Physical or chemical crosslinking of polymeric micelles has emerged as a straightforward approach to overcome the intrinsic instability of assemblies. However, the crosslinking process may compromise the responsivity of nanosystems and result in inefficient release of payloads. To address this dilemma, a crosslinking induced reassembly (CIRA) strategy is reported here to simultaneously increase the kinetic and thermodynamic stability and redox-responsivity of polymeric micelles. It is found that the click crosslinking of a model multiblock polyurethane at the micellar interface induces microphase separation between the soft and hard segments. The aggregation of hard domains gathers liable disulfide linkages around the interlayer of micelles, which could facilitate the attack of reducing agents and act as an intelligent on-off switch for high stability and triggered release. As a result, the CIRA approach enables an enhanced tumor targeting, improved biodistribution and excellent therapeutic efficacy in vivo. This work provides a facile and versatile platform for controlled delivery applications.

中文翻译：

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交联诱导多嵌段聚合物的重组：解决稳定性和响应性的困境。

聚合物胶束的物理或化学交联已成为克服组件固有不稳定性的直接方法。然而，交联过程可能会损害纳米系统的响应性并导致有效负载释放效率低下。为了解决这一困境，本文报道了一种交联诱导重组（CIRA）策略，以同时提高聚合物胶束的动力学和热力学稳定性以及氧化还原响应性。研究发现，模型多嵌段聚氨酯在胶束界面处的点击交联会引起软链段和硬链段之间的微相分离。硬域的聚集在胶束层间聚集了可靠的二硫键，这可以促进还原剂的攻击，并充当智能开关，实现高稳定性和触发释放。因此，CIRA 方法能够增强肿瘤靶向性、改善生物分布并实现出色的体内治疗效果。这项工作为受控交付应用程序提供了一个简便且多功能的平台。