| Nanomedicine has been developing rapidly in the treatment of tumor in recent years.The nanomedicine delivery system can effectively improve the bioavailability of the drug,reduce the dose and reduce the side effects of the drug by changing the distribution of the drug and releasing the drug in the tumor microenvironment.In this research,natural inorganic materials-halloysite nanotubes（HNTs）were functionalized with folate-targeted molecules（FA）and hyaluronic acid-targeted molecules（HA）respectively.The antitumor activities were preliminarily studied,the details are as follows:（1）Size adjustment of Halloysite nanotubes:Halloysite nanotubes have been used widely in biomedicine for their excellent biocompatibility,hydrophilicity and chemical stability.But HNTs are not uniform in sizes,and larger nanotubes can damage cells and cause inflammation.We adjusted the HNTs size via ultrasound and centrifugation for cell endocytosis.（2）In this work,polyglycerol（PG）is modified with HNTs-PG via esterification reaction to produce tumor targeting nanocomposite（HNTs-PG-FA）.Thereafter,doxorubicin（DOX）was loaded on novel targeted anticancer delivery system HNTs-PG-FA,which can bind specifically to tumor cells with overexpressed the folate receptor.The obtained nanomaterials were fully characterized using FT-IR,TEM,XPS,TGA and DLS techniques.The results of cytotoxicity showed that HNTs-PG-FA has good stability,low cytotoxicity and side effect to cells.HNTs-PG-FA/DOX has more significant inhibition than free DOX.The results of Flow cytometry showed that HNTs-PG-FA/DOX could increase the apoptosis rate of He La cells.These results indicate that folate and polyglycerol modified halloysite nanotubes can be used as anti-tumor targeting delivery system carriers,with broad prospects in cancer treatment.（3）The antitumor drug delivery system possesses low targeting ability and low efficiency for disease sites,limiting practical clinical applications.CD44,an adhesion/homing molecule,overexpressed in aggressive cancer cells,was a major receptor for hyaluronic acid（HA）.In this study,a novel halloysite（HNTs）nanotube-based carrier,was designed for an efficient CD44-targeted antitumor drug delivery.The successful synthesis of hyaluronic acid grafted HNTs（HNTs-NH-HA）complexes were proved by 13C solid state NMR spectroscopy,FT-IR,XPS and TGA.A model anticancer drug doxorubicin（DOX）was loaded into HNTs-NH-HA delivery nanocarrier（HNTs-NH-HA/DOX）.In vitro cytotoxicity analysis showed that HNTs-NH-HA were effective in targeted delivery and enhanced the therapeutic efficacy of the DOX.Furthermore,confocal laser scanning microscopy（CLSM）demonstrated that the HNTs-NH-HA/DOX nanoparticles exhibited much better cellular uptake in He La（CD44receptor-positive）cells than in Hep G2（CD44 receptor-negative）cells.It was expected that HNTs-NH-HA drug delivery systems hold a great potential for targeting CD44 over-expressing tumors. |
