具有最小溶血活性的自组装多电解质药物偶联物用于精确肿瘤学

IF 6.3 2区化学 Q1 POLYMER SCIENCE

European Polymer Journal Pub Date : 2025-09-25 DOI:10.1016/j.eurpolymj.2025.114319

Dimitra Toumpa , Valentini Vasileiou , Athina Angelopoulou , Konstantinos Avgoustakis , George Pasparakis

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引用次数: 0

摘要

我们报道了一种定义明确、自组装的多电解质药物偶联物（PDCs）的合成，用于精确治疗具有最小溶血活性的胰腺癌。聚乙二醇嵌段共聚物（PEG）与阳离子聚（2-二甲氨基乙基甲基丙烯酸酯）（PDMAEMA）或阴离子hpma -琥珀酸酯（HPMA-Suc）与反离子聚甲基丙烯酸酯-吉西他滨（GEM）或喜树碱（CPT）的药物共聚物络合形成聚乙二醇屏蔽的聚电解质复合物（PECs）。所得到的纳米颗粒（40-220 nm）具有可调的表面电荷，高胶体稳定性，以及由连接剂化学和颗粒尺寸控制的释放曲线。针对PANC-1细胞的体外实验表明，几种PDCs和pecc -特别是cpt负载系统-达到的IC50值比免费药物低6个数量级。溶血试验证实了极好的生物相容性，在最高测试浓度下有5%的红细胞溶解。这些结果强调了一个多功能和安全的平台，用于开发基于聚电解质的纳米药物，具有强大的靶向癌症治疗潜力。

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Self-assembled polyelectrolyte drug conjugates with minimal hemolytic activity for precision oncology

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Self-assembled polyelectrolyte drug conjugates with minimal hemolytic activity for precision oncology

We report the synthesis of well-defined, self-assembled polyelectrolyte drug conjugates (PDCs) for precision pancreatic cancer therapy with minimal hemolytic activity. Block copolymers of poly(ethylene glycol) (PEG) with cationic poly(2-dimethylaminoethyl methacrylate) (PDMAEMA) or anionic HPMA-succinate (HPMA-Suc) were complexed with counterion polymethacrylate–drug copolymers of gemcitabine (GEM) or camptothecin (CPT) to form PEG-shielded polyelectrolyte complexes (PECs). The resulting nanoparticles (40–220 nm) displayed tunable surface charge, high colloidal stability, and controlled release profiles governed by linker chemistry and particle size. In vitro assays against PANC-1 cells showed that several PDCs and PECs—particularly CPT-loaded systems—achieved IC₅₀ values up to six orders of magnitude lower than the free drugs. Hemolysis assays confirmed excellent biocompatibility, with <5 % red blood cell lysis at the highest tested concentrations. These results highlight a versatile and safe platform for the development of polyelectrolyte-based nanomedicines with strong potential for targeted cancer therapy.

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来源期刊

European Polymer Journal 化学-高分子科学

CiteScore

9.90

自引率

10.00%

发文量

691

审稿时长

23 days

期刊介绍： European Polymer Journal is dedicated to publishing work on fundamental and applied polymer chemistry and macromolecular materials. The journal covers all aspects of polymer synthesis, including polymerization mechanisms and chemical functional transformations, with a focus on novel polymers and the relationships between molecular structure and polymer properties. In addition, we welcome submissions on bio-based or renewable polymers, stimuli-responsive systems and polymer bio-hybrids. European Polymer Journal also publishes research on the biomedical application of polymers, including drug delivery and regenerative medicine. The main scope is covered but not limited to the following core research areas: Polymer synthesis and functionalization • Novel synthetic routes for polymerization, functional modification, controlled/living polymerization and precision polymers. Stimuli-responsive polymers • Including shape memory and self-healing polymers. Supramolecular polymers and self-assembly • Molecular recognition and higher order polymer structures. Renewable and sustainable polymers • Bio-based, biodegradable and anti-microbial polymers and polymeric bio-nanocomposites. Polymers at interfaces and surfaces • Chemistry and engineering of surfaces with biological relevance, including patterning, antifouling polymers and polymers for membrane applications. Biomedical applications and nanomedicine • Polymers for regenerative medicine, drug delivery molecular release and gene therapy The scope of European Polymer Journal no longer includes Polymer Physics.