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) (mPEG) 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-mPEG-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.

Abstract from PubMed Central (PMID 42947100, PMC13715119). This entry was added automatically by our daily literature monitor because it matches the topics we follow; read the full paper at the original source.