Photodynamic therapy with NIR-II probes: review on state-of-the-art tools and strategies.

In 2022 10% of the world's population was aged 65+, and by 2100 this segment is expected to hit 25%. These demographic changes place considerable pressure over healthcare systems worldwide, which results in an urgent need for accurate, inexpensive and non-invasive ways to treat cancers, a family of diseases correlated with age. Among the therapeutic tools that gained important attention in this context, photodynamic therapies (PDT), which use photosensitizers to produce cytotoxic substances for selectively destroying tumor cells and tissues under light irradiation, profile as important players for next-generation nanomedicine. However, the development of clinical applications is progressing at slow pace, due to still pending bottlenecks, such as the limited tissue penetration of the excitation light, and insufficient targeting performance of the therapeutic probes to fully avoid damage to normal cells and tissues. The penetration depth of long-wavelength near infrared (NIR) light is significantly higher than that of short-wavelength UV and visible light, and thus NIR light in the second window (NIR-II) is acknowledged as the preferred phototherapeutic means for eliminating deep-seated tumors, given the higher maximum permissible exposure, reduced phototoxicity and low autofluorescence, among others. Upon collective multidisciplinary efforts of experts in materials science, medicine and biology, multifunctional NIR-II inorganic or organic photosensitizers have been widely developed. This review overviews the current state-of-the art on NIR-II-activated photosensitizers and their applications for the treatment of deep tumors. We also place focus on recent efforts that combine NIR-II activated PDT with other complementary therapeutic routes such as photothermal therapy, chemotherapy, immunotherapy, starvation, and gas therapies. Finally, we discuss still pending challenges and problems of PDT and provide a series of perspectives that we find useful for further extending the state-of-the art on NIR-II-triggered PDT.