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

Abstract

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 in vitro. The developed functional nanomedicine integrated with different therapeutic modes may be developed as a biomimetic therapeutic nanovaccine for nasopharyngeal carcinoma treatment.