School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211816, PR China.
School of Pharmacy, Hainan Medical University, Haikou 571199, Hainan, China.
J Control Release. 2024 Aug;372:795-809. doi: 10.1016/j.jconrel.2024.06.068. Epub 2024 Jul 5.
Biofilms, particularly those formed by multiple bacterial species, pose significant economic and environmental challenges, especially in the context of medical implants. Addressing the urgent need for effective treatment strategies that do not exacerbate drug resistance, we developed a novel nanoformulation, Ce6&PMb@BPN, based on black phosphorus nanosheets (BPN) for targeted treatment of mixed-species biofilms formed by Acinetobacter baumannii (A. baumannii) and methicillin-resistant Staphylococcus aureus (MRSA).The formulation leverages polymyxin B (PMb) for bacterial targeting and chlorin e6 (Ce6) for photodynamic action. Upon near-infrared (NIR) irradiation, Ce6&PMb@BPN efficiently eliminates biofilms by combining chemotherapy, photodynamic therapy (PDT) and photothermal therapy (PTT), reducing biofilm biomass significantly within 30 min. In vivo studies on mice infected with mixed-species biofilm-coated catheters demonstrated the formulation's potent antibacterial and biofilm ablation effects. Moreover, comprehensive biosafety evaluations confirmed the excellent biocompatibility of Ce6&PMb@BPN. Taken together, this intelligently designed nanoformulation holds potential for effectively treating biofilm-associated infections, addressing the urgent need for strategies to combat antibiotic-resistant biofilms, particularly mixed-species biofilm, in medical settings.
生物膜,尤其是由多种细菌形成的生物膜,给经济和环境带来了巨大的挑战,特别是在医学植入物方面。为了解决对抗生素耐药性加剧的有效治疗策略的迫切需求,我们开发了一种基于黑磷纳米片(BPN)的新型纳米制剂 Ce6&PMb@BPN,用于靶向治疗由鲍曼不动杆菌(A.baumannii)和耐甲氧西林金黄色葡萄球菌(MRSA)形成的混合物种生物膜。该制剂利用多粘菌素 B(PMb)进行细菌靶向,利用氯乙酮(Ce6)进行光动力作用。在近红外(NIR)照射下,Ce6&PMb@BPN 通过化学疗法、光动力疗法(PDT)和光热疗法(PTT)的联合作用,有效地消除生物膜,在 30 分钟内显著减少生物膜生物量。在感染混合物种生物膜涂层导管的小鼠体内研究中,该制剂表现出强大的抗菌和生物膜消融作用。此外,全面的生物安全评估证实了 Ce6&PMb@BPN 的优异生物相容性。总之,这种智能设计的纳米制剂具有有效治疗生物膜相关感染的潜力,满足了在医疗环境中对抗抗生素耐药性生物膜(特别是混合物种生物膜)的策略的迫切需求。