Facile preparation of hyperbranched polymers (HPs) has been advanced tremendously by the use of either various multifunctional agent-mediated controlled living radical polymerizations or a highly reactive AB_x unit-modulated self-stepwise polymerizations. However, it remains, to our knowledge, a significant challenge to prepare HPs with simultaneously precisely controlled degree of branching (DB) and biorelevant signal-triggered degradation property for controlled release applications due to the respective limitations of the aforementioned two strategies. For this purpose, a triple functional AB₂ unit, A-SS-B₂ chain transfer agent (AB₂ CTA), that integrates the merits of both multifunctional agents and highly reactive AB_x units was designed and synthesized successfully to include a disulfide bond for reduction-triggered polymer degradation toward promoted intracellular release of encapsulated cargoes, a trithiocarbonate group for a universal reversible addition-fragmentation chain transfer (RAFT) polymerization of any vinyl-based monomer, and three terminal groups consisting of one azide and two alkyne functions for the generation of hyperbranched topology via a self-click coupling-based polymerization. A subsequent self-click polymerization of the resulting AB₂ CTA by click coupling in the presence of CuSO₄·5H₂O and sodium ascorbate (NaVc) generated a hyperbranched polymer template (HPT) with precisely modulated DB and a plurality of CTA units for a universal reversible addition-fragmentation chain transfer (RAFT) polymerization of any vinyl-containing monomer. The HPT was next used as a multimacro-CTA for RAFT polymerization of a typical hydrophilic monomer, oligo(ethylene glycol) monomethyl ether methacrylate (OEGMA), to demonstrate the potential of this HPT for a robust and facile production of bioreducible hyperbranched polymers for controlled release applications. The synthesized HPT-4-POEGMA can form unimolecular micelles with enhanced stability due to the hyperbranched structure, and the size of micelles varied in the range from 82.4 to 140.3 nm by a modulation of the molar feed ratio of monomer to HPT and polymerization time. More importantly, HPT-POEGMA micelles incubated with 10 mM glutathione (GSH) showed reduction-triggered cleavage of the disulfide links and polymer degradation for promoted intracellular doxorubicin (DOX) release and enhanced therapeutic efficiency. Taken together, this triple functional AB₂ CTA provided a powerful means for the facile preparation of bioreducible hyperbranched polymers with precisely controlled DB for controlled release applications.

中文翻译：

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可生物还原的超支化共聚物的三官能AB ₂单元调节的简便制备方法

通过使用多种多功能剂介导的受控活性自由基聚合反应或高反应性AB _x单元调节的自逐步聚合反应，超支化聚合物（HPs）的简便制备已得到了极大的发展。然而，据我们所知，由于上述两种策略各自的局限性，制备具有同时精确控制的支化度（DB）和生物相关信号触发降解性能的控释应用的HP仍然是一项重大挑战。为此目的，三元功能AB ₂单元A-SS-B ₂链转移剂（AB ₂ CTA）融合了多功能剂和高反应性AB _x的优点设计并成功合成了两个单元，包括一个二硫键，用于还原触发的聚合物降解，以促进封装货物的胞内释放；一个三硫代碳酸酯基团，用于任何乙烯基类单体的通用可逆加成-断裂链转移（RAFT）聚合；以及三个端基由一个叠氮化物和两个炔烃官能团组成，可通过基于自点击偶联的聚合反应生成超支化拓扑。在CuSO ₄ ·5H ₂的存在下，通过点击偶联，对所得的AB ₂ CTA进行随后的点击聚合。O和抗坏血酸钠（NaVc）生成了具有精确调节的DB和多个CTA单元的超支化聚合物模板（HPT），用于任何含乙烯基单体的通用可逆加成-断裂链转移（RAFT）聚合。接下来，该HPT用作多CTA，用于RAFT聚合典型的亲水单体，低聚（乙二醇）单甲基醚甲基丙烯酸甲酯（OEGMA），以证明该HPT在稳健而又容易地生产可生物还原的高支化聚合物用于受控方面的潜力发布应用程序。合成的HPT-4-POEGMA由于具有超支链结构而可以形成具有增强稳定性的单分子胶束，并且通过调节单体与HPT的摩尔进料比和聚合时间，胶束的尺寸在82.4至140.3 nm的范围内变化。更重要的是，与10 mM谷胱甘肽（GSH）孵育的HPT-POEGMA胶束显示出还原触发的二硫键裂解和聚合物降解，从而促进了细胞内阿霉素（DOX）的释放并提高了治疗效率。结合起来，这三功能AB₂ CTA提供了一种功能强大的方法，可轻松制备具有可控释放应用的精确控制DB的生物可还原超支化聚合物。