Localized early-stage melanoma remains challenging to treat because of limited therapeutic precision, intrinsic radioresistance, and the risk of off-target toxicity associated with conventional treatment approaches. Emerging nanotheranostic strategies offer opportunities to integrate imaging and therapy; however, limitations involving insufficient spatial confinement, lack of real-time therapeutic feedback, and incomplete mechanistic coordination continue to restrict therapeutic precision and translational applicability. Here, a nanotheranostic framework is proposed in which a DSPE-PEG–mediated hybrid system integrates lanthanide upconversion nanoparticles and carbon-based photothermal nanomaterials for combined short-wave infrared (SWIR) imaging, photothermal therapy, and radiosensitization, delivered through dissolving microneedle arrays for localized administration. The proposed system is designed to facilitate spatially confined, image-guided, and multimodal therapeutic activation while potentially minimizing systemic exposure. Within this framework, photothermal activation and radiosensitization are hypothesized to function within a coordinated therapeutic microenvironment, potentially supporting localized therapeutic coordination with the potential to improve treatment precision. Quantitative evaluation strategies are further proposed through photothermal profiling, radiation dose-response analysis, and synergy assessment using combination index and radiation enhancement ratio models. The proposed framework aims to integrate localized delivery, imaging-guided monitoring, and coordinated multimodal therapeutic interaction within a single therapeutic microenvironment, while potentially reducing systemic exposure and supporting more precise therapeutic intervention strategies for localized disease management. This approach may also support future optimization of adaptive therapeutic strategy development. Collectively, the present hypothesis proposes a system-level conceptual framework intended to support future experimental investigation and translational development.
Khan et al. (Mon,) studied this question.