title: Enhanced Therapeutic Efficacy of Doxorubicin for Breast Cancer Using Chitosan Oligosaccharide-Modified Halloysite Nanotubes.
abstract: Halloysite nanotubes (HNTs) are natural aluminosilicates with unique hollow lumen structure, also having high specific area, good biocompatibility, nontoxicity, and low price. Here, we designed a chitosan oligosaccharide-grafted HNTs (HNTs-g-COS) as a doxorubicin (DOX) carrier for treating breast cancer both in vitro and in vivo. The structure of HNTs-g-COS was first characterized by various methods. HNTs-g-COS showed positively charged surface and improved hemocompatibility. DOX-loaded HNTs-g-COS (DOX@HNTs-g-COS) released in cell lysate in a controlled manner. The IC50value of DOX@HNTs-g-COS toward MCF-7 cells was 1.17 μg mL-1, while it was 2.43 μg mL-1for free DOX. DOX@HNTs-g-COS increased the apoptosis effects of MCF-7 cells as shown in flow cytometry results. Also, reactive oxygen species of cells induced by DOX@HNTs-g-COS were drug-dose-dependent. DOX@HNTs-g-COS could enter the MCF-7 cells and induce mitochondrial damage as well as attack the nuclei. The in vivo antitumor effect of DOX@HNTs-g-COS was investigated in 4T1-bearing mice. The tumor-inhibition ratio of DOX@HNTs-g-COS was 83.5%, while it was 46.1% for free DOX. All mice treated with DOX@HNTs-g-COS survived over 60 days. DOX@HNTs-g-COS showed fewer ruptured cardiomyocytes and no obvious systemic toxicity. Therefore, the rational designed HNTs nanocarrier for chemotherapy drug showed promising applications in tumor treatment.
authors.affiliation: Department of Materials Science and Engineering and ‡College of Pharmacy, Jinan University , Guangzhou 510632, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Materials Science and Engineering and ‡College of Pharmacy, Jinan University , Guangzhou 510632, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Materials Science and Engineering and ‡College of Pharmacy, Jinan University , Guangzhou 510632, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Materials Science and Engineering and ‡College of Pharmacy, Jinan University , Guangzhou 510632, China.
authors.forename: Changren
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Materials Science and Engineering and ‡College of Pharmacy, Jinan University , Guangzhou 510632, China.
authors.forename: Yi-Fang
authors.initials: YF
authors.lastname: Li
authors.affiliation: Department of Materials Science and Engineering and ‡College of Pharmacy, Jinan University , Guangzhou 510632, China.
authors.forename: Rong-Rong
authors.initials: RR
authors.lastname: He
authors.affiliation: Department of Materials Science and Engineering and ‡College of Pharmacy, Jinan University , Guangzhou 510632, China.
authors.forename: Mingxian
authors.initials: M
authors.lastname: Liu
mesh_terms: D000538:Aluminum Silicates; D000818:Animals; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D048271:Chitosan; D000077215:Clay; D004317:Doxorubicin; D006801:Humans; D051379:Mice; D043942:Nanotubes; D009844:Oligosaccharides
chemical_list: D000538:Aluminum Silicates; D009844:Oligosaccharides; D004317:Doxorubicin; D048271:Chitosan; D000077215:Clay
keywords: cell viability; drug delivery; nanotube; surface grafting; tumor therapy