Conjugation of small molecule drug to lipid‐polymer amphiphiles is a powerful strategy to alter the pharmacokinetic profile of these molecules by promoting binding to albumin or other serum molecules. Incorporation of a responsive linker between the lipid anchor and the polymer chain can be of interest to avoid indefinite binding of the conjugates to hydrophobic pockets of serum proteins or phospholipid membranes when reaching a target cell or tissue. Here, the synthesis of pH‐sensitive lipid‐polymer conjugates by reversible addition‐fragmentation chain transfer (RAFT) polymerization using a RAFT chain transfer agent that is equipped with a pH‐sensitive ketal bond between a cholesterol moiety and the trithiocarbonate RAFT chain transfer group is reported. It is demonstrated that in native form these conjugates exhibit a high affinity to albumin and cell membranes but loose this ability in response to a mild acidic trigger in aqueous medium.

中文翻译：

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使用Ketal功能化的RAFT链转移剂设计可pH降解的聚合物脂质两亲物

小分子药物与脂质聚合物两亲物的结合是通过促进与白蛋白或其他血清分子的结合来改变这些分子的药代动力学特征的强大策略。在脂质锚和聚合物链之间掺入反应性接头可能是令人感兴趣的，以避免当到达靶细胞或组织时，缀合物无限期地结合到血清蛋白或磷脂膜的疏水口袋上。在这里，使用RAFT链转移剂通过可逆的加成-断裂链转移（RAFT）聚合合成pH敏感的脂质-聚合物共轭物，该RAFT链转移剂在胆固醇部分和三硫代碳酸酯的RAFT链转移基团之间配备了pH敏感的缩酮键被报道。