A multi-responsive Au NCs@PMLE/Ca antitumor hydrogel formed on the interior/surface of tumors for PT imaging-guided synergistic PTT/O-enhanced PDT effects.

At present, although phototherapy and related imaging have proven to be promising cancer diagnosis and treatment strategies, the free diffusion of photosensitizers into normal tissues can cause side effects, and the efficiency of photodynamic therapy (PDT) can also be limited by the tumor hypoxic microenvironment. Herein, we designed and prepared a new cancer nanoplatform containing Au nanoclusters (NCs)@ leaf extract (PMLE) with both responsiveness to near-infrared (NIR) laser irradiation and tumor microenvironment (TME) by facile redox and coordination reactions. Then, the Au NCs@PMLE/Ca hydrogel was constructed inside and on the surface of tumors for locoregional antitumor activity under 808 nm laser irradiation. The Au NCs@PMLE nanoplatform showed distinguished performance in killing cancer cells and alleviating tumor hypoxia by enhancing the temperature of the tumor sites and producing reactive oxygen species (ROS) under NIR irradiation as well as catalyzing hydrogen peroxide (HO) decomposition in TME for oxygen (O) generation catalase in PMLE. The ultra-small size of about 3 nm of the Au NCs in this nanoplatform was obtained using the biological molecules present in PMLE as reductants and coordination agents simultaneously, which also demonstrated the outstanding capability of photothermal (PT) imaging and photothermal therapy (PTT) towards tumors. Furthermore, the Au NCs@PMLE/Ca hydrogel formed through natural PMLE and intrinsic Ca in TME could not only improve the biocompatibility of the nanoplatform and stability of Au NCs but was also highly concentrated around the tumor thus enhancing the therapeutic efficiency and inhibiting its migration to normal tissues, decreasing the side effects. The results of the experiments confirmed that the Au NCs@PMLE/Ca hydrogel possessed PT imaging-guided NIR laser/TME-responsive synergetic cancer PTT/O-enhanced PDT and remarkable locoregional antitumor effect for cancer therapy. This work may open a new versatile route for multi-responsive localized cancer therapeutic nanoplatforms.