Nanotechnology-Enhanced Photosensitizers: Review of Multifunctional Theranostics for Precision Medicine

Photodynamic therapy (PDT) is increasingly recognized worldwide as a major therapeutic modality for the management of cancer and infectious diseases. The success of PDT largely depends on the design and performance of photosensitizers (PSs) capable of generating reactive oxygen species (ROS) upon light activation. However, traditional PSs face challenges such as poor solubility, limited tissue penetration, non-specific accumulation, and phototoxicity. The objective of this study is to provide an updated synthesis of advancements in this evolving field; therefore, a narrative review was conducted.

An extensive literature search was conducted using electronic databases including PubMed, Scopus, Web of Science, and Google Scholar up to March 2024. Keywords such as "photodynamic therapy", "photosensitizers", "nanoparticles", "ROS", and "theranostics" were used to identify relevant literature, with emphasis on original research articles, reviews, and clinical studies.

This review highlights the evolution of photosensitizer systems, encompassing both natural and synthetic derivatives, and discusses how nanoparticle (NP)-based strategies such as up-conversion nanoparticles (UCNPs), lipid-based carriers, and polymeric systems have enhanced the therapeutic selectivity, ROS production, and tissue targeting of PDT. Particular attention is given to theranostic applications, combining imaging and therapy within a single platform. Furthermore, emerging clinical trials investigating PDT applications in cutaneous T-cell lymphoma, pancreatic cancer, systemic sclerosis, and head and neck cancers are summarized, illustrating the expanding translational potential of these technologies.

These advances show a clear transition from a localized cytotoxic modality in PDT towards a precision nanomedicine modality. Using multifunctional nanocarriers in combination with optimized photosensitizers improves treatment efficacy and reduces off-target damage. Real-time monitoring of treatment and personalization is also made possible by the emergence of theranostic platforms. Collectively, current clinical studies indicate that PDT will be an increasingly flexible and translational approach across diverse disease settings.

This review paper focuses on PDT with different classes of PSs, with a particular emphasis on nano-based applications at both therapeutic and diagnostic levels.