A biomimetic therapeutic nanovaccine based on dendrimer–drug conjugates coated with metal–phenolic networks for combination therapy of nasopharyngeal carcinoma: an <i>in vitro</i> investigation

Developing a minimally invasive and potent therapy for nasopharyngeal carcinoma is still challenging. In this study, we report a photothermal nanovaccine based on phenylboronic acid (PBA)-modified poly(amidoamine) dendrimers of generation 5 (G5) attached with indocyanine green (ICG) as a photothermal agent, toyocamycin (Toy) as an endoplasmic reticulum stress (ERS) drug, and Mn²⁺-coordinated metal-phenolic networks. The developed nanocomplexes are camouflaged with homologous apoptotic cancer cell membranes, leveraging membrane proteins as an antigenic reservoir and incorporating the immune adjuvant cytosine-guanine (CpG) oligonucleotide to obtain the final nanovaccine formulation. The prepared nanovaccine with a size of 72.4 nm displays satisfactory colloidal stability and photothermal conversion efficiency (36.7%), and is capable of targeting cancer cells and inducing apoptosis under laser irradiation through combined ICG-mediated photothermal therapy, Toy-enabled chemotherapy and Mn²⁺-mediated chemodynamic therapy. Meanwhile, the combined therapeutic effects can elicit immune responses to mature dendritic cells through the immunogenic cell death of cancer cells and the inserted CpG adjuvant/apoptotic cancer cell membranes, and polarize tumor-associated macrophage cells to the antitumor M1 phenotype. The antitumor efficacy of the nanomedicine platform was proven by the test of the penetration and therapeutic inhibition of 3-dimensional tumor spheroids <i>in vitro</i>. The developed functional nanomedicine integrated with different therapeutic modes may be developed as a biomimetic therapeutic nanovaccine for nasopharyngeal carcinoma treatment.