Folate and lipoic acid functionalized pH/reductive dual-responsive mixed crosslinked micelles for paclitaxel delivery

Feng Minghong; He Teng; Zhao Haiqian; Chen Tao; Lin Wenjing; Yang Chufen

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Folate and lipoic acid functionalized pH/reductive dual-responsive mixed crosslinked micelles for paclitaxel delivery

Updated：2026-08-24

- Folate and lipoic acid functionalized pH/reductive dual-responsive mixed crosslinked micelles for paclitaxel delivery
- Folate and lipoic acid functionalized pH/reductive dual-responsive mixed crosslinked micelles for paclitaxel delivery
- 中国化学工程学报（英文） 2026年94卷第6期页码：102-112
- Affiliations：
  
  School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, China
  Guangdong Provincial Laboratory of Chemistry and Fine Chemical Engineering Jieyang Center, Jieyang 515200, China
- Author bio：
  
  Corresponding authors. E-mail addresses: Wenjing.Lin@gdut.edu.cn(W. Lin)
  cfyang@gdut.edu.cn(C. Yang)
- Funds：
  
  The authors gratefully acknowledge the financial support from the National Natural Science Foundation of China(21676058;21808039);the Guangdong Basic and Applied Basic Research Foundation(2016A030313694;2024A1515011182);the Guangzhou Basic and Applied Basic Research Foundation(2023A04J0064)
- DOI：
  中图分类号：
- 收稿：2025-06-14，
  
  修回：2026-01-05，
  
  录用：2026-01-14，
  
  网络首发：2026-03-10，
  
  纸质出版：2026-06
- Accepted：
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Feng Minghong, He Teng, Zhao Haiqian, 等. Folate and lipoic acid functionalized pH/reductive dual-responsive mixed crosslinked micelles for paclitaxel delivery[J]. 中国化学工程学报（英文）, 2026,94(6):102-112.

Feng Minghong, He Teng, Zhao Haiqian, et al. Folate and lipoic acid functionalized pH/reductive dual-responsive mixed crosslinked micelles for paclitaxel delivery[J]. Chinese Journal of Chemical Engineering, 2026, 94(6): 102-112.
Feng Minghong, He Teng, Zhao Haiqian, 等. Folate and lipoic acid functionalized pH/reductive dual-responsive mixed crosslinked micelles for paclitaxel delivery[J]. 中国化学工程学报（英文）, 2026,94(6):102-112. DOI：

Feng Minghong, He Teng, Zhao Haiqian, et al. Folate and lipoic acid functionalized pH/reductive dual-responsive mixed crosslinked micelles for paclitaxel delivery[J]. Chinese Journal of Chemical Engineering, 2026, 94(6): 102-112. DOI：

摘要

Abstract

To address the challenges of poor stability and weak targeting capability in polymeric micelles

which negatively impact controlled drug release performance

pH-responsive polymers PCL-PDEAEMA-PHEMA-PPEGMA (P1

and P3) with distinct block lengths were designed and synthesized in this work. These copolymers were rigorously characterized using

H NMR

FT-IR

and GPC. Subsequently

polymer P3 was selected for modification based on comparative analyses of critical micelle concentrations (CMC) and drug-loading performance. Polymer P3 underwent esterification with lipoic acid (LA) and folic acid (FA) to yield LA-P3 and FA-P3

respectively. These derivatives were blended at a mass ratio of 1:1 (LA-P3:FA-P3)

and dithiothreitol was employed to initiate self-crosslinking

resulting in the preparation of actively targeted crosslinked mixed micelles (C-MIX). The results revealed that C-MIX@PTX drug-loaded micelles prepared at a feeding ratio of 15 mg PTX/30 mg polymer exhibited a smaller size (134.7 nm) compared to non-crosslinked micelles

with a drug-loading content of 15.31% ±1.79% and an encapsulation efficiency of 38.42% ±5.22%.

In vitro

release studies demonstrated that under neutral conditions

C-MIX@PTXachieved a cumulative drug release of 16.8% at 120 h

significantly lower than non-crosslinked micelles. Under acidic/reductive conditions

C-MIX@PTX showed a cumulative drug release of 77.1% at 120 h

slightly lower compared to non-crosslinked micelles. Cytotoxicity assays confirmed that both MIX and C-MIX were biocompatible low-toxicity carrier materials

whileLA-P3@PTX

FA-P3@PTX

MIX@PTX

and C-MIX@PTX exhibited inhibitory effects on HepG2 cells

FA-P3@PTX with folate-modified demonstrated enhanced efficacy.

关键词

Keywords

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