Shortwave infrared imaging–guided radiosensitization using rare-earth-doped nanoparticles delivered via microneedles for enhanced melanoma therapy

Melanoma remains a major global health challenge due to the uncontrolled growth of abnormal skin cells, resistance to conventional therapies, and poor prognosis in advanced cases. Localized, early-stage melanoma, defined as melanoma confined to the skin without regional or distant spread, offers a critical treatment window, as thin lesions are often curable with surgical excision. However, delays in treatment allow progression to lymph node involvement and distant metastasis, which worsen prognosis and limit available therapies. Although surgery and radiotherapy remain standard options, they often struggle with limitations like incomplete melanoma targeting, damage to healthy tissues, and treatment resistance. To address these challenges, we explored a more precise radiotherapy approach aimed at enhancing treatment efficacy while minimizing harm to surrounding tissues. In this study, we investigated the potential of rare-earth-doped nanoparticles (RENPs) as radiosensitizers by integrating them with microneedles (MNs) and shortwave infrared (SWIR) imaging to improve the precision of radiotherapy for localized, early-stage melanoma treatment. RENPs were synthesized using a modified thermal decomposition method and surface-modified them with Tween 20 (Tw) to facilitate their transition into the aqueous phase for biological applications. Incorporating RENP-Tw into MNs enabled precise and localized delivery into melanoma tissue. Meanwhile SWIR imaging, with its deep tissue penetration and high contrast resolution, allowed real-time monitoring of RENP-Tw localization, ensuring optimal radiosensitization at the melanoma site. Our<i>in vivo</i>studies demonstrated that RENP-Tw/MNs significantly enhanced radiation-induced cell death in melanoma-bearing mice while minimizing systemic toxicity. Moreover, SWIR imaging revealed sustained luminescence of RENP-Tw/MNs at the melanoma site, further supporting precise radiotherapy with improved therapeutic outcomes. This innovative approach addresses the limitations of conventional radiotherapy by improving melanoma specificity, reducing off-target effects, and enhancing radiosensitization efficiency. Overall, our findings suggest that RENP-Tw/MNs hold potential as an effective strategy for advancing localized, early-stage melanoma treatment through precise, imaging-guided radiotherapy.