Partitioned Microneedle\nPatch Based on NO Release\nand HSP Inhibition for mPTT/GT Combination Treatment of Melanoma

Photothermal therapy (PTT) shows promise in cancer treatments\ndue\nto its good spatiotemporal selectivity and minimal invasiveness. However,\nPTT has some problems such as excessive heat damage to normal tissues,\ntumor thermo-resistance caused by heat shock proteins (HSPs), and\nlimited efficacy of monotherapy. Here, we construct a patch named\n“partitioned microneedles” (PMN-SNAP/CuS), which separates\nthe “catalyst” bovine serum albumin-based copper sulfide\nnanoparticles (CuS@BSA NPs) and the “reactant” <i>S</i>-nitroso-<i>N</i>-acetylpenicillamine (SNAP)\ninto different regions of microneedles, for enhancing mild PTT (mPTT)\nof melanoma. PMN-SNAP/CuS showed an excellent photothermal effect,\nFenton-like catalytic activity, and nitric oxide (NO) generation ability.\nThe combination of NO and reactive oxygen species (ROS) produced by\nPMN-SNAP/CuS effectively blocked the synthesis of HSPs at the source\nand enhanced the efficacy of mPTT. Both in vitro and in vivo results\nproved that PMN-SNAP/CuS significantly enhanced the inhibition of\nmelanoma under 808 nm laser irradiation. In conclusion, our partitioned\nmicroneedle strategy based on the combination of enhanced mPTT and\ngas therapy (GT) provides a promising approach to enhance the therapeutic\neffect on melanoma.