Liver Targeting Of Surface Modified Calcium Carbonate Hollow Nanospheres

Objectives In a proper way,the functions of p H sensitivity,receptor targeting and synergistic drug delivery are integrated into a carrier,which will become an "All-in-one" multi-functional drug delivery system,and will play its intelligent advantages in the treatment of cancer.In this context,focusing on the application of drug carriers for liver cancer,the surface modified calcium carbonate hollow nanospheres are prepared in order to achieve the controlled release of nanospheres in cancer environment and achieve receptor targeting for cancer cells.Methods There were three steps to synthesize the composite carriers.1.Preparation of Calcium carbonate hollow nanospheres(CCNSs).CCNSs were prepared by using water soluble polymer PVP and SDS as organic templates.2.The preliminary synthesis of targeted modifiers.Chitosan(CS)and lactose acid(LA)were grafted to generate the product LA-CS under the catalysis of EDC / NHS.3.Preparation of composite nanospheres.Using "one-pot method",under the protection of nitrogen,along with MMA was added,the copolymer(LA-CS-PMMA)was formed under the catalysis of potassium persulfate,and then LA-CS-PMMA adsorbed on the surface of CCNSs.Doxorubicin hydrochloride(DOX)was selected as the model drug to determine the drug loading,entrapment efficiency,stability,cytotoxicity and distribution in mice.Results 1.Calcium carbonate hollow nanospheres(CCNSs)were successfully prepared.Transmission electron microscopy showed that CCNSs were spherical,with an average particle size of about 250 nm,mesoporous and large cavities.2.The surface modifiers with grafting ratio of 12.4%,26.9% and 43.5% were prepared respectively.3.The particle size of CCNSs modified by LA-CS-PMMA increased significantly.The particle size analysis showed that the average particle size of CCNSs after modification increased by 80 nm,and the Zeta potential increased from-20.8 m V to-48.5 m V.MTT test showed that LA-CSPMMA-CCNSs had good biocompatibility,and DOX@LA-CS-PMMA-CCNSs can rapidly reduce the cell survival rate.BCA method proved that LA-CS-PMMA-CCNSs had obvious Hep G2 cell targeting.The results of animal experiments showed that DOX@LA-CSPMMA-CCNSs had the highest DOX content in the liver of mice after intravenous injection of DOX@LA-CS-PMMA-CCNSs.Conclusions These results show that the core-shell carrier of calcium carbonate has good biosafety,sensitive p H responsibility and liver targeting,with a promising application prospect as a cancer targeting carrier.Figure 18;Table 18;Reference 106...