Design of Reduction-Responsive Copolymer-Based Nanoparticles for Enhanced Anticancer Drug Delivery

IF 4.7 3区 工程技术 Q2 ENGINEERING, ENVIRONMENTAL Journal of Polymers and the Environment Pub Date : 2024-09-16 DOI:10.1007/s10924-024-03403-5
Haotian Hu, Hongjing Liu, Qingqing Li, Yongpeng Shen, Jialin Lu, Xiaowen Liu, Yu Tong, Yiheng Feng, Qingbo Xu, Yuxiang Tang, Jing Chu, Hang Hu, Tianyu Zhu, Defeng Xu
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Abstract

Polymer-based nanoparticles with tumor-targeting ability, controlled-release properties and good biocompatibility are of great interest for anticancer drug delivery. Herein, two amphiphilic reduction-responsive copolymers self-assembled nanoparticles (mPEG-Cys-PCL and mPEG-Ami-PCL) along with their inert counterpart (mPEG-Hex-PCL) were prepared and evaluated. These three copolymers were synthesized by conjugating mPEG and PCL with different linkers and characterized by proton nuclear magnetic resonance spectrometry, flourier transform infrared spectrometry and gel permeation chromatography. Nile red (NR) was loaded into the prepared nanoparticles as a model drug to study the in vitro drug release, cellular uptake amount and biodistribution. Dimethylcurcumin (DMC) was loaded into the prepared nanoparticles to study the in vitro antitumor effect. The results show that NR@mPEG-Cys-PCL and NR@mPEG-Ami-PCL nanoparticles exhibit glutathione (GSH)-triggered drug release and NR@mPEG-Ami-PCL nanoparticles display enhanced GSH-responsiveness as compared to NR@mPEG-Cys-PCL. Moreover, NR@mPEG-Ami-PCL nanoparticles possess enhanced cellular uptake amount as compared to NR@mPEG-Hex-PCL and NR@mPEG-Cys-PCL nanoparticles. DMC@mPEG-Ami-PCL nanoparticles possess the highest in vitro antitumor effect. In biodistribution study, both NR@mPEG-Cys-PCL and NR@mPEG-Ami-PCL nanoparticles show reduced organ distribution and similar tumor accumulation as compared to NR@mPEG-Hex-PCL nanoparticles. The mPEG-Ami-PCL nanoparticles developed in this work show great potential for anticancer drug delivery.

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设计基于还原反应共聚物的纳米颗粒以增强抗癌药物的输送
具有肿瘤靶向能力、可控释放特性和良好生物相容性的聚合物基纳米粒子在抗癌药物递送方面备受关注。本文制备并评估了两种两亲还原反应共聚物自组装纳米粒子(mPEG-Cys-PCL 和 mPEG-Ami-PCL)及其惰性对应物(mPEG-Hex-PCL)。这三种共聚物是通过将 mPEG 和 PCL 与不同的连接剂共轭而合成的,并通过质子核磁共振光谱法、傅立叶变换红外光谱法和凝胶渗透色谱法进行了表征。将尼罗红(NR)作为模型药物载入所制备的纳米颗粒,研究其体外药物释放、细胞摄取量和生物分布。将二甲基姜黄素(DMC)加入制备的纳米颗粒中,研究其体外抗肿瘤效果。结果表明,与 NR@mPEG-Cys-PCL 相比,NR@mPEG-Cys-PCL 和 NR@mPEG-Ami-PCL 纳米颗粒表现出谷胱甘肽(GSH)触发的药物释放,NR@mPEG-Ami-PCL 纳米颗粒表现出更强的 GSH 反应性。此外,与 NR@mPEG-Hex-PCL 和 NR@mPEG-Cys-PCL 纳米颗粒相比,NR@mPEG-Ami-PCL 纳米颗粒具有更高的细胞吸收量。DMC@mPEG-Ami-PCL纳米颗粒的体外抗肿瘤效果最好。在生物分布研究中,与NR@mPEG-Hex-PCL纳米颗粒相比,NR@mPEG-Cys-PCL和NR@mPEG-Ami-PCL纳米颗粒的器官分布减少,肿瘤蓄积相似。本研究开发的mPEG-Ami-PCL纳米颗粒在抗癌药物递送方面显示出巨大的潜力。
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来源期刊
Journal of Polymers and the Environment
Journal of Polymers and the Environment 工程技术-高分子科学
CiteScore
9.50
自引率
7.50%
发文量
297
审稿时长
9 months
期刊介绍: The Journal of Polymers and the Environment fills the need for an international forum in this diverse and rapidly expanding field. The journal serves a crucial role for the publication of information from a wide range of disciplines and is a central outlet for the publication of high-quality peer-reviewed original papers, review articles and short communications. The journal is intentionally interdisciplinary in regard to contributions and covers the following subjects - polymers, environmentally degradable polymers, and degradation pathways: biological, photochemical, oxidative and hydrolytic; new environmental materials: derived by chemical and biosynthetic routes; environmental blends and composites; developments in processing and reactive processing of environmental polymers; characterization of environmental materials: mechanical, physical, thermal, rheological, morphological, and others; recyclable polymers and plastics recycling environmental testing: in-laboratory simulations, outdoor exposures, and standardization of methodologies; environmental fate: end products and intermediates of biodegradation; microbiology and enzymology of polymer biodegradation; solid-waste management and public legislation specific to environmental polymers; and other related topics.
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