RESUMO
The rapid development of antimicrobial resistance due to broad antibiotic utilisation in the healthcare and food industries and the non-availability of novel antibiotics represents one of the most critical public health issues worldwide. Current advances in nanotechnology allow new materials to address drug-resistant bacterial infections in specific, focused, and biologically safe ways. The unique physicochemical properties, biocompatibility, and wide range of adaptability of nanomaterials that exhibit photothermal capability can be employed to develop the next generation of photothermally induced controllable hyperthermia as antibacterial nanoplatforms. Here, we review the current state of the art in different functional classes of photothermal antibacterial nanomaterials and strategies to optimise antimicrobial efficiency. The recent achievements and trends in developing photothermally active nanostructures, including plasmonic metals, semiconductors, and carbon-based and organic photothermal polymers, and antibacterial mechanisms of action, including anti-multidrug-resistant bacteria and biofilm removal, will be discussed. Insights into the mechanisms of the photothermal effect and various factors influencing photothermal antimicrobial performance, emphasising the structure-performance relationship, are discussed. We will examine the photothermal agents' functionalisation for specific bacteria, the effects of the near-infrared light irradiation spectrum, and active photothermal materials for multimodal synergistic-based therapies to minimise side effects and maintain low costs. The most relevant applications are presented, such as antibiofilm formation, biofilm penetration or ablation, and nanomaterial-based infected wound therapy. Practical antibacterial applications employing photothermal antimicrobial agents, alone or in synergistic combination with other nanomaterials, are considered. Existing challenges and limitations in photothermal antimicrobial therapy and future perspectives are presented from the structural, functional, safety, and clinical potential points of view.
Assuntos
Anti-Infecciosos , Hipertermia Induzida , Nanoestruturas , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Nanoestruturas/uso terapêutico , Nanoestruturas/química , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antibacterianos/química , NanotecnologiaRESUMO
BACKGROUND: Currently available anti-leukemia drugs have shown limited success in the treatment of acute myeloid leukemia (AML) due to their poor access to bone marrow niche supporting leukemic cell proliferation. RESULTS: Herein, we report a bone marrow-targetable green tea catechin-based micellar nanocomplex for synergistic AML therapy. The nanocomplex was found to synergistically amplify the anti-leukemic potency of sorafenib via selective disruption of pro-survival mTOR signaling. In vivo biodistribution study demonstrated about 11-fold greater bone marrow accumulation of the nanocomplex compared to free sorafenib. In AML patient-derived xenograft (AML-PDX) mouse model, administration of the nanocomplex effectively eradicated bone marrow-residing leukemic blasts and improved survival rates without noticeable off-target toxicity. CONCLUSION: This study may provide insights into the rational design of nanomedicine platforms enabling bone marrow-targeted delivery of therapeutic agents for the treatment of AML and other bone marrow diseases.
Assuntos
Catequina , Leucemia Mieloide Aguda , Camundongos , Animais , Humanos , Medula Óssea , Catequina/farmacologia , Micelas , Sorafenibe , Distribuição Tecidual , Leucemia Mieloide Aguda/tratamento farmacológico , Modelos Animais de Doenças , CháRESUMO
(-)-Epigallocatechin-3-O-gallate (EGCG), the most bioactive catechin in green tea, has drawn significant interest as a potent antioxidant and anti-inflammatory compound. However, the application of EGCG has been limited by its rapid autoxidation at physiological pH, which generates cytotoxic levels of reactive oxygen species (ROS). Herein, we report the synthesis of poly(acrylic acid)-EGCG conjugates with tunable degrees of substitution and their spontaneous self-assembly into micellar nanoparticles with enhanced resistance against autoxidation. These nanoparticles not only exhibited superior oxidative stability and cytocompatibility over native EGCG, but also showed excellent ROS-scavenging and anti-inflammatory effects. This work presents a potential strategy to overcome the stability and cytotoxicity issues of EGCG, making it one step closer toward its widespread application.