Membrane-Coated Iron Oxide (Fe3O4) Nanoparticles Encapsulating Dacarbazine Suppress B16F10 Melanoma Cell Activity in vitro and in a Subcutaneous Mouse Model

Hao Ding, Dan li Li, Zi yi Zhou, Xiang Dong Lai, Nan Yang, Liu chang Tan, Yuan gang LuDepartment of Plastic & Cosmetic Surgery, Daping Hospital Army Medical University, Chongqing, 400042, People’s Republic of ChinaCorrespondence: Yuan gang Lu, Department of Plastic & Cosmetic Surgery, Daping Hospital Army Medical University, Chongqing, 400042, People’s Republic of China, Email skin515@tmmu.edu.cnBackground: Malignant melanoma is a highly aggressive skin cancer. Dacarbazine (DTIC) chemotherapy, while historically used, is limited by poor solubility, short half-life, and systemic toxicity. Fe3O4 nanoparticles have been explored as drug delivery vectors with potential for photothermal conversion and Fenton-like catalytic activity. Cell membrane-camouflaged platforms may offer improved tumor targeting.Methods: A biomimetic nanoplatform (Fe3O4PD@CCM) was engineered by encapsulating an Fe3O4 core within a DTIC-loaded PLGA-PEG2000 matrix, followed by functionalization with B16F10 cancer cell membranes. Physicochemical properties were characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM), and liquid chromatography–mass spectrometry (LC-MS). Antitumor effects were assessed in B16F10 melanoma cells and in a subcutaneous syngeneic mouse model (n=4 per group).Results: Fe3O4PD@CCM Nanoparticles (NPs) exhibited a hydrodynamic diameter of ~25– 30 nm, sustained DTIC release, and retention of membrane proteins. In vitro, the Fe3O4PD@CCM + NIR (Near-infrared irradiation) group showed reduced cell viability, increased apoptosis, G2/M phase arrest, and elevated intracellular reactive oxygen species (ROS) levels compared to controls. In vivo, Cy5-labeled Fe3O4PD@CCM NPs showed preferential fluorescence accumulation in tumors relative to non-coated NPs, with whole-body fluorescence diminishing within 24 h. In a 12-day efficacy study, Fe3O4PD@CCM + NIR treatment was associated with reduced tumor growth compared to control groups. Acute biosafety assessment at 24 h post-injection of a single high dose (200 mg/kg) revealed no overt abnormalities in the evaluated hematological, biochemical, or histopathological parameters.Conclusion: Fe3O4PD@CCM NPs combined with NIR suppressed B16F10 cell activity in vitro and subcutaneous tumor growth in a preliminary mouse model. These findings represent a proof-of-concept demonstration. Further studies—including detailed mechanistic validation, long-term toxicity assessment, and evaluation in more clinically relevant models—are required to assess the translational potential of this platform.Keywords: malignant melanoma, dacarbazine, iron oxide nanoparticles, near-infrared irradiation