Polydopamine Surface-modified Hyperbranched Polymeric Nanoparticles For The Chemo/photothermal Synergistic Therapy Of Oral Cancer

Background:The incidence of oral cancer has been increasing,and its prognosis is poor.Patients often suffer from postoperative complications such as facial deformities,dysarthria and loss of taste.Traditional treatment modalities,including surgery,radiotherapy and chemotherapy,have certain drawbacks.Radiotherapy and chemotherapy don’t target diseased cells,resulting in serious damage to normal tissues.With the development of nanomedicine,the use of nanotechnology in the treatment of malignant tumors has been increasingly researched.Polymeric nano-drug carriers can reduce drug toxicity and improve drug efficacy by improving drug encapsulation,prolonging circulating half-life,controlling drug release and targeting drug delivery to tumor tissue.Photothermal therapy is a non-invasive technique for the treatment of cancer.It kills tumor cells by generating localized high temperatures in specific areas and is highly effective in killing superficial localized solid tumors,and a large proportion of oral cancers are manifested in exposed areas of the mouth.Polydopamine is used for surface modification of polymeric nanoparticles,which is beneficial for improving the stability of polymeric nanoparticles in vivo,combined with hydrophilic groups such as PEG,with high NIR photothermal conversion efficiency.Based on the above,the use of surface modification of polydopamine-loaded chemotherapeutic drug-polymer nanoparticles is expected to develop a nanoplatform capable of synergistic chemotherapy and photothermal treatment of oral cancer.Objective:Developing novel nanoplatforms capable of synergistic chemotherapy and photothermal treatment of oral cancer through investigating the characterization,photothermal properties,in vitro drug release,cellular uptake,and cytotoxicity of drug-loaded nanoparticles（DOX/H20-PLA@PDA-PEG-FA NPs）.Methods:The drug-loaded nanoparticles（DOX/H20-PLA@PDA-PEG-FA NPs）in this experiment were prepared according to the following steps:loading of DOX,surface modification with polydopamine,and attachment of the targeting ligand（H₂N-PEG-FA）.The characterization of the NPs was studied by TEM,DLS and XPS.The photothermal properties of the NPs were evaluated,and the drug release profiles in vitro were plotted by HPLC.Conducting in vitro cellular experiments,which include cellular uptake of the NPs and cytotoxicity assays.Results:The diameter size of the drug-loaded nanoparticles facilitates entry into tumor cells and the negative surface potential facilitates prolonged in vivo circulation before enrichment at the tumor tissue.Their surface-modified PDA coating and attached targeting ligands together facilitate the enrichment of nanoparticles in tumor tissue.And that increasing drug release in the acidic tumor microenvironment under laser irradiation due to their photothermal properties and the p H sensitivity of the PDA coating.The results of cellular experiments show that the drug-free NPs display non-cytotoxicity and high biocompatibility.Conclusion:DOX/H20-PLA@PDA-PEG-FA NPs have strong photothermal conversion and targeted drug delivery capabilities,which provide a new idea for the clinical treatment of oral cancer.