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

Abstract

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 (Lornidamine@HMPB-Zn) with high photothermal conversion efficacy for dual glycolysis regulation and photothermal therapy. Lornidamine@HMPB-Zn 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.