Nano-photosensitizers for enhanced photodynamic therapy

Photodynamic therapy (PDT) utilizes photosensitizers (PSs) together with irradiation light of specific wavelength interacting with oxygen to generate cytotoxic reactive oxygen species (ROS), which could trigger apoptosis and/or necrosis-induced cell death in target tissues. During the past two decades, multifunctional nano-PSs employing nanotechnology and nanomedicine developed, which present not only photosensitizing properties but additionally accurate drug release abilities, efficient response to optical stimuli and hypoxia resistance. Further, nano-PSs have been developed to enhance PDT efficacy by improving the ROS yield. In addition, nano-PSs with additive or synergistic therapies are significant for both currently preclinical study and future clinical practice, given their capability of considerable higher therapeutic efficacy under safer systemic drug dosage. In this review, nano-PSs that allow precise drug delivery for efficient absorption by target cells are introduced. Nano-PSs boosting sensitivity and conversion efficiency to PDT-activating stimuli are highlighted. Nano-PSs developed to address the challenging hypoxia conditions during PDT of deep-sited tumors are summarized. Specifically, PSs capable of synergistic therapy and the emerging novel types with higher ROS yield that further enhance PDT efficacy are presented. Finally, future demands for ideal nano-PSs, emphasizing clinical translation and application are discussed.