Stimuli-responsive self-assembly and colloidal properties of hyaluronic acid-poly (ethylene glycol)-poly(ε-caprolactone) (HA-PEG-PCL) amphiphilic triblock copolymers for cancer nanotherapy

IF 2.9 4区化学 Q3 CHEMISTRY, PHYSICAL

Colloid and Polymer Science Pub Date : 2026-05-01 DOI:10.1007/s00396-026-05626-5

Kunal Ravindra Talele, Sankha Bhattacharya

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Abstract

The Hyaluronic Acid-Poly (ethylene glycol)-Poly(ε-caprolactone) (HA-PEG-PCL) amphiphilic triblock copolymers function as multifunctional nanocarriers which deliver cancer treatment through their active targeting capacity and prolonged bloodstream presence and ability to release drugs upon specific stimulus detection. The review examines how HA-PEG-PCL system structures link to their properties and performance from copolymer production through physicochemical features and self-assembly behavior to therapeutic performance assessment. HA-PEG-PCL copolymers form micellar nanoparticles which range from 50 to 200 nanometers in size and maintain stability during systemic circulation through their low critical micelle concentrations which range from 10⁻⁵ to 10⁻⁷ M. The experimental studies demonstrate that the drug loading efficiencies reach between 70 and 90% which surpasses the efficiency of most traditional polymeric carriers. The presence of hyaluronic acid enables CD44 active targeting which results in CD44-overexpressing cancer cells absorbing 2 to 4 times more than non-targeted systems. The in vivo studies show that tumor accumulation increases approximately three times while enhancing therapeutic efficacy when compared to free medicines. The HA-PEG-PCL nanocarriers show 2 to 5 times lower IC₅₀ values for doxorubicin and paclitaxel which demonstrates their improved ability to transport drugs into cells and kill cancer cells. The copolymer structure permits multiple stimuli detection at pH levels below 7 and redox reactions and high temperatures which enables controlled drug release in tumor microenvironments. The preclinical results show promise but the research faces challenges because the technology needs to develop methods for scalable synthesis and catalyst-free production and regulatory approval processes. The HA-PEG-PCL triblock copolymers function as a flexible platform which scientists can adapt to create new targeted nanomedicine and multimodal cancer treatments.

Graphical Abstract

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透明质酸-聚（乙二醇）-聚（ε-己内酯）（HA-PEG-PCL）两亲三嵌段共聚物的刺激响应自组装和胶体性质

透明质酸-聚（乙二醇）-聚（ε-己内酯）（HA-PEG-PCL）两亲性三嵌段共聚物作为多功能纳米载体，通过其主动靶向能力和延长血液存在时间以及在特定刺激检测时释放药物的能力来提供癌症治疗。本文综述了HA-PEG-PCL体系结构如何从共聚物生产、物理化学特征和自组装行为到治疗性能评估等方面与它们的性能和性能联系起来。HA-PEG-PCL共聚物形成胶束纳米粒子，其大小从50到200纳米不等，并通过其低临界胶束浓度（范围从10⁻- 5到10⁻⁷m）在体循环中保持稳定性。实验研究表明，药物装载效率达到70%至90%，超过了大多数传统聚合物载体的效率。透明质酸的存在使CD44活性靶向，导致CD44过表达的癌细胞吸收比非靶向系统多2至4倍。体内研究表明，与免费药物相比，肿瘤积累增加了约三倍，同时提高了治疗效果。HA-PEG-PCL纳米载体显示阿霉素和紫杉醇的IC₅0值降低2至5倍，这表明它们提高了将药物转运到细胞中并杀死癌细胞的能力。共聚物结构允许在pH值低于7、氧化还原反应和高温下检测多种刺激，从而在肿瘤微环境中控制药物释放。临床前的结果显示出了希望，但这项研究面临着挑战，因为该技术需要开发可扩展的合成方法、无催化剂生产和监管审批流程。HA-PEG-PCL三嵌段共聚物作为一个灵活的平台，科学家可以适应它来创造新的靶向纳米药物和多模式癌症治疗。图形抽象

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来源期刊

Colloid and Polymer Science 化学-高分子科学

CiteScore

4.60

自引率

4.20%

发文量

111

审稿时长

2.2 months

期刊介绍： Colloid and Polymer Science - a leading international journal of longstanding tradition - is devoted to colloid and polymer science and its interdisciplinary interactions. As such, it responds to a demand which has lost none of its actuality as revealed in the trends of contemporary materials science.