Chi@HMPB@CBD nanocomplexes for laser-assisted therapy of MRSA-infected cutaneous wounds in normal and MKR diabetic mice

Abstract

The emergence and spreading of methicillin-resistant Staphylococcus aureus (MRSA) have become one of the main reasons for the surgical failure even for the death. Thus, there is an urgent need to develop efficient antimicrobial alternatives for eradicating it so as to improve the therapy efficiency of related diseases. Although the synthesized metal nanoparticles showed the MRSA-killing function in vitro, their biosafety in vivo application is still in controversy due to the potential toxicity and induced multidrug resistance. Recently, plant natural compounds with high antibacterial activity and special mechanisms different from antibiotics have attracted wide interest for developing new anti-MRSA regents. In this work, new nanocomplexes of Chi@HMPB@CBD based on natural compounds of cannabidiol (CBD) and chitosan (Chi) were designed for eradicating MRSA. In vitro results demonstrate that Chi@HMPB@CBD NPs plus laser irradiation can efficiently kill MRSA by inducing bacterial surface perforation, content leakage, ROS production, and ATP reduction. In vivo results show that the combination of Chi@HMPB@CBD NPs plus laser can effectively remove bacteria and accelerate wound healing of MRSA-infected normal and diabetes mellitus mice by up-regulating VEGF and CD31. Moreover, Chi@HMPB@CBD NPs possessing excellent biocompatibility and ultra-low toxicity in vitro significantly delayed the time for multidrug-resistance induction, comparing with silver nanoparticles. In our point, the “green therapeutics” against MRSA show great potential in clinical application.