Ye et al. developed a polymer-based transdermal microneedle patch loaded with whole tumor lysate, melanin, and GM-CSF that, in combination with near-infrared irradiation, increased survival and reduced growth of primary and distant tumors in mice with melanoma or triple-negative breast cancer. Upon irradiation, melanin generated local heat, leading to the production of inflammatory cytokines and danger signals that attracted adaptive (T and B) and innate (dendritic and NK) immune cells and initiated antigen-specific immune response.

Melanin is capable of transforming 99.9% of the absorbed sunlight energy into heat, reducing the risk of skin cancer. We here develop a melanin-mediated cancer immunotherapy strategy through a transdermal microneedle patch. B16F10 whole tumor lysate containing melanin is loaded into polymeric microneedles that allow sustained release of the lysate upon insertion into the skin. In combination with the near-infrared light irradiation, melanin in the patch mediates the generation of heat, which further promotes tumor-antigen uptake by dendritic cells, and leads to enhanced antitumor vaccination. We found that the spatiotemporal photoresponsive immunotherapy increases infiltration of polarized T cells and local cytokine release. These immunological effects increase the survival of mice after tumor challenge and elicited antitumor effects toward established primary tumor and distant tumor. Collectively, melanin generates local heat, boosts T cell activities by transdermal vaccines, and promotes antitumor immune responses.

Author Info: (1) Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USA. Division of Pharmacoenginee

Author Info: (1) Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USA. Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. (2) Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USA. Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. (3) Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USA. Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. (4) Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USA. Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. (5) Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USA. Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. (6) Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USA. Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. (7) Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USA. Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. (8) Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USA. (9) Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USA. Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA. (10) Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USA. Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. (11) Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. (12) Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USA. zgu@email.unc.edu. Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.