Lysosome-Targeting Aggregation-Induced Emission Nanoparticle Enables Adoptive Macrophage Transfer-Based Precise Therapy of Bacterial Infections

Abstract

Traditional antibacterial procedures are getting inefficient due to the emergence of antimicrobial resistance, which makes alternative treatments in urgent demand. However, the selectivity toward infectious bacteria is still challenging. Herein, by taking advantage of the self-directed capture of infectious bacteria by macrophages, we developed a strategy to realize precise in vivo antibacterial photodynamic therapy (APDT) through adoptive photosensitizer-loaded macrophage transfer. TTD with strong reactive oxygen species (ROS) production and bright fluorescence was first synthesized and was subsequently formulated into TTD nanoparticles for lysosome targeting. TTD-loaded macrophages (TLMs) were constructed by direct incubation of TTD nanoparticles with macrophages, in which the TTD was localized in the lysosomes to meet the captured bacteria in the phagolysosomes. The TLMs could precisely capture and eradicate bacteria while being activated toward the proinflammatory and antibacterial M1 phenotype upon light illumination. More importantly, after subcutaneous injection, TLMs could effectively inhibit bacteria in the infected tissue through APDT, leading to good tissue recovery from severe bacterial infection. Overall, the engineered cell-based therapeutic approach shows great potential in the treatment of severe bacterial infectious diseases.

Role of lysosome in healing neurological disorders by nano-bioengineering

“…Recently nano-bioengineered macrophage in therapeutically tackling bacterial-infections in a transfer-based approach shows great clinical impact, which can be extrapolated to the neurodegeneration field. Directed delivery of drugs/proteinaceous/genetic-materials to the endolysosomal-systems or to the affected cell population niche can be programmed by exploiting the over-active engulfment-endocytotic-exocytotic property of macrophages, which are triggered by immuno-inflammation during infection, injury and neurodegeneration ( Huang et al, 2022 ; Wang et al, 2023 ). In support, recently intravenous administration of macrophages carrying particular gene-modifying nanoparticles within their endolysosomal compartments has been shown to be efficiently targeted to the PD-affected inflamed mouse brain-regions to ensure local delivery ( Haney et al, 2020 ).…”

Biomimetic Bacterium-like Particles Loaded with Aggregation-Induced Emission Photosensitizers as Plasma Coatings for Implant-Associated Infections

“…An ideal antibacterial strategy should be effective against a broad spectrum of bacteria but exhibit minimal side effects. − Antibacterial coatings can eradicate biofilm formation and prevent bacterial infections but are often effective only for a short period. , Stimuli-responsive coatings which can either inherently identify and destroy biofilm on the surface of the implant or render antibacterial action when triggered by stimuli such as pH, light, etc., can prevent IAIs for an extended duration. , Such coatings can be designed using layer-by-layer assembly, spin coating, plasma polymerization, dip coating, self-assembly, etc. , Among these, plasma polymerization is a substrate-independent technique to generate functional coatings for various biomedical applications . A nanothin layer of plasma polymers with reactive functional moieties will be deposited on the substrates via this technique, which can actively conjugate biomolecules, nanoparticles, and other bioactive substances .…”

Fast and Stable Antibacterial Coating of Photosensitive Aggregation‐Induced Emission Luminogens for Disinfection on Medical Devices

“…Photodynamic therapy (PDT) is an effective and alternative therapeutic strategy with high safety, noninvasiveness, and low drug resistance. [19][20][21] It has been successfully applied to the antibacterial applications for controlling MDR bacterial infections. [22][23][24] PDT generally combines photosensitizer with its photochemical reaction to generate biotoxic reactive oxygen species (ROS) under specific light irradiation.…”