Cu-Cy Nps@ZIF-8@HA-Mediated Photodynamic Therapy for Cutaneous Squamous Cell Carcinoma

The complex tumor microenvironment poses an important challenge for the effective treatment of tumors, so it is important to develop efficient multimodal nanomaterials for tumor therapy. This study introduces a novel nanomaterial, Cu-Cy Nps@ZIF-8@HA (CNZH), based on zeolitic imidazolate framework-8 (ZIF-8) backbone. CNZH offers the combined merits of facile synthesis, environmental benignity, and effective therapeutic performance against cutaneous squamous cell carcinoma(cSCC).

The photosensitizer Cu-cy Nps (Cu-Cy Nanoparticles) was initially synthesized and subsequently encapsulated within a zeolitic imidazolate framework-8 framework to construct Cu-cy Nps@ZIF-8 (CNZ), which was further surface-modified with hyaluronic acid(HA) to yield the final nanocomposite CNZH. In vitro evaluations demonstrated excellent biocompatibility, as evidenced by hemolysis assays and CCK-8 cytotoxicity tests. Transmission electron microscopy (TEM) confirmed efficient cellular uptake by A-431 cells, while Western blot analysis validated its tumor-targeting specificity. Functional characterization revealed CNZH's remarkable capacity for reactive oxygen species(ROS) generation, GSH depletion, and singlet oxygen (¹O₂) production. For in vivo assessment, an A-431 xenograft mouse model was established, with subsequent tumor tissue analyses including TUNEL apoptosis assay, ROS staining, and immunohistochemical examination, collectively demonstrating the nanocomposite's significant therapeutic efficacy and precise tumor-targeting capability.

This study successfully designed and fabricated a novel ZIF-8-based nanomaterial, CNZH, which exhibits POD, CAT, and GSH-Px enzymatic activities along with the capability to generate ¹O₂. In vitro, the apoptosis rate of A-431 cells treated with LCNZH (CNZH+UV) was 77.1% (predominantly early apoptosis),the survival rate of A-431 cells treated with 200 μg/mL CNZH for 24h was 32%, which was significantly lower than that of the CNZ group (65%, P<0.05). In vivo, the tumor volume of the LCNZH group was significantly smaller than that of the PBS and CNZ groups after 12 days of treatment. PBS control, no-light groups Both in vitro and in vivo experimental results demonstrated that CNZH can effectively target tumor cells, synergistically exert outstanding anti-cancer effects through combined CDT/PDT therapy, while maintaining excellent biosafety.

CNZH is expected to be a highly efficient nanomaterial for the synergistic treatment of cutaneous squamous cell carcinoma, thereby opening up a new avenue for the application of nanomaterials in the treatment of this malignancy.