Controllable Design Of Silk Based Carriers For Drug Controlled Release And Their Application In Cancer Treatment

Cancer is a complex disease with high mortality and dramatically increased cases.New strategies are necessary for cancer treatment to effectively improve the bioavailability of chemical drugs,reduce toxic side effects and improve the effect of cancer treatment.Basically,passive targeting,active targeting and localized chemotherapy are developing to enrichment drug in tumor and promote the effective release of drugs in the lesion site.Though several improvements have been achieved,a huge challenge remains to design a carrier with mild and simple process,biocompatibility,biodegradability,low immunogenicity,and effective loading and releasing of drugs.Silk,a natural derived protein,is a generic drug carrier for controlled release system with impressive biocompatibility,low immunogenicity,by-product nontoxicity,pH sensitivity,drug stabilization and tunable drug release capacity.Here,combining practicall needs of cancer treatment and superiority of silk as carriers,we developed several silk based carriers based on basical strategies of designing drug release system to achieve better performances for cancer treatment.By controlling the degree of silk protein dissolution,silk nanoparticles were formed directly without relative complex process.The nanoparticles have suitable stability in water and culture media and improved cellular uptake.As carriers,the silk nanoparticles showed a pH stimulating capacity and better antitumor properties.The results indicated that the silk nanoparticle as carriers for drug controlled release system was beneficial.Then,thixotropic silk nanofiber hydrogel as carriers for drug controlled release was discussed to assess its application in localized chemotherapy.The silk nanofiber hydrogels were formed through self assembly in aqueous solution.Injectable DOX loaded silk nanofiber hydrogels were applied to the breast cancer model for localized chemotherapy.The system can be injected and rapidly solidify after injection,with pH stimulating response and silk content dependent release behavior.In vitro and in vivo studies showed that DOX loaded silk nanofiber hydrogels were suitable injecatble carriers for cancer treatment.Finally,we highlighted the problems of poor water solubility and low bioavailability of hydrophobic drugs.We discussed the feasibility of hydrophobic and water dispersible silk nanofiber as carriers transferring hydrophobic material from organic solvent to aqueous solution.This study provided useful information for subsequent use of the silk nanofibers to load hydrophobic drugs in aqueous solution and also co-loading of multiple drugs.Therefore,we developed several novel silk-based carriers to satisfy various requirements of cancer treatment.Better performances were achieved for these carriers,suggesting their promising future in clinical applications.