Melanoma is a highly invasive skin cancer, and its treatment faces challenges such as difficulty in penetrating the skin barrier with drugs and systemic side effects. As a unique transdermal drug delivery method, microneedles have many advantages such as painlessness, easy operation, and high patient compliance. However, the existing microneedle technology has problems such as shallow drug delivery depth and single treatment methods, which limit the application and promotion of this technology.

On July 11, 2024, Advanced Functional Materials reported that researchers have utilized a rocket microneedle drug delivery system that can achieve deep drug delivery through a self-propelled mechanism, demonstrating good efficacy in combination therapy for melanoma.

The upper layer of the microneedle (MN) system in this work is composed of mesoporous silica nanoparticles with photodynamic activity, characterized by covalent bonding of photosensitizers and loading of trametinib (TRA) into the mesopores. TRA is a targeted small molecule drug that targets melanoma cells with excessive activation of the MEK pathway. The lower layer of the microneedles is composed of enzyme cross-linked HA Tyr hydrogel and collagenase (CLG), which can act as a rocket booster to promote the deep penetration of nanoparticles by remodeling the extracellular matrix (ECM) of tumor tissue.

Researchers designed three types of microneedles, and test results showed that PcNP/TRA-HA-Tyr (II)/CLG-MN had the deepest penetration into tumor tissue and the longest retention time in vivo. Photodynamic therapy after administration can significantly inhibit the growth of A375 transplanted tumors in mice.

When the "rocket microneedle" penetrates the skin epidermis, the upper and lower layers of MN separate. The lower layer of MN expands under the skin to form hydrogel, which regulates the release of CLG, thus reshaping the compact ECM and promoting the diffusion and distribution of drugs. Meanwhile, the mesoporous silica nanoparticles (PcNP/TRA) in the upper layer of MN penetrate deep into the tumor and are internalized by melanoma cells.

On the one hand, TRA targets the over activated MEK pathway in melanoma cells, reducing the phosphorylation level of ERK kinase. On the other hand, Pc Si responds to external infrared light stimulation to generate reactive oxygen species, achieving PDT therapy for melanoma. Ultimately, targeted therapy and PDT therapy work together to efficiently kill tumor cells and inhibit melanoma growth.

This study provides a new approach for deep penetration of drugs and combined treatment of melanoma, and offers new ideas for the application of microneedle technology in the treatment of important diseases.

From Article:A Multifunctional Rocket-Like Microneedle System with Thrusters for Self-Promoted Deep Drug Penetration and Combination Treatment in Melanoma

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