Localized photothermal–chemotherapy synergy via Bi2S3 and sorafenib co-loaded dissolvable microneedles: a non-invasive precision delivery approach for melanoma suppression

Abstract

Skin cancer, particularly melanoma, is currently treated through various approaches, including surgery, radiotherapy, and chemotherapy. However, these methods have significant limitations and cause severe side effects. This underscores the pressing need for more effective therapies. Given that this disease appears on the skin surface, it is imperative to have a therapeutic system for topical drug delivery while minimizing systemic distribution. Microneedling is a novel transdermal drug delivery system that creates micropores on the skin surface to bypass the stratum corneum and achieve successful drug delivery to the skin sublayers, in a non-invasive manner. In this study, a dissolvable microneedle (MN) patch is created using polyvinylpyrrolidone (PVP), a water-soluble, biocompatible, and biodegradable polymer. Bismuth sulfide (Bi₂S₃) nanoparticles (NPs), as a photothermal therapy (PTT) agent, and sorafenib (SFN) for chemotherapy against cancer are co-encapsulated within the MN patch. The Bi₂S₃-SFN-loaded MN arrays exhibit strong mechanical properties for skin insertion, enabling them to penetrate tumors, dissolve, and release their therapeutic cargos directly within the tumor tissue. Upon exposure to an NIR laser, Bi₂S₃ NPs exhibit a photothermal effect, effectively inhibiting cancer cell proliferation. When combined with the chemotherapeutic capability of SFN, this approach shows great promise in achieving complete tumor suppression. In addition, the local administration of the MNs results in high biosafety and biocompatibility toward healthy tissues in vivo.