Rapid synthesis of a Bi@ZIF-8 composite nanomaterial as a near-infrared-II (NIR-II) photothermal agent for the low-temperature photothermal therapy of hepatocellular carcinoma

Hepatocellular carcinoma is the fourth leading cause of cancer-related deaths globally. Advanced nanomaterials have emerged as effective approaches to liver cancer therapy such as photothermal therapy. However, limited penetration depth of photothermal agents (PTAs) activated in the NIR-I bio-window and thermoresistance due to heat shock proteins restrict the therapeutic efficacy of PTT in HCC. Herein, we prepared a Bi@ZIF-8 (BZ) nanomaterial by a simple one-step reduction method. Then, gambogic acid, a natural inhibitor of Hsp90, was efficiently loaded onto the BZ nanomaterialviaphysical mixing. The characterization of the nanomaterial and release of GA due to pH change or NIR-light irradiation were separately studied. Photothermal conversion efficiency was calculated, and therapeutic studies were carried outin vitroandin vivo. This nanomaterial exhibited a significantly enhanced drug release rate when the temperature was increased under acidic conditions and had good light stability under laser irradiation and a photothermal conversion efficiency of about 24.4%. In addition, this novel nanomaterial achieved good therapeutic effects with less toxicityin vitro.The BZ nanomaterial loaded with GA caused tumor shrinkage as well as disappearance and effectively downregulated Hsp90 expression in tumorsin vivo. Moreover, this novel nanomaterial exhibited good biocompatibility and potential for application in low-temperature PTT with excellent tumor destruction efficacy.