Enhancing melanoma therapy with hydrogel microneedles

Abstract

Melanoma is highly invasive and resistant to conventional treatments, accounting for nearly 75% of skin cancer-related deaths globally. Traditional therapies, such as chemotherapy and immunotherapy, often exhibit limited efficacy and are associated with significant side effects due to systemic drug exposure. Microneedles (MNs), as an emerging drug delivery system, offer multiple advantages, including safety, painlessness, minimal invasiveness, and controlled drug release. Among these, hydrogel microneedles (HMNs) stand out due to their extracellular matrix-like structure and swelling-induced continuous hydrogel channels, which enable the direct delivery of therapeutic agents into the tumor microenvironment (TME). This approach enhances drug bioavailability while reducing systemic toxicity, establishing HMNs as a promising platform for melanoma treatment. This review highlights recent advancements in HMNs for melanoma therapy, focusing on their applications in biomarker extraction for early diagnosis and their role in supporting multimodal treatment strategies, such as chemotherapy, immunotherapy, phototherapy, targeted therapy, and combination therapy. Furthermore, the current matrix materials and fabrication techniques for HMNs are discussed. Finally, the limitations of HMNs in melanoma treatment are critically analyzed, and recommendations for future research and development are provided.

Keywords: cancer therapy; controlled release; drug delivery systems; hydrogel microneedles; melanoma.

Figure 1

Structure and drug release mechanisms of various MN types.

Figure 2

The applications of HMNs in melanoma diagnosis and therapy.

Figure 3

Schematic illustration of the HMN patch for melanoma diagnosis. (i) ISF is extracted using the microneedle patch, (ii) eluted into a centrifuge tube, (iii) where S100A1 binds to MMPs and PMPs, and (iv) its concentration is quantified by measuring PMP accumulation. Copyright permission from Wang et al. (97), Advanced Science, 2024.

Figure 4

Schematic design of the MN patch for chemotherapy and characterization of Pd-TNSs.(a) Schematic illustration of bioorthogonal catalysis; (b) transmission electron microscope images of TNSs and (c) Pd-TNSs; (d) elemental mapping analysis of Pd-TNSs; (e) structural characterization of palladium in Pd-TNSs through extended X-ray absorption fine structure (EXAFS); (f) schematic representation of the decaging process; (g) fluorescence intensity measurements for monitoring drug activation and release. Copyright permission from Chen et al. (100), Nature Nanotechnology, 2021.

Figure 5

Schematic representation of the microneedle platform designed for CpG-ODN delivery and concurrent extraction of ISF. Copyright permission from Dosta et al. (101), Theranostics, 2023.

Figure 6

Schematic representation of HMNs for targeted melanoma therapy. Copyright permission from Xing et al. (106), International Journal of Pharmaceutics, 2024.

Figure 7

Schematic representation of HMNs for PDT in melanoma treatment. Copyright permission from Li et al. (104), American Chemical Society, 2022.

Figure 8

Schematic representation of a HMN platform for synergistic chemotherapy and photocatalytic therapy in the treatment of melanoma. Copyright permission from Yu et al. (105), Nano Letters, 2024.

Figure 9

Schematic representation of a HMN platform for immune synergistic therapy in melanoma ablation and subsequent skin regeneration. Copyright permission from Zhang et al. (107), International Journal of Biological Macromolecules, 2024.