Light therapy, using photosensitizers and light to treat diseases, has been used clinically for various superficial diseases since 1903. While effective, current methods have drawbacks: intravenous photosensitizer injection leads to metabolic burden and potential harm to healthy tissues, while direct illumination necessitates high irradiance, causing pain and skin damage. The inconvenience of multiple hospital visits also compromises patient compliance. Transdermal delivery of photosensitizers or light offers a potential solution. While transdermal photosensitizer delivery has shown promise, transdermal light delivery is less developed, and simultaneous delivery of both remains unrealized. This research addresses these limitations by developing a miniaturized, all-in-one device for point-of-care light therapy.

Existing light therapies often involve intravenous photosensitizer administration and direct light application. This approach, while effective, presents significant challenges. Intravenous administration leads to photosensitizer accumulation in the circulatory system, causing metabolic stress and potential damage to healthy tissue due to the generation of reactive oxygen species (ROS) when activated by ambient light. Patients often require weeks of strict light shielding after treatment. Direct illumination requires higher light irradiance to compensate for energy loss in the stratum corneum, leading to pain and tissue damage. The need for bulky, expensive equipment further restricts accessibility. Transdermal delivery of photosensitizers, using methods like iontophoresis or microneedles, has shown success in treating conditions like actinic keratosis. However, transdermal light delivery is still in its early stages, with studies focusing primarily on biodegradable polymer waveguides. The concept of simultaneously delivering both photosensitizer and therapeutic light transdermally using a portable device has been proposed but not yet realized. The current study aims to fill this gap.

The researchers developed a Miniaturized all-in-one Light therapy Device (MiLD) using dual-function microneedles. These microneedles have dissolvable tips (loaded with photosensitizer) and transparent needle bodies (acting as light guides). The MiLD, measuring 2 cm x 1.7 cm x 1.2 cm and weighing 3.6 g, incorporates an LED array, a control circuit, and a battery. The device is wirelessly controlled via Bluetooth. The fabrication process involved creating a copper microneedle master, using this to create a PDMS mold, and then sequentially pouring photosensitizer-loaded HA solution (for the tips) and PVA solution (for the bodies) into the mold, followed by attachment of the LED array. A graphene membrane dissipates heat. The device's performance was characterized using various methods, including Monte Carlo simulations to model light distribution within the skin. The efficacy of MiLD-mediated photodynamic therapy (PDT) in removing disordered tissue (using port wine stains in a mouse model) and photochemical tissue bonding (PTB) in promoting healthy tissue growth (wound repair in mice) was evaluated. Histopathological analysis, qRT-PCR (to assess IL1 expression), and LC/MS/MS (to quantify HMME levels in blood) were employed to assess tissue damage and photosensitizer accumulation. The biocompatibility and safety profile of MiLD was also evaluated. Statistical analysis included unpaired Student's t-tests.

The MiLD successfully delivered both photosensitizer and light transdermally, achieving therapeutic effects comparable to traditional PDT in both tissue removal and tissue growth applications. In the PDT experiments, MiLD-mediated treatment (using 0.75 µg HMME and 20 mW cm⁻² irradiance) resulted in vascular area reduction comparable to traditional PDT (using 300 µg HMME and 80 mW cm⁻² irradiance). MiLD significantly reduced the irradiance needed for PDT, lessening the associated tissue damage and inflammation (evidenced by H&E staining and IL1 mRNA expression). Notably, MiLD completely eliminated photosensitizer accumulation in the bloodstream (as confirmed by LC/MS/MS), unlike intravenous administration. In the PTB experiments, MiLD (using 22.5 µg RB and 40 mW cm⁻² irradiance) achieved faster and better wound closure than direct application of RB and light at higher irradiance. Monte Carlo simulations demonstrated superior light penetration with MiLD compared to direct illumination due to reduced scattering and absorption in the stratum corneum. The device showed excellent biocompatibility, causing minimal skin damage.

The MiLD addresses critical limitations of current light therapy methods. The miniaturized, all-in-one design and user-friendly operation make it suitable for point-of-care applications. The significant reduction in photosensitizer dosage and light irradiance substantially reduces adverse effects. The effective transdermal delivery eliminates systemic photosensitizer accumulation and mitigates light-induced tissue damage. The results demonstrate the potential of MiLD to improve the safety and accessibility of light therapy, particularly for treating superficial diseases.

The MiLD represents a significant advance in light therapy, offering a safe, effective, and convenient point-of-care solution. Its miniaturization, ease of use, and ability to minimize adverse effects overcome many limitations of traditional methods. Future research could focus on expanding the range of treatable conditions, optimizing the device's design and materials, and conducting larger-scale clinical trials.

The study primarily utilized a mouse model. Further investigation is needed to confirm the findings in larger animal models and ultimately, in human clinical trials. The long-term effects of MiLD application on skin tissue remain to be thoroughly assessed. The generalizability of the findings to different types of light therapy and photosensitizers also requires further investigation.