CuS Nanoparticles-Loaded and Cisplatin Prodrug Conjugated Fe(III)-MOFs for MRI-Guided Combination of Chemotherapy and NIR-II Photothermal Therapy.

Ovarian cancer has become an urgent threat to global female healthcare. Cisplatin, as the traditional chemotherapeutic agent against ovarian cancer, retains several limitations, such as drug resistance and dose-limiting toxicity. In order to solve the above problems and promote the therapeutic effect of chemotherapy, combining chemotherapy and phototherapy has aroused wide interest. In this study, we constructed a versatile cisplatin prodrug-conjugated therapeutic platform based on ultrasmall CuS-modified Fe(III)-metal-organic frameworks (MIL-88) (named M-Pt/PEG-CuS) for tumor-specific enhanced synergistic chemo-/phototherapy. After intravenous injection, M-Pt/PEG-CuS presented obvious accumulation in tumor and Fe(III)-MOFs possessed magnetic resonance imaging (MRI) to guide synergy therapy. Both in vitro and in vivo experimental results showed that M-Pt/PEG-CuS could not only successfully inhibit tumor growth by combining chemotherapy and NIR-II PTT but also avoid the generation of liver damage by the direct treatment of cisplatin(II). Our work presented the development of the nanoplatform as a novel NIR-II photothermal agent, as well as gave a unique combined chemo-photothermal therapy strategy, which might provide new ways of ovarian cancer therapy for clinical translation.

A Cu9S5 nanoparticle-based CpG delivery system for synergistic photothermal-, photodynamic- and immunotherapy.

Despite its great potential in cancer therapy, phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT), often cause metastasis of tumors. Immunotherapy has revolutionized the cancer treatment owing to the capability of activating immune system to eliminate tumors. However, the integration of phototherapy and immunotherapy in a single nanoagent for cancer therapy is still a challenging task. Here, we fabricated (Cu9S5@mSiO2-PpIX@MnO2@CpG (CSPM@CpG)) as a synergistic therapeutic model for phototherapy enhanced immunotherapy. The intracellular uptake of cytosine-phosphate-guanine (CpG) promoted the infiltration of cytotoxic T lymphocytes (CTLs) in tumor tissue, further stimulating the production of interferon gamma (IFN-γ) and remarkably elevating the immune response level. Excellent anti-tumor effects have been achieved by synergistic PTT/PDT/immunotherapy. The metastasis of tumors was effectively inhibited by the immune response of CpG. Thus, our proposed work provides a strategy to combine phototherapy with immunotherapy to enhance the therapeutic efficiency and further inhibit metastasis of tumors.