Journal Article Ahead of print 1 citation
PubMed: 42522590 DOI: 10.1039/d5lc01169h
Development of dual-function optical microneedle lens array for skin cancer treatment by photodynamic therapy.
Lab Chip
Authors: Anthony Lefebvre, Wataru Hanamoto, Jongho Park, Pascal Deleporte, Anne-Sophie Dewalle, Vincent Senez, Orégane Bajeux, Nicolas Stoup, Guillaume Paul Grolez, Laurent Mortier, Nadira Delhem, Beomjoon Kim
Affiliations
- Institute of Industrial Science, The University of Tokyo, Tokyo, Japan.
- Department of Precision Engineering, The University of Tokyo, Tokyo, Japan.
- Univ. Lille, CHU Lille Inserm, U1366 - CRC Lille CNRS UMR 9020, ONCOTHAI - Assisted Laser Therapy and Immunotherapy for Oncology, Lille, France.
- Univ. Lille, CHU Lille Inserm, University Picardie Jules Verne, CNRS, U1366-UMR 9020 - Cancer Research Center of Lille, F-59000 Lille, France.
- Dermatology Department, University of Lille, CHU Lille, 59000 Lille, France.
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) via hot embossing was mechanically characterized for insertion capability. Computational analysis was used to evaluate light propagation properties, which were validated in an ex vivo 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.
MeSH
Skin, Cells, Photochemotherapy, Melanoma, Neoplasms, Therapeutics, Nanotechnology, Skin Neoplasms, Microneedle Drug Delivery