Abstract
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.
Highlights
Physical or chemical crosslinking of polymeric micelles has emerged as a assemblies cannot withstand the massive dilution and competing interactions with straightforward approach to overcome the intrinsic instability of assemblies
The crosslinking process may compromise the responsivity of nature and intrinsic instability, leading to nanosystems and result in inefficient release of payloads
We found that the diameters and size distributions of multiblock polyurethane (MPU) micelles increased greatly with water or buffer addition, while those of crosslinked MPU micelles (CMPU) were almost unchanged even when diluted more than 700 times (Figure 1A–C and Figures S15 and S16, Supporting Information)
Summary
Fluorescent imaging of the anatomized organs of the mouse sacrificed at 24 h evidenced an improved biodistribution of DOX for CMPU formulation, where the fluorescence in tumor was greatly enhanced while those in liver, spleen, and kidney were significantly minimized (Figure 3F and Figure S28, Supporting Information).
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