Light-Activable On-Demand Release of Nano-Antibiotic Platforms for Precise Synergy of Thermochemotherapy on Periodontitis

The overprescription and improper use of antibiotics have contributed to the evolution of bacterial resistance, making it urgent to develop alternative therapies and agents with better efficacy as well as less toxicity to combat bacterial infections and keep new resistance from developing. In this work, a novel light-activable nanoantibiotic platform (TC-PCM@GNC-PND) was constructed by the incorporation of gold nanocages (GNC) and two thermosensitive gatekeepers, phase-change materials (PCM) and thermosensitive polymer poly(N-isopropylacrylamide-co-diethylaminoethyl methacrylate) (PND), to realize precisely the synergy of photothermal and antimicrobial drugs. GNC exhibits an excellent photothermal effect owing to its strong absorbance in the near-infrared (NIR) region, and hollow interiors make it a favorable vehicle for loading various antibiotics such as tetracycline (TC). The release of the encapsulated drugs could be precisely controlled by NIR light through the dual thermosensitive interaction of liquid-solid transition of PCM and coil- granule transition of PND, improving efficacy and alleviating side effects with on-demand drug release. The thermosensitive hydrogel was formed in situ upon application with body temperature, enhancing retention of the antimicrobial agent in local infectious sites. Highly effective ablation of bacteria is achieved both in vitro and in periodontitis models with little toxicity owing to the synergy of photothermal effects and chemotherapeutic drug release induced by NIR. This study could provide guidance for the design of antibacterial materials and shed substantial light on synergistic treatment.