Synthesis And Biological Application Of Grapheneoxide Nanosheets Based Thermosensitive Polymer Hydrogels

Gels are intermediate state of matter between solid and liquid states and is an important class of soft matter.It contains three dimensional fibrillar percolation network structure and in between a large amount of solvent remains trapped.Gels are usually made of hydrophilic polymer or polymer by covalent bond,hydrogen bond and van der Waals force.Hydrogels can be classified into natural polymer hydrogels and synthetic polymer hydrogels.The nature hydrogels are synthesized by using nature polymer,such as collagen,gelatin,fibrin,chitosan,sodium alginate,hyaluronic acid,chondroitin sulfate,agarose and other natural polymer materials.Synthetic polymer hydrogels mainly consist of polyethylene glycol,polyvinyl alcohol,poly hydroxyethyl methacrylate,polyacrylamide,polyacrylic acid and its derivatives.However,the pure polymer hydrogel still has shortcomings such as insufficient mechanical properties and single function.In recent years,smart responsive hydrogels,including thermo responsive,have attract more and more attention.Hydrogels with substantially improved mechanical properties have been achieved by engineering their interfaces and nanostructures.Most hydrogels are porous,which provides a high surface area that facilitates strong interaction between the fillers and the substrates.On the basis of ABA block polymer thermosensitive hydrogel,this study developed two bio-hydrogels with multi-functions,such as antibacterial,promotes wound healing,anti-tumor recurrence,hemostasis ability,and TAE,including the following parts:(1): An in situ forming hydrogel has emerged as a promising wound dressing recently.As physically crosslinked hydrogels are normally unstable,most in situ forming hydrogels are chemically cross-linked.However,big concerns have remained regarding the slow gelation and the potential toxicity of residual functional groups from crosslinkers or the polymer matrix.Herein,we report a sprayable in situ forming hydrogel composed of PEP(PNIPAM-co-Pn BA-PEG-Pn BA-co-PNIPAM)and silvernanoparticles-decorated reduced graphene oxide nanosheets(Ag@r GO,denoted as AG)in response to skin temperature.This thermoresponsive hydrogel exhibits intriguing sol-gel irreversibility at low temperatures for the stable dressing of a wound,which is attributed to the inorganic/polymeric dual network and abundant coordination interactions between Ag@r GO nanosheets and PNIPAM.The biocompatibility and antibacterial ability against methicillin-resistant Staphylococcus aureus(MRSA)of this PEP-AG hydrogel wound dressing are confirmed in vitro and in vivo,which could transparently promote the healing of a MRSA-infected skin defect.(2): Despite hepatectomy is the preferred choice to cure HCC,the post-surgical treatment of HCC can not be ignored due to the high incidence of recurrence/metastasis.Especially,intraoperative blood loss and residual tumor at HCC resection margin lead to an increase in both morbidity and mortality.As a non-invasive hyperthermia therapymagnetic hyperthermia therapy(MHT)has been successfully employed in the clinic treatment of numerous malignant tumors including glioblastoma and prostate cancers.In this work,a triblock polymer [Poly(NIPAM-co-DOPA)-PEG-poly(NIPAMco-DOPA)](denoted as NDP)was employed as the thermosensitive polymeric matrix in the response to body temperature,which endows the hydrogel with injectable and in situ gelation properties for post-surgical hemostasis.In addition,as the crucial component in the adhesive protein of marine mussels,dopamine was conjugated to realize effective adhesion of this composite hydrogel on the surgical margin for hepatic cancers.Moreover,to introduce magnetic hyperthermia ability,reduced graphene oxide nanosheets decorated with iron oxide nanoparticles(Fe3O4@r GO,denoted as FG)were incorporated into the hydrogel matrix,which further enhanced the hemostatic ability of this hydrogel via blood coagulation.(3): With the minimal injury to the normal parenchyma,TAE has been regarded as a safe and effective treatment to prolong the survival time of patients with HCC in the advanced stage,which harness the priority blood supply of HCC from the hepatic artery(?95%)to perform local chemotherapy and embolization.The therapeutic effect of TAE on HCC is mainly dependent on the commercial embolization agents including lipiodol and non-absorbable drug-eluting beads(DEBs).However,for super-selected conventional TAE(c TAE),the ultra-fluid lipiodol may cause the ectopic embolism in normal liver tissues after excessive injection and even in the brain and lung.Meanwhile,gelfoam and drug-eluting microspheres with large diameters are difficult to enter into the deep positions surrounding the targeted tumor tissues,which should be failed due to the blood supply from the portal veins and the formation of blood vessel bypass.In consideration of the above limitations of clinically used embolization agents,novel agents with both deep and stable emobilism against HCC are highly required to promote the safety and therapeutic efficacy of TAE,which remains a great challenge.Herein,we have a comprehensive evaluation of the thermosensitive NDP-FG hydrogel as an embolic agent and confirmed that the NDP-FG hydrogel owns the potential for the treatment of hepatocellular carcinoma by transarterial embolization.