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

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cancer Therapy

Background:

• The tumor microenvironment presents significant challenges for effective cancer treatment.
• Developing efficient multimodal nanomaterials is crucial for advancing tumor therapy.

Purpose of the Study:

• To introduce a novel nanomaterial, Cu-Cy Nps@ZIF-8@HA (CNZH), for the treatment of cutaneous squamous cell carcinoma (cSCC).
• To evaluate the synthesis, biocompatibility, tumor-targeting specificity, and therapeutic efficacy of CNZH.

Main Methods:

• Cu-Cy Nanoparticles (Cu-Cy Nps) were synthesized and encapsulated within zeolitic imidazolate framework-8 (ZIF-8), then surface-modified with hyaluronic acid (HA) to form CNZH.
• In vitro studies included hemolysis assays, CCK-8 cytotoxicity tests, cellular uptake (TEM), and reactive oxygen species (ROS) generation assays.
• In vivo studies utilized an A-431 xenograft mouse model, followed by TUNEL apoptosis assay, ROS staining, and immunohistochemical examination.

Main Results:

• CNZH demonstrated excellent biocompatibility and efficient cellular uptake by A-431 cells.
• The nanomaterial exhibited significant ROS generation, GSH depletion, and singlet oxygen (¹O₂) production.
• In vivo, CNZH significantly reduced tumor volume in the A-431 xenograft model, showing synergistic anti-cancer effects through combined chemotherapy and photodynamic therapy (CDT/PDT).

Conclusions:

• CNZH is a novel ZIF-8-based nanomaterial with intrinsic enzymatic activities and ¹O₂ generation capabilities.
• CNZH effectively targets tumor cells and exhibits potent synergistic anti-cancer effects via CDT/PDT, while maintaining excellent biosafety.
• CNZH represents a promising nanomaterial for synergistic treatment of cSCC, opening new therapeutic avenues.