Multifunctional Hydrogel Research For The Prevention Of Pancreatic Fistula And Residual Tumor Recurrence After Pancreatic Cancer Surgery

BackgroundPancreatic cancer is a highly malignant digestive tract tumor with a five-year survival rate of less than 10%.Although surgery is considered the only treatment that can cure pancreatic cancer,patients are at risk of pancreatic fistula and tumor recurrence after surgery.The main causes of these complications include:the pancreas has a rich pancreatic duct system,and it is difficult to seal all the pancreatic ducts after surgery,resulting in postoperative pancreatic fistula.On the other hand,residual microtumor and circulating tumor cells after pancreatic cancer resection lead to high postoperative recurrence and metastasis rates.In recent years,hydrogel,as an emerging biological material,can be used to prevent postoperative complications and serve as a good drug carrier to load drugs for treatment.However,there are no hydrogels for pancreatic fistula and tumor recurrence after pancreatic cancer surgery.Based on the above clinical problems,this study designed the structure of hydrogel and included immunotherapy drugs to prevent pancreatic fistula and tumor recurrence after pancreatic cancer surgery.ObjectiveThe purpose of this study was to design and construct(P-aTIGIT&PDA@IL-15)@gel for postoperative pancreatic cancer,which can seal the broken end of the pancreas and absorb the leaking pancreatic fluid.In addition,aTIGIT and IL-15 are slowly released to activate CD8+T cells and NK cells in vivo,thus playing a role in preventing pancreatic fistula and inhibiting postoperative tumor recurrence.MethodsIn this study,hyaluronic acid was modified to construct a double-crosslinked and drug-loaded(P-aTIGIT&PDA@IL-15)@gel.The characterization of the hydrogel was verified by electron microscopy,nuclear magnetic hydrogen spectrum analysis and fluid strain gauge analysis.The safety of the hydrogel was verified by CCK-8,erythrocyte hemolysis test and AM/PI staining.A rat pancreatic fistula model was established to verify the preventive effect of hydrogel on pancreatic fistula,a pancreatic cancer incomplete resection model was constructed to verify the inhibitory effect of hydrogel on residual tumor recurrence,and a subcutaneous tumor distant metastasis model and a pancreatic cancer liver metastasis model were constructed to verify the inhibitory effect of hydrogel on distant metastatic tumor focus.ResultsIn this study,we constructed(P-aTIGIT&PDA@IL-15)@gel and verified its good biosafety and tissue adhesion.We have verified in vitro that the hydrogel has good stability and does not cause leakage of the contained fluorescent material.Meanwhile,the hydrogel can be maintained in rats for more than 28 days and degrade slowly.After pancreatic cancer resection,the hydrogel can adhere very well to the stump of the pancreas to seal the severed end of the pancreas and effectively prevent the increase of amylase and lipase levels in the abdominal cavity after surgery.At the same time,it can increase CD8+T cell infiltration by 6 times and NK1.1+ cell infiltration by 1 times in postoperative residual tumor,effectively inhibit the growth of residual tumor after pancreatic cancer resection,and prolong the survival of mice.ConclusionIn this study,we constructed(P-aTIGIT&PDA@IL-15)@gel to treat postoperative complications of pancreatic cancer.The results showed that the hydrogel could effectively prevent pancreatic fistula after pancreatic cancer surgery and inhibit the recurrence of residual tumors,providing a new treatment strategy for preventing and alleviating postoperative complications of pancreatic cancer and inhibiting tumor recurrence.