The commercial antibiotics with inherent AIE feature: In situ visualization of antibiotic metabolism and specifically differentiation of bacterial species and broad-spectrum therapy.

The research on pharmacology usually focuses on the structure-activity relationships of drugs, such as antibiotics, to enhance their activity, but often ignores their optical properties. However, investigating the photophysical properties of drugs is of great significance because they could be used to in situ visualize their positions and help us to understand their working metabolism. In this work, we identified a class of commercialized antibiotics, such as levofloxacin, norfloxacin, and moxifloxacin (MXF) hydrochloride, featuring the unique aggregation-induced emission (AIE) characteristics. By taking advantage of their AIE feature, antibiotic metabolism in cells could be in situ visualized, which clearly shows that the luminescent aggregates accumulate in the lysosomes. Moreover, after a structure-activity relationship study, we found an ideal site of MXF to be modified with a triphenylphosphonium and an antibiotic derivative MXF-P was prepared, which is able to specifically differentiate bacterial species after only 10 min of treatment. Moreover, MXF-P shows highly effective broad-spectrum antibacterial activity, excellent therapeutic effects and biosafety for S. aureus-infected wound recovery. Thus, this work not only discovers the multifunctionalities of the antibiotics but also provides a feasible strategy to make the commercialized drugs more powerful.

AIE-Active Antibiotic Photosensitizer with Enhanced Fluorescence in Bacteria Infected Cells and Better Therapy Effect toward Drug-Resistant Bacteria.

It is well-known that bacterial infections will induce a variety of diseases in the clinic. In particular, the emergence of drug-resistant bacteria has increased the threat to human health. The development of multiple modes of therapy will effectively fight against drug-resistant bacterial infections. In this work, we covalently attached an AIE photosensitizer to the antibiotic of moxifloxacin hydrochloride (MXF-HCl) and synthesized an antibiotic derivative, MXF-R, with pharmacological activity and photodynamic activation. In infected cells, MXF-R showed enhanced fluorescence after it specifically binds to bacteria; thus, in situ visualization of the bacteria was realized. Notably, through chemo- and photodynamic therapy, MXF-R exhibited better antibacterial activity than its parent antibiotic in rapid sterilization, and it achieved effective killing for moxifloxacin resistant bacteria. In addition, MXF-R shows a broad-spectrum antibacterial effect and could be used in the recovery therapy of infected wounds in mice, demonstrative of a significant therapeutic effect and good biological safety. Thus, as a promising multifunctional antibacterial agent, MXF-R will have tremendous potential in in situ visualization study and killing of drug-resistant bacteria. This work provides an innovative strategy for solving critical disease through the combination of materials and biomedical sciences.

Photo-Enhanced Chemotherapy Performance in Bladder Cancer Treatment via Albumin Coated AIE Aggregates.

The implementation of cisplatin-based neoadjuvant chemotherapy (NAC) plays a key role in conjunction with surgical resection in preventing bladder cancer progression and recurrence. However, the significant dose-dependent toxic side effects of NAC are still a major challenge. To solve this problem, we developed a photoenhanced cancer chemotherapy (PECC) strategy based on AIEgen ((E)-3-(2-(2-(5-(4-(diphenylamino)phenyl)thiophen-2-yl)vinyl)-1,1-dimethyl-1H-3λ4-benzo[e]indol-3-yl)propane-1-sulfonate), which is abbreviated as BITT. Multifunctional BITT@BSA-DSP nanoparticles (NPs) were employed with an albumin-based nanocarrier decorated with the cisplatin(IV) prodrug and loaded to produce strong near-infrared fluorescence imaging (NIR FLI), and they exhibited good photoenhancement performance via photodynamic therapy (PDT) and photothermal therapy (PTT). In vitro results demonstrated that BITT@BSA-DSP NPs could be efficiently taken up by bladder cancer cells and reduced to release Pt (II) under reductase, ensuring the chemotherapy effect. Furthermore, both in vitro and in vivo evaluation verified that the integration of NIR FL imaging-guided PECC efficiently promoted the sensitivity of bladder cancer to cisplatin chemotherapy with negligible side effects. This work provides a promising strategy to enhance the sensitivity of multiple cancers to chemotherapy drugs and even achieve effective treatments for drug-resistant cancers.