Institute of Macromolecular Chemistry, Czech Academy of Sciences, Prague, Czech Republic.
Institute of Macromolecular Chemistry, Czech Academy of Sciences, Prague, Czech Republic.
J Control Release. 2020 Sep 10;325:304-322. doi: 10.1016/j.jconrel.2020.06.040. Epub 2020 Jul 9.
In the past decades, nanosized drug delivery systems based on N-(2-hydroxypropyl)methacrylamide copolymers (pHPMA) have gained increasing attention in nanomedicine field due to their hydrophilicity, versatility, biocompatibility, non-toxicity, and non-immunogenicity. Indeed, pHPMA nanosystems with various controlled drug release capabilities inside targeted tissues or cells have been intensively studied. This paper summarizes recent advances in the design and application of pHPMA conjugates with specific antibodies or their fragments, focusing predominantly on the systems for the cancer therapy, particularly, the mechanisms of action of therapeutic antibodies, the approaches of their modification and subsequent attachment of pHPMA and their conjugates with diverse active moieties. Finally, we highlight the major biomedical applications of these antibody-polymer-drug conjugates and consider directions of possible development over the coming decade.
在过去的几十年中,基于 N-(2-羟丙基)甲基丙烯酰胺共聚物 (pHPMA) 的纳米药物递送系统在纳米医学领域受到了越来越多的关注,因为它们具有亲水性、多功能性、生物相容性、无毒性和非免疫原性。事实上,具有各种控制药物释放能力的 pHPMA 纳米系统已经在靶向组织或细胞内得到了深入研究。本文总结了 pHPMA 缀合物与特定抗体或其片段的设计和应用的最新进展,主要集中在癌症治疗的系统上,特别是治疗性抗体的作用机制、修饰方法及其随后与 pHPMA 及其与各种活性部分的缀合物的连接。最后,我们强调了这些抗体-聚合物-药物缀合物的主要生物医学应用,并考虑了未来十年可能的发展方向。
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