Development of dual-function optical microneedle lens array for skin cancer treatment by photodynamic therapy.

Abstract

Skin cancer is among the most prevalent cancers worldwide, with melanoma accounting for most skin cancer-related deaths owing to its aggressiveness and metastatic potential. Although treatments including surgery, radiotherapy, immunotherapy, and targeted therapy have improved outcomes, therapeutic limitations persist, particularly in locally advanced or recurrent disease. Photodynamic therapy (PDT), which combines a photosensitizer (PS), light activation, and oxygen to produce reactive oxygen species (ROS) inducing tumor cell death and antitumor immunity, offers a minimally invasive treatment alternative. Despite its clinical success for superficial basal cell carcinoma, PDT efficacy declines for lesion with increased thickness due to a poor PS and limited light penetration through the heterogeneous skin structure. To address these challenges, microneedles (MNs) have emerged as an effective drug delivery tool that can bypass the stratum corneum. Solid, transparent MNs can also guide and concentrate light. Previous studies have suggested combining MNs with lens arrays (optical microneedle lens array, OMLA) to enhance light delivery deeper into the tissues. In this study, we present a novel OMLA device that integrates aligned lenses and coated MNs for the dual delivery of the PS and light. An OMLA fabricated from polylactic-acid (PLA) <i>via</i> hot embossing was mechanically characterized for insertion capability. Computational analysis was used to evaluate light propagation properties, which were validated in an <i>ex vivo</i> human NativeSkin® model. Additionally, we coated two clinically relevant PSs, 5-aminolevulinic acid and rose bengal. Finally, we demonstrated that a PS-coated OMLA effectively delivered both light and the PS, resulting in effective PDT-induced cytotoxicity in 2D and 3D melanoma cell models.