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

Near-infrared-II (NIR-II) bioimaging gradually becomes a vital visualization modality in the real-time investigation for fundamental biological research and clinical applications. The favorable NIR-II contrast agents are vital in NIR-II imaging technology for clinical translation, which demands good optical properties and biocompatibility. Nevertheless, most NIR-II contrast agents cannot be applied to clinical translation due to the acute or chronic toxicity caused by organ retention in vivo imaging. Therefore, it is critical to understand the pharmacokinetic properties and optimize the clearance pathways of NIR-II contrast agents in vivo to minimize toxicity by decreasing organ retention. In this review, the clearance mechanisms of biomaterials, including renal clearance, hepatobiliary clearance, and mononuclear phagocytic system (MPS) clearance, are synthetically discussed. The clearance pathways of NIR-II contrast agents (classified as inorganic, organic, and other complex materials) are highlighted. Successively analyzing each contrast agent barrier, this review guides further development of the clearable and biocompatible NIR-II contrast agents.

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