• The formation of manganese oxide induces self-assembly of block copolymers to form polymeric vesicles.

• The polymeric vesicles possessed strong stability and high drug loading capacity.

• The drug-loaded polymeric vesicles have been demonstrated, especially in in vivo studies, to exhibit a higher efficacy of tumor suppression without known cardiotoxicity.

Molecular self-assembly is crucially fundamental to nature. However, the aqueous self-assembly of polymers is still a challenge. To achieve self-assembly of block copolymers [(polyacrylic acid–block–polyethylene glycol–block–polyacrylic acid (PAA₆₈–b–PEG₈₆–b–PAA₆₈)] in an aqueous phase, manganese oxide (MnO₂) is first generated to drive phase separation of the PAA block to form the PAA₆₈–b–PEG₈₆–b–PAA₆₈/MnO₂ polymeric assembly that exhibits a stable structure in a physiological medium. The polymeric assembly exhibits vesicular morphology with a diameter of approximately 30 nm and high doxorubicin (DOX) loading capacity of approximately 94%. The transformation from MnO₂ to Mn²⁺ caused by endogenous glutathione (GSH) facilitates the disassembly of PAA₆₈–b–PEG₈₆–b–PAA₆₈/MnO₂ to enable its drug delivery at the tumor sites. The toxicity of DOX-loaded PAA₆₈–b–PEG₈₆–b–PAA₆₈/MnO₂ to tumor cells has been verified in vitro and in vivo. Notably, drug-loaded polymeric vesicles have been demonstrated, especially in in vivo studies, to overcome the cardiotoxicity of DOX. We expect this work to encourage the potential application of polymer self-assembly.

• 氧化锰的形成引起嵌段共聚物的自组装以形成聚合物囊泡。

• 聚合物囊泡具有很强的稳定性和高载药量。

• 已证明载药的聚合物囊泡，特别是在体内研究中，表现出更高的肿瘤抑制功效，而没有已知的心脏毒性。

分子自组装对于自然至关重要。然而，聚合物的水性自组装仍然是挑战。为了实现自组装嵌段共聚物的[（聚丙烯酸嵌段-聚乙二醇-框-polyacrylic酸（PAA ₆₈ - b -PEG ₈₆ - b -PAA ₆₈）]在水相中，氧化锰（MnO的₂）的第一生成以驱动PAA嵌段的相分离以形成PAA ₆₈ – b –PEG ₈₆ – b –PAA ₆₈ / MnO ₂在生理介质中显示稳定结构的聚合物组件。聚合物组件显示出直径约为30 nm的囊泡形态，阿霉素（DOX）的高负载能力约为94％。内源性谷胱甘肽（GSH）引起的从MnO ₂到Mn ²⁺的转化促进了PAA ₆₈ – b –PEG ₈₆ – b –PAA ₆₈ / MnO ₂的分解，使其能够在肿瘤部位递送。负载DOX的PAA ₆₈ – b –PEG ₈₆ – b –PAA ₆₈ / MnO ₂的毒性已经在体外和体内证实了对肿瘤细胞的杀伤作用。值得注意的是，已证明载有药物的聚合物囊泡克服了DOX的心脏毒性，尤其是在体内研究中。我们希望这项工作能够鼓励聚合物自组装的潜在应用。