Multifunctional Chitosan/Porous Silicon@Au Nanocomposite Hydrogels for Long-Term and Repeatedly Localized Combinatorial Therapy of Cancer via a Single Injection.

Considering the future clinical applications of localized cancer therapy, it is of great importance to construct injectable biodegradable nanocomposite hydrogels with combinatorial therapeutic efficacy. Here, porous silicon nanoparticles (PSiNPs) as host matrix were chosen to fabricate PSiNPs@Au nanocomposites via in situ reductive synthesis of gold nanoparticles. Then PSiNPs@Au nanocomposites were further incorporated into thermosensitive chitosan (CS) hydrogels to construct CS/PSiNPs@Au nanocomposite hydrogels, which showed in situ gelation at physiological temperature, excellent biodegradability, and biocompatibility. Especially with the encapsulation of CS hydrogels, PSiNPs@Au nanocomposites had a long-term stable photothermal effect with higher local temperature under near-infrared (NIR) laser irradiation, whether in vitro or in vivo. Besides, assisted by NIR laser irradiation, CS/PSiNPs@Au nanocomposite hydrogels exhibited a long-term sustained release of anticancer drugs (doxorubicin hydrochloride, DOX) in acidic tumor environments. Finally, DOX/CS/PSiNPs@Au precursors were administrated into tumor-bearing mice via a single intratumoral injection, which presented a significant synergistic chemo-photothermal therapeutic efficacy under repeated NIR laser irradiation during long-term cancer treatments. Accordingly, we developed a novel strategy to prepare multifunctional CS/PSiNPs@Au nanocomposite hydrogels and also demonstrated their potential applications in localized cancer therapy in future clinics.