PH-responsive nanocomposite hydrogel for simultaneous prevention of postoperative adhesion and tumor recurrence.

Abstract

Abdominal adhesion and tumor recurrence are two thorny problems in the postoperative treatment of abdominal tumors. Although important progress has been made in the application of hydrogels in adjuvant therapy after tumor surgery, most of the products can not effectively combine the prevention of abdominal adhesion and the removal of residual cancer cells. In this study, a nanocomposite hydrogel (Col-APG-Cys@HHD) was prepared by crosslinking collagen and recombinant albumin nanoparticles (HHD NPs) with aldehydeylated polyethylene glycol (APG6K) followed by immobilizing zwitterionic cysteine (Cys) to one surface. One surface of the hydrogel adhered to the postoperative wound due to the adhesive properties of collagen, while the other surface coated with cysteine formed a hydration layer to hinder the stick of proteins and cells, thereby reducing the adhesion between tissues. Additionally, Col-APG-Cys@HHD hydrogel disintegrated under acidic condition and released HHD NPs that targeted into cancer cells and released drugs in response to low pH environment. The in vivo experiments' results demonstrated that Col-APG-Cys@HHD hydrogel could prevent intraperitoneal adhesions and inhibit tumor growth with minimal side effects, providing a potential strategy for the hydrogel-based drug delivery system in postoperative adjuvant therapy of tumors. STATEMENT OF SIGNIFICANCE: Tissue adhesion and tumor recurrence usually occur after abdominal tumor surgery. Hydrogels have been widely studied in adjuvant treatment of abdominal tumors, but their synergy in terms of controllable drug release and anti-peritoneal adhesion still needs to be improved. Herein, a nanocomposite hydrogel (Col-APG-Cys@HHD) was designed and constructed with one side that was tissue adhesive and the other side as antifouling. Additionally, the Col-APG-Cys@HHD hydrogel showed controlled drug release behavior in response to a pH gradient (6.5 to 5.5). This was conducive to its dissociation in an acidic tumor environment followed by the release of nanoparticles that entered into tumor cells and delivered docetaxel . To sum up, the Col-APG-Cys@HHD hydrogel demonstrated synergistic therapy for prevention of abdominal adhesion and tumor recurrence after abdominal tumor surgery.