The preparation of various types of miktoarm star polymers with precisely controlled structures (A₂B, ABC, AB₂C₂, etc.) has made significant progress due to the considerable advances in the synthetic strategies, including multistep protections/deprotections, orthogonality, and integration of different polymerization techniques. However, compared to the well-developed synthesis methodologies, the investigations on miktoarm star copolymers as drug delivery vehicles remain relatively unexplored, especially for the relationship of their branched structures and properties as drug delivery systems. To elucidate this structure–property relationship of amphiphilic miktoarm star polymers, we prepared four different amphiphilic miktoarm star copolymers with the respectively identical molecular weights (MWs) of hydrophilic and hydrophobic moieties but different star structures using heteroinitiators that were synthesized by protection/deprotection strategies for integrated ring-opening polymerization of hydrophobic ε-caprolactone and atom transfer radical polymerization of hydrophilic oligo (ethylene glycol) monomethyl ether methacrylate (OEGMA). Further screening of an optimal formulation for anticancer drug delivery by the stability of micelles, in vitro drug loading capacity, drug release properties, cellular uptake efficacy, and cytotoxicity of doxorubicin (DOX)-loaded micelles showed that PCL₃POEGMA₁ micelles possessed the lowest critical micelle concentration, the highest drug loading content, and enhanced therapeutic efficiency for DOX release of all the synthesized four star copolymer constructs. This study thus provides preliminary guidelines and rationalities for the construction of amphiphilic miktoarm star polymers toward enhanced anticancer drug delivery.

中文翻译：

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两亲性Miktoarm星型共聚物的抗癌药物传递优化

制备具有精确控制结构的各种类型的米克星型聚合物（A ₂ B，ABC，AB ₂ C ₂等）在合成策略方面取得了长足的进步，包括多步保护/脱保护，正交性以及各种聚合技术的整合。但是，与发达的合成方法相比，关于作为药物传递载体的米克臂星型共聚物的研究仍相对较少，特别是对于它们的支链结构与作为药物传递系统的性质之间的关系。为了阐明两亲性米克星型星形聚合物的这种结构与性质的关系，我们制备了四种不同的两亲米克星型星形共聚物，其亲水和疏水部分的分子量（MWs）分别相同，但使用通过保护/脱保护策略合成的疏水性ε-己内酯的开环聚合和原子转移策略合成的杂化引发剂亲水性低聚（乙二醇）单甲基醚甲基丙烯酸酯（OEGMA）的自由基聚合。通过胶束的稳定性，体外载药量，药物释放特性，细胞吸收功效和载有阿霉素（DOX）的胶束的细胞毒性进一步筛选抗癌药物递送的最佳制剂，结果表明PCL₃ POEGMA ₁胶束具有最低的临界胶束浓度，最高的载药量，并且在所有合成的四星共聚物构建体中提高了DOX释放的治疗效率。因此，本研究为构建两亲性米克星型多聚体以增强抗癌药物的传递提供了初步的指导原则和合理性。