Polydopamine-modified ZIF-8 nanoparticles as a drug carrier for combined chemo-photothermal osteosarcoma therapy

Single chemotherapy often causes severe adverse effects and chemoresistance which limits therapeutic efficacy. Recently, combination of chemotherapy with photothermal therapy (PTT) have received broad attention for synergistic treatment of osteosarcoma, ultimately resulting in the enhancement of therapeutic efficacy of anticancer drugs. In this study, we have developed a novel drug delivery system based on polydopamine (pDA)modified ZIF-8 nanoparticles loaded with methotrexate (MTX) (pDA/MTX@ZIF-8 NPs). Herein, pDA modification avoided the explosive release of the drug, and improved the biocompatibility and near-infrared (NIR) light absorbance performance of nanoparticles. The as-prepared pDA/MTX@ZIF-8 NPs could be used as drug targeting delivery system and simultaneously displayed excellent photothermal effects under NIR irradiation. Biology assays in vitro indicated that the pDA/MTX@ZIF-8 NPs were able to efficiently induce MG63 cell apoptosis through reducing mitochondrial membrane potentials (MMPs), and the introduction of photothermal agents enhanced the antitumor effect and decreased the dose of chemotherapeutic drugs. Moreover, the optimized pDA/ MTX@ZIF-8 NPs (40 mu g/mL) exhibited better photothermal conversion performance and facilitated tumor cells death. These results triumphantly exhibit that the pDA/MTX@ZIF-8 NPs have a synergistic effect of chemophotothermal therapy (combination index CI = 0.346) and excellent biocompatibility, which has unexceptionable prospects for the therapy of osteosarcoma.

Automated summary

This study develops a novel drug delivery system based on polydopamine-modified ZIF-8 nanoparticles loaded with methotrexate, and combines it with photothermal therapy, aiming to achieve synergistic treatment of osteosarcoma and enhance the therapeutic efficacy of anticancer drugs.