Proton-Driven Deformability Enables Nanozyme-Integrated Vaccine for Enhanced Tumor Immunotherapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Immunology

Background:

• Cancer immunotherapy using vaccines shows promise for tumor regression and metastasis prevention.
• Designing effective cancer vaccines is challenging due to difficulties in lymph node (LN) targeting, dendritic cell (DC) uptake, and cellular immunity activation.

Purpose of the Study:

• To develop a proton-driven, multifunctional nanovaccine (PP@Pt-OVA) that overcomes limitations in current cancer vaccine design.
• To enhance LN targeting, DC uptake, and cellular immunity activation for improved cancer immunotherapy.

Main Methods:

• A nanovaccine (PP@Pt-OVA) was engineered using PVP@Pt nanozymes and OVA peptides within PEG-b-PAE micelles.
• The nanovaccine utilizes proton-driven morphology changes in acidic LN environments to optimize LN retention and DC uptake.
• Nanozyme catalysis generates reactive oxygen species (ROS) to promote endosomal escape, antigen cross-presentation, and DC maturation.

Main Results:

• PP@Pt-OVA demonstrated efficient LN targeting and enhanced DC uptake.
• The nanovaccine successfully activated CD8+ T cells and inhibited tumor growth in prophylactic and therapeutic melanoma models.
• PP@Pt-OVA exhibited excellent biocompatibility and minimal systemic toxicity.

Conclusions:

• PP@Pt-OVA serves as a versatile nanovaccine platform with potential for advancing cancer immunotherapy.
• The rational design framework addresses limitations of subunit vaccines, offering a promising strategy for cancer treatment.