基于可降解两性离子聚碳酸酯纳米胶束的设计合成及其血液长循环研究
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1.东部战区总医院;2.中国药科大学工学院

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Study on long blood-circulation of nano-micelles based on biodegradable zwitterionic polycarbonate
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    摘要:

    目的:纳米药物是肿瘤治疗的有效方式,但传统的纳米药物系统存在稳定性差、血液循环时间短和免疫原性等问题,因此拥有良好稳定性和非特异性蛋白质抗性的纳米载体在药物递送过程中具有重要意义。方法:为了克服传统纳米载体的局限性,本文通过开环聚合和Michael加成后聚合修饰设计并合成一种可生物降解的羧酸甜菜碱型两性离子功能化聚碳酸酯共聚物(PAC(TCB)),采用溶剂交换法制备得到尺寸为160 nm的胶束。结果:细胞摄取和毒性实验结果表明,PAC(TCB)胶束具有肿瘤细胞摄取效率高、生物相容性好的优点;溶血和体内血液循环实验结果显示,PAC(TCB)胶束具有低免疫原性和长循环特性,且多次注射后不会产生抗体效应。结论:综上,可生物降解的两性离子功能化聚碳酸酯作为纳米载体在体内药物递送领域具巨大潜力。

    Abstract:

    Objective: Nanomedicine is promising in conquering the tumor, while the traditional nano-vector is limited by poor stability, short blood circulation, and high immunogenicity. Hence, developing a novel nano-system with sterling stability and non-specific protein resistance for drug delivery is urgent. Methods:To overcome these challenges, we design a biodegradable carboxybetaine (CB)-modified polycarbonate (PAC(TCB)) synthesized by ring-opening polymerization and Michael addition reaction, which can form the micelles of around 160 nm via solvent displacement method. Results:We have demonstrated that the developed zwitterionic micelle possesses the superior characteristics of efficient cell internalization, excellent biocompatibility, low immunogenicity, and prolonged blood circulation. Moreover, our devised micelles will not produce antibody effects after repeated injections. Conclusion:Accordingly, the biodegradable carboxybetaine (CB)-modified polycarbonate displays colossal potential as the nano-vector in drug delivery.

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历史
  • 收稿日期:2023-08-08
  • 最后修改日期:2023-10-24
  • 录用日期:2024-02-27
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