Effective Photothermal Therapy Mediated By Indocyanine Green Nanoparticle Tip-Loaded Microneedles To Enhance Checkpoint Inhibitor Immunotherapy For Melanoma Treatment

Topical and targeted photothermal therapy (PTT) mediated by a microneedle system is a promising strategy to enhance checkpoint inhibitor immunotherapy in melanoma treatment by integrating the instant tumor ablation effect and persistent antitumor immune response. However, the amount of drug delivered into the tumor site by microneedles is limited by low drug loading efficiency and insufficient drug distribution in the microneedle tips. Here, a simple and ingenious microneedle design that makes use of nanotechnology and centrifugal force was developed for the effective loading of indocyanine green (ICG). ICG stability in aqueous solution was first improved by chitosan nanoparticle encapsulation and then mixed with oligomeric sodium hyaluronate, the microneedle matrix material, which increased the size of the nanoparticles and facilitated their enrichment in the microneedle tips under centrifugal force. The amount of ICG loaded into the designed microneedles was 7 times higher than that of the microneedles loaded directly with ICG without nanoparticle encapsulation. The higher drug loading amount and main distribution in the microneedle tips resulted in a higher transdermal delivery efficiency and finally contributed to better in vivo photothermal performance. An in vivo antitumor study showed that the combination of the designed microneedles and the previously established checkpoint inhibitor-loaded core-shell microneedle system exhibited instant tumor inhibition and a slower tumor growth rate in the later period, demonstrating a synergetic effect. Therefore, this microneedle system composed purely of clinically approved components is expected to have great potential for clinical translation to enhance checkpoint inhibitor immunotherapy.