Water-dispersible multifunctional hybrid nanogels for combined curcumin and photothermal therapy.

We design a class of water-dispersible hybrid nanogels for intracellular delivery of hydrophobic curcumin. The core-shell structured hybrid nanogels were synthesized by coating the Ag/Au bimetallic nanoparticles (NPs) with a hydrophobic polystyrene (PS) gel layer as inner shell, and a subsequent thin hydrophilic nonlinear poly(ethylene glycol) (PEG)-based gel layer as outer shell. The uniqueness of these hybrid nanogels lies in the integration of the functional building blocks for combined curcumin and photothermal therapy to significantly improve the therapeutic efficacy. The Ag/Au core NPs cannot only emit strong fluorescence for imaging and monitoring at the cellular level, but also exhibit strong absorption in the near-infrared (NIR) region for photothermal conversion. While the inner PS gel layer is introduced to provide strong hydrophobic interactions with curcumin for high drug loading yields, the external nontoxic and thermo-responsive PEG analog gel layer is designed to trigger the release of the pre-loaded curcumin either by variation of surrounding temperature or exogenous irradiation with NIR light. Such designed multifunctional hybrid nanogels are well suited for in vivo studies and clinical trials, thereby likely to bring this promising natural medicine of curcumin to the forefront of therapeutic agents for cancers and other diseases.