An Integrated Strategy for Rapid Hemostasis during Tumor Resection and Prevention of Postoperative Tumor Recurrence of Hepatocellular Carcinoma by Antibacterial Shape Memory Cryogel.

Abstract

The inevitable bleeding during tumor resection greatly increases the risk of tumor recurrence caused by metastasis of cancer cells with blood, and hemostasis and prevention of post-operation tumor recurrence is still a challenge. However, a biomaterials approach for rapid hemostasis during tumor resection and simultaneous prevention of tumor recurrence is rarely reported. Here, zeolitic imidazolate framework (ZIF-8) nanoparticle-enhanced multinetwork cryogels are proposed which provide an integrated treatment regimen for rapid hemostasis through intraoperative blood trigger shape recovery and enhanced coagulation, and prevention of postoperative cancer recurrence via sonodynamic anticancer in a hepatocellular carcinoma model. A series of antibacterial shape memory multifunctional cryogels are synthesized based on glycidyl methacrylate-functionalized quaternized chitosan (QCSG), dopamine-modified hyaluronic acid (HA-DA), and hematoporphyrin monomethyl ether (HMME)-loaded dopamine-modified ZIF-8 (ZDH). Blood loss in different bleeding models confirms good hemostasis of ZIF-8 loading cryogels. Besides, in vitro tests confirm that QCSG/HA-DA/ZDH (QH/ZDH) cryogels significantly killed cancer cells by generating reactive oxygen species under ultrasound. Finally, significantly reduced tumor recurrence after the resection of ectopic hepatocellular carcinoma further confirms the good effect of QH/ZDH cryogels in preventing recurrence by a coordinated strategy of intraoperative hemostasis and postoperative sonodynamic therapy by pH-responsive HMME release, showing great potential in clinical application.