471(2025)
- 作者机构：
  
  浙江工业大学生物工程学院，杭州 310000
- 作者简介：
- 基金信息：
- DOI：10.14028/j.cnki.1003-3726.2025.24.304
  CLC：
- Received：10 October 2024，
  
  Accepted：2024-12-09，
  
  Published Online：27 January 2025，
  
  Published：20 March 2025
- 稿件说明：
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冯晶烨, 黄文武, 詹青怡, 燕云峰, 吴澄帆. 瞬时纳米沉淀法制备壳聚糖/三聚磷酸钠纳米粒子及其siRNA递送性能评价. 高分子通报, 2025, 38(3), 460–471.

Feng, J. Y.; Huang, W. W.; Zhan, Q. Y.; Yan, Y. F.; Wu, C. F. Flash nanoprecipitation fabrication of chitosan/sodium tripolyphosphate nanoparticles for siRNA delivery. Polym. Bull. (in Chinese), 2025, 38(3), 460–471.
冯晶烨, 黄文武, 詹青怡, 燕云峰, 吴澄帆. 瞬时纳米沉淀法制备壳聚糖/三聚磷酸钠纳米粒子及其siRNA递送性能评价. 高分子通报, 2025, 38(3), 460–471. DOI： 10.14028/j.cnki.1003-3726.2025.24.304.

Feng, J. Y.; Huang, W. W.; Zhan, Q. Y.; Yan, Y. F.; Wu, C. F. Flash nanoprecipitation fabrication of chitosan/sodium tripolyphosphate nanoparticles for siRNA delivery. Polym. Bull. (in Chinese), 2025, 38(3), 460–471. DOI： 10.14028/j.cnki.1003-3726.2025.24.304.

摘要

RNA干扰在癌症和其他多种疾病的治疗中具有广阔的应用前景，亟需发展高效、安全的递送手段来实现RNA干扰技术的临床应用。本研究使用瞬时纳米沉淀技术，制备系列稳定的、基于壳聚糖(CS)和三聚磷酸钠(TPP)的纳米粒子，系统研究了CS浓度、分子量及其与TPP的质量比对CS/TPP纳米粒子的物理化学性质的影响，并初步评价了纳米粒子的基因沉默效率。结果显示，CS浓度为0.3~0.6 g/L和CS/TPP质比为1/1~4/1时，可以形成较为稳定的复合物。其中，CS浓度为0.5 g/L，质量比为2/1时可得到直径为70~100 nm的稳定纳米粒子。稳定的CS/TPP纳米粒子对siRNA的负载效率为75%~90%，细胞毒性低。在2.5 ng siRNA/μL浓度下，负载siRNA的CS/TPP纳米粒子可以引起约30%的目的基因的沉默。相关结果对制备稳定的、小尺寸CS纳米粒子及其 siRNA递送研究具有一定的借鉴意义。

Abstract

RNA interference (RNAi) holds great potential in the treatment of cancer and various diseases. It is urgent to develop efficient and safe delivery carriers to achieve the clinical application of RNAi-based therapeutics. In this study

Flash nanoprecipitation (FNP) technology was utilized to prepare stable nanoparticles (NPs) based on CS and sodium tripolyphosphate (TPP). The effects of chitosan (CS) concentration

molecular weight

and the mass ratio of CS to TPP on the physicochemical properties of CS/TPP NPs were extensively investigated. Subsequently

suitable NPs were selected for

in vitro

siRNA delivery to HeLa cells. The results showed that stable complex NPs could be formed when the concentration of CS was 0.3-0.6 g/L and the mass ratio of CS to TPP was 1/1-4/1. Among them

stable CS NPs with a diameter of 70-100 nm were obtained at a CS concentration of 0.5 g/L and a CS/TPP mass ratio of 2/1. The selected CS/TPP NPs demonstrated a siRNA loading efficiency of 75%-90% with low cytotoxicity. siRNA-loaded CS NPs induced approximately 30% silencing of the target gene at a siRNA dose of 2.5 ng/μL

indicating a certain level of siRNA delivery efficiency. These results provide valuable insights for preparing stable and small CS NPs for siRNA delivery.

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