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.