Zinc-enriched nanosystem for dual glycolysis regulation and photothermal therapy to synergistically inhibit primary melanoma and lung metastasis

Despite significant progress in melanoma treatment, low therapeutic efficacy frequently occurs in advanced-stage patients due to distant organ metastasis. We herein propose a zinc-enriched nanosystem ([email protected]) with high photothermal conversion efficacy for dual glycolysis regulation and photothermal therapy. [email protected] comprises zinc-bonded hollow mesoporous Prussian blue (HMPB-Zn) nanoparticles as a photothermal converter, dissociated zinc ions, and the loaded lonidamine as a glycolysis regulator. Upon near-infrared (NIR) laser irradiation, the heat energy generated by HMPB-Zn not only did induce cytotoxicity but also accelerated the dissociation of zinc ions and the release of LND, respectively inhibiting lactate dehydrogenase (LDHA) and hexokinase Ⅱ (HK2) to down-regulate the level of glycolysis. Additionally, the down-regulated expression of Akt, p-Akt, HIF-1α and cell cycle arrest induced by this nanosystem contributed to the potent antitumor efficacy in vitro and in vivo. Notably, the synergistic treatment nanosystem reduced the expression of metastasis-related proteins, inhibiting distant metastasis from subcutaneous melanoma to lung lesion. Thus, the present study provides a novel perspective for tumor metabolism and phototherapy to achieve complete tumor regression.