Manganese dioxide-entrapping dendrimers as a therapeutic peptide vaccine for combined tumor chemodynamic/immune therapy and tumor prevention

Developing a vaccine that can both elicit robust antitumor immune responses and exert potent tumoricidal effects remains a formidable challenge. Herein, we design a functional dendrimer nanocarrier to co-deliver manganese dioxide (MnO 2 ) nanoparticles (NPs) and ovalbumin peptide antigen OVA 257−264 for synergistic tumor chemodynamic/immunotherapy and tumor prevention. Specifically, generation 5 (G5) poly(amidoamine) dendrimers functionalized with methoxy poly(ethylene glycol) ( m PEG) and heptafluorobutyric acid (HFBA) were used to entrap MnO 2 NPs with an average size of 2.6 nm and complex OVA 257−264 . The ultimately constructed MnO 2 @G5- m PEG-HFBA/OVA 257−264 (MGPF/OVA 257−264 ) NPs respond to tumor microenvironment for rapid release of Mn 2+ that can catalyze a Fenton-like reaction to initiate chemodynamic therapy (CDT) for tumor cell immunogenic cell death (ICD) induction and promote tumor-associated macrophage M1 polarization. The generated ICD combined with Mn²⁺-mediated stimulator of interferon genes (STING) pathway activation can synergize the co-delivered OVA 257−264 antigen to facilitate maturation of dendritic cells for cross-presentation of antigens. In a mouse subcutaneous colorectal cancer model, the MGPF/OVA 257−264 nanovaccine exhibits potent therapeutic and prophylactic efficacy, markedly suppressing tumor growth and recurrence through CDT cytocidal effect and robust immune activation. The developed dendrimer-based theranostic peptide nanovaccine may be extended to tackle other types of solid tumors through cooperatively potentiating antitumor immune responses.