pH Reversibly Switchable Nanocapsule for Bacteria-Targeting Near-Infrared Fluorescence Imaging-Guided Precision Photodynamic Sterilization.

Photodynamic sterilization is the most promising method to combat bacterial infection, especially multidrug-resistant bacterial infection. However, the absorption of conventional photosensitizers is mostly located in the UV-vis region, leading to limited penetration depth and poor therapeutic efficacy for deep-tissue bacterial infection. Besides, most of the photosensitizers are always in the activated state and lack bacteria-targeting ability, which inevitably causes severe nonspecific damage to normal tissues. Here, we show the design of a pH reversibly switchable near-infrared photosensitizer-based nanocapsule for precision bacteria-targeting fluorescence imaging-guided photodynamic sterilization. pH reversibly activatable asymmetric cyanine was synthesized as a bacteria-specific imaging unit and smart photosensitizer to realize precision imaging-guided targeting sterilization without side effects. An allicin mimic was introduced into the smart photosensitizer as the auxiliary bactericidal group to further enhance antibacterial efficiency. Meanwhile, amphipathic functionalized polyethylene glycol was employed to fabricate the nanocapsule by self-assembly to endow the charge-reversed intelligent targeting ability and prolong blood circulation. The developed switchable nanocapsule not only enables precision bacterial infection-targeted imaging without background fluorescence interference but also gives an efficient bactericidal effect with excellent specificity and negligible side effects, holding great potential for practical application.

A pH reversibly activatable NIR photothermal/photodynamic-in-one agent integrated with renewable nanoimplants for image-guided precision phototherapy.

Phototherapy has great potential to revolutionize conventional therapeutic modalities. However, most phototherapeutic strategies based on multicomponent therapeutic agents generally lack tumor-specificity, resulting in asynchronous therapy and superimposed side-effects. Severe heat damage is also inevitable because of the necessity of continuous external irradiation. Here we show the design of an acid-activated and continuous external irradiation-free photothermal and photodynamic (PTT/PDT) synchronous theranostic nanoplatform for precision tumor-targeting near-infrared (NIR) image-guided therapy. pH-reversibly responsive brominated asymmetric cyanine is designed as the tumor-specific NIR PTT/PDT-in-one agent to enhance anticancer efficiency and reduce side-effects. Ultra-small NIR persistent luminescence nanoparticles are prepared as both the imaging unit and renewable nanoimplant. Biotin functionalized polyethylene glycol is introduced to endow active tumor-targeting ability and prolong blood-circulation. The developed smart platform offers merits of reversible activation, PTT/PDT synergetic enhancement, tumor targetability and continuous external irradiation-free properties, allowing autofluorescence-free image-guided phototherapy only in tumor sites. This work paves the way to developing smart theranostic nanoplatforms for precision medicine.