Effective Photothermal Therapy Mediated by Indocyanine Green Nanoparticle Tip-Loaded Microneedles to Enhance Checkpoint Inhibitor Immunotherapy for Melanoma Treatment

Abstract

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.

Persistent Production of Reactive Oxygen Species with Zn2GeO4:Cu Nanorod-Loaded Microneedles for Methicillin-Resistant Staphylococcus Aureus Infectious Wound Healing

“…To prepare ZGC@MNs, MNs with pyramidal tips were opted to load ZGC due to the sharp shape conducive to piercing the stratum corneum. PVA was employed as the MN backing layer material and NaHA was employed as the MN tip material for its superior moisturizing effect and characteristics of promoting cell movement and proliferation. − A NaHA solution containing ZGC was introduced to the mold and placed under vacuum to make the dispersion fill the tip cavity (Figure a). After the removal of redundant dispersion, the mold was dried and the abovementioned process was repeated three times to concentrate the tip solution.…”

Biomaterials for enhanced immunotherapy

“… 73 Later, indocyanine green, a photosensitizer used in photothermal therapy was added to further stimulate the anti-tumor immune response. 74 These microneedles had an even greater anti-tumor effect and a further survival increase compared to the previous microneedles.…”

Microneedle-mediated treatment for superficial tumors by combining multiple strategies

“…In recent years, to deal with the occurrence of various skin cancers, synergy strategy [ 85 , 86 ], drug function modification strategy [ 87 ], spatiotemporal controllable drug release strategy [ 50 , 73 , 88 ], local targeted drug delivery strategy, [ 5 , 89 ], and other methods have been developed. Among them, the local targeted therapy strategy has become a potential treatment mode due to its remarkable drug concentration and few side effects.…”