The emergence of multi-drug-resistant pathogens threatens the healthcare systems world-wide. Recent advances in phototherapy (PT) approaches mediated by photo-antimicrobials (PAMs) provide new opportunities for the current serious antibiotic resistance. During the PT treatment, reactive oxygen species or heat produced by PAMs would react with the cell membrane, consequently leaking cytoplasm components and effectively eradicating different pathogens like bacteria, fungi, viruses, and even parasites. This Perspective will concentrate on the development of different organic photo-antimicrobials (OPAMs) and their application as practical therapeutic agents into therapy for local infections, wound dressings, and removal of biofilms from medical devices. We also discuss how to design highly efficient OPAMs by modifying the chemical structure or conjugating with a targeting component. Moreover, this Perspective provides a discussion of the general challenges and direction for OPAMs and what further needs to be done. It is hoped that through this overview, OPAMs can prosper and will be more widely used for microbial infections in the future, especially at a time when the global COVID-19 epidemic is getting more serious.

Hypochlorous acid (HOCl) acts as a weak acid distributed mainly in acidic organelle lysosomes of phagocytes and plays a crucial role in the immune defense. The elaborate interrelation between the variations of HOCl levels in lysosomes and different physiological and pathological processes remains unclear. Thus, the accurate determination of lysosomal HOCl in living cells and in vivo is very important. Because of extremely low concentration and difficulty in distinguishing HOCl from OCl under the physiological environment, it is still a great challenge to specifically monitor the intracellular intrinsic HOCl levels without exogenous stimulation, which impedes an exact understanding of its biological roles. In this paper, based on the electrophilic addition of Cl to sulfide moiety, we have developed a two-photon fluorescent probe O-(N-butyl-1,8-naphthalimide)-4-yl-N,N-dimethylthiocarbamate (NDMTC) for the specific determination of HOCl over OCl and other bioactive molecules. Our results show that NDMTC possesses a detection limit of 7.6 pM, and it is the first fluorescent probe for detecting HOCl at the picomolar level. Furthermore, by introducing an alkylmorpholine group to the NDMTC framework, the lysosome-targetable derivative Lyso-NDMTC was obtained, and its ability to image HOCl in the lysosome organelles was clearly confirmed. Combined with two-photon fluorescence imaging of background suppression and deeper tissue penetration, NDMTC and Lyso-NDMTC were used to successfully visualize intracellular native HOCl and discern tumor tissue in mice. This study offers two perfect fluorescence imaging probes for further investigation of pathological roles of HOCl in various diseases.

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