Multi‐Responsive Biodegradable Cationic Nanogels for Highly Efficient Treatment of Tumors

The facile preparation, modular design, and multi-responsiveness are extremely critical for developing pervasive nanoplatforms to meet heterogeneous applications. Here, cationic nanogels (NGs) are modularly engineered with tunable responsiveness, versatility, and biodegradation. Cationic PVCL-based NGs with core/shell structure are fabricated by facile one-step synthesis. The formed PVCL-NH2 NGs exhibit uniform size, thermal/pH dual-responsive behaviors, and redox-triggered degradation. Moreover, the NGs can be employed to modify or/and load with various functional agents to construct multipurpose nanoplatforms in a modular manner. Notably, the novel hybrid structure with copper sulfide (CuS) NPs loaded in the NGs shell is prepared, which leads to higher photothermal conversion efficiency (31.1%) than other CuS randomly loaded NGs reported. By personalized tailoring, these functionalized NGs display fluorescent property, r(1) relaxivity, strong near-infrared (NIR) absorption, good biocompatibility, and targeting specificity. The superior photothermal effect of hybrid NGs (CuS@NGs-LA) is presented under NIR II over NIR I. Importantly, hybrid NGs encapsulated doxorubicin (CuS@NGs-LA/DOX) show endogenous pH/redox and exogenous NIR multi-triggered drug release for efficient photothermal-chemotherapy, which can completely eliminate advanced tumors and effectively inhibit recurrence. Overall, the pervasive nanoplatforms based on intelligent cationic NGs with tunable responsiveness, versatility, and biodegradation are developed by engineered modular strategy for precision medicine applications.