Transdermal cold atmospheric plasma-mediated immune checkpoint blockade therapy

Area of Science:

• Oncology
• Immunology
• Biomedical Engineering

Background:

• Immune checkpoint blockade (ICB) therapy shows promise for cancer treatment but faces limitations like low response rates and systemic side effects.
• Current delivery methods for ICB can be invasive and lead to adverse reactions, necessitating innovative approaches.

Purpose of the Study:

• To develop and evaluate a novel transdermal drug delivery system integrating cold atmospheric plasma (CAP) with ICB for enhanced cancer immunotherapy.
• To investigate the efficacy of CAP-mediated ICB therapy delivered via microneedles (MN) in inhibiting tumor growth and improving survival in preclinical models.

Main Methods:

• A hollow-structured microneedle (hMN) patch was designed for transdermal delivery of CAP and anti-programmed death-ligand 1 antibody (aPDL1).
• The hMN patch facilitated CAP penetration, inducing tumor cell death and releasing tumor-associated antigens.
• This promoted dendritic cell maturation and T cell-mediated immune responses, augmented by the released aPDL1.

Main Results:

• The integrated CAP and ICB therapy via hMN patch demonstrated significant inhibition of primary and distant tumor growth in mice.
• The treatment led to prolonged survival in tumor-bearing mice, indicating robust systemic antitumor immunity.
• The hMN patch effectively delivered CAP and aPDL1, triggering a cascade of immune responses.

Conclusions:

• Transdermal delivery of combined CAP and ICB therapy using microneedles represents a promising strategy to overcome current limitations in cancer immunotherapy.
• This innovative approach enhances antitumor immunity and effectively controls tumor progression, offering a potential new avenue for clinical application.