Lipid Membrane-Wrapped Zeolitic Imidazolate Framework-8 for Synergistic Chemotherapy and Photothermal Therapy to Target Prostate Cancer

Abstract

Endocrine therapy is often used for advanced prostate cancer. However, with cancer progress, prostate cancer gradually resistant to hormone which lead to serious threatens to life of patients. Herein, a multifunctional synergistic core–shell nanoplatform is reported for improving the therapeutic effect of chemotherapy for advanced or metastatic prostate cancer, and reducing the risk of leakage of chemotherapy drugs. Particularly, Zeolitic imidazolate framework-8 (ZIF-8) is chosen as inner core to load doxorubicin, and the of liposomes which are embedded with IR780 iodide are used as outer shell, and further modified with target ligand that binds to luteinizing hormone releasing hormone receptor. The prepared nanocarrier exhibit satisfactory photothermal effect under near infrared laser irradiation, and the temperature increases to 60.8 °C within 6 min. Meanwhile, the elevated temperature accelerates the degradation of lipid shell, releasing ZIF-8 core to acidic microenvironment of tumor, and resulting in the release of doxorubicin. Moreover, in vivo and in vitro studies have shown the ZIF-D@ALIP core–shell nanoparticles can achieve targeted drug delivery, pH and NIR dual stimuli-responsive drug release, as well as chemotherapy and photothermal therapy synergistically on the tumor site. In addition, the problem of premature leakage and changes in the physicochemical properties of anticancer drugs are avoided under the protection of the outer shell structure. Therefore, the core–shell nanostructure proposes a new lipid membrane coating strategy to promote the effective targeting of prostate cancer cells or tissues and provides some insights in clinical treatment for advanced prostate cancer.