Pathogenic bacteria infections bring about a substantial risk to human health. Given the development of antibiotic-resistance bacteria, alternative antibacterial strategies with great inactivation efficiency and bacteria-binding ability are extremely attractive. In this work, a metabolic labeling photosensitizer, prepared by the coupling of commercial IR820 and Dpropargylglycine (a type of D-amino acid, DAA) via a straightforward one-step incubation (IR820-DAA), could metabolically be incorporated into the bacterial wall via enzymatic reactions, thus enhancing antibacterial efficiency. The laser energy at 808 nm could make IR820-DAA a synergistic photothermal/ photodynamic agent for efficient antibacterial therapy and wound healing. Furthermore, IR820-DAA exhibits good water solubility and biological safety for clinical translation and even possesses biofilm degradation activity toward methicillin-resistant Staphylococcus aureus (MRSA). Overall, the proposed IR820-DAA holds great promise as a nonantibiotic tool for the treatment of bacteria-related diseases and offers a blueprint for building the precise synergistic antibacterial therapeutic platform.

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Phototherapy is a conducive and non-invasive strategy for cancer therapy under light irradiation. Inspiringly, fluorescence imaging in the second near-infrared window (NIR-II, 1000–1700 nm) holds a great promise for imaging-guided phototherapy with deep penetration and high spatiotemporal resolution. However, most phototherapeutics still face great challenges, including complicated synthesis of agents, potential biotoxicity and unsatisfied therapeutic outcomes. Herein, a near-infrared laser triggered molecular photosensitizer FEPT, modified with triphenylphosphine PEGylation (PEG2000-TPP), is developed for NIR-II imaging-guided mitochondria-targeting synergistic photothermal therapy (PTT)/photodynamic therapy (PDT)/immune therapy (IMT). The mitochondria-targeting photosensitizer FEPT can produce reactive oxygen species (ROS) and hyperpyrexia upon 808 nm laser irradiation, resulting in mitochondrial dysfunction and photo-induced apoptosis via caspase-3 pathway. Phototherapy-induced hyperthermia or ROS triggers the release of immunogenic intracellular substrates from dying tumor cells, thereby promoting the activation of antitumor immunity. Herein, this work provides a practicable strategy to develop a molecular phototheranostic platform for imaging-guided cancer therapy via mitochondria-targeting. Graphical Abstract

Effectively interfering energy metabolism in tumor cells and simultaneously activating the in vivo immune system to perform immune attacks are meaningful for tumor treatment. However, precisely targeted therapy is still a huge challenge. Herein, a mitochondrial‐targeting phototheranostic system, FE‐T nanoparticles (FE‐T NPs) are developed to damage mitochondria in tumor cells and change the tumor immunosuppressive microenvironment. FE‐T NPs are engineered by encapsulating the near‐infrared (NIR) absorbed photosensitizer IR‐FE‐TPP within amphiphilic copolymer DSPE‐SS‐PEG‐COOH for high‐performing with simultaneous mitochondrial‐targeting, near‐infrared II (NIR‐II) fluorescence imaging, and synchronous photothermal therapy (PTT) /photodynamic therapy (PDT) /immune therapy (IMT). In tumor treatment, the disulfide in the copolymer can be cleaved by excess intracellular glutathione (GSH) to release IR‐FE‐TPP and accumulate in mitochondria. After 808 nm irradiation, the mitochondrial localization of FE‐T NPs generated reactive oxygen species (ROS), and hyperthermia, leading to mitochondrial dysfunction, photoinductive apoptosis, and immunogenic cell death (ICD). Notably, in situ enhanced PDT/PTT in vivo via mitochondrial‐targeting with FE‐T NPs boosts highly efficient ICD toward excellent antitumor immune response. FE‐T NPs provide an effective mitochondrial‐targeting phototheranostic nanoplatform for imaging‐guided tumor therapy.

In recent years, pathogenic infections have been a growing health threat due to the proliferation of drug-resistant bacteria, so photothermal therapy (PTT) has gained considerable interest in biological and medical fields, owing to its noninvasive and highly effective properties. However, it is hard to achieve selective bacteria targeting while generating a large amount of heat at infected sites. Cationic electrostatic interaction is considered to be a common antimicrobial strategy. Herein, an organic molecule named RT-MN was synthesized with four positively charged quaternary ammonium salts that can bind to negatively charged bacteria. Under near-infrared 808 nm laser irradiation, RT-MN could be efficiently converted into a large amount of heat to eradicate bacteria. In addition, its good water solubility and biological safety proved that RT-MN has excellent biological application prospects. Overall, four such positively charged photosensitizer RT-MN, as a non-antibiotic treatment for resistant bacteria, could be promising for the exploration of highly effective antibacterial agents.