Biomimetic Cancer Cell Membrane-Coated Polymeric Nanogels as a Therapeutic Vaccine for Synergistic Photothermo-Chemo-Immunotherapy of Nasopharyngeal Carcinoma.

Abstract

Nasopharyngeal carcinoma (NPC) therapy faces challenges including severe off-target toxicity and immunosuppression. Here, a biomimetic nanogel vaccine is developed based on dual pH/reactive oxygen species (ROS)-responsive poly(N-vinylcaprolactam) (PVCL) nanogels (NGs) that were co-loaded with indocyanine green (ICG) and the endoplasmic reticulum stress-inducing drug toyocamycin, followed by coating with cancer cell membranes (CMs) or exosomes (Exos). Systematic comparison reveals that CM coating confers better homologous targeting, cellular uptake, and immunogenicity than the Exo coating. The optimized IT@PVCL-CM NGs enable tumor microenvironment-triggered drug release, combined chemotherapy and mild photothermal therapy, and synergistic induction of immunogenic cell death (ICD). In an NPC mouse model, the IT@PVCL-CM combined with laser irradiation significantly promotes dendritic cell maturation through the combination therapy-mediated ICD effect and the CM antigens, CD8+ T cell infiltration, and long-term memory T cell responses, effectively suppressing both primary and distant tumors via an abscopal effect. Additionally, ICG endows dual-modal fluorescence and thermal imaging for real-time tumor monitoring. This work presents the integration of dual-responsive PVCL nanogels, dual ICD induction strategies through combination of photothermo-chemotherapy, and biomimetic membrane cloaking for precision NPC theranostics and immune activation.