Phenylboronic acid functionalized dextran loading curcumin as nano-therapeutics for promoting the bacteria-infected diabetic wound healing

Chronic bacterial infections, excessive inflammation, and oxidative stress significantly hinder diabetic wound healing by prolonging the inflammatory phase and complicating the healing process. In this study, phenylboronic acid functionalized dextran (PODP) was developed to encapsulate curcumin, referred to as PODP@Cur. Experimental results indicate that PODP significantly improves the water solubility of curcumin and exhibits synergistic biological activity both in vitro and in vivo. PODP@Cur is capable of accelerating drug release under the pathological microenvironment with ROS accumulation. Furthermore, phenylboronic acid (PBA) has demonstrated potential for targeted bacterial drug delivery, enhancing antibacterial efficacy and trapping free LPS/PGN from dead bacteria to reduce undesirable inflammation. In a diabetic mouse model, PODP@Cur exhibits an excellent antibacterial, anti-inflammatory and antioxidant activities to ultimately promote the efficient and safe wound healing. Due to the specific interaction between PBA and LPS, PODP@Cur could enhance antibacterial activity against bacteria, reduce toxic side effects on normal cells, and alleviate the LPS-mediated pro-inflammatory pathological microenvironment. Therefore, PODP@Cur is capable of being exploited as an efficient and safe candidate for promoting the bacteria-infected diabetic wound healing.