title: Multifunctional hyaluronic acid modified graphene oxide loaded with mitoxantrone for overcoming drug resistance in cancer.
abstract: Multifunctional nanosheets (HA-GO/Pluronic) with targeted chemo-photothermal properties were successfully developed for controlled delivery of mitoxantrone (MIT) to overcome multidrug resistance (MDR). In vitro release profiles displayed that both an acidic environment and a NIR laser could trigger and accelerate the release of a drug, which ensured nanosheets were stable in blood circulation and released MIT within tumor cells under laser irradiation. HA-GO/Pluronic nanosheets were taken up into MCF-7/ADR cells via receptor-mediated endocytosis, which further facilitated escapement of P-gp efflux. Compared with MIT solution, MIT/HA-GO/Pluronic showed greater cytotoxicity and increase in cellular MIT accumulation in MCF-7/ADR cells. Cell apoptosis and cell cycle arrest studies also revealed that MIT/HA-GO/Pluronic was more potent than MIT/GO/Pluronic and MIT solution. The anticancer efficacy in vivo was evaluated in MCF-7 and MCF-7/ADR-bearing mice, and inhibition of tumors by MIT/HA-GO/Pluronic with NIR laser irradiation was the most effective among all MIT formulations. In summary, the MIT/HA-GO/Pluronic system had striking functions such as P-gp reversible inhibitor and anticancer efficacy, and could present a promising platform for drug-resistant cancer treatment.
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University, 100 Science Road, Zhengzhou 450001, and Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Hou
authors.forename: Qianhua
authors.initials: Q
authors.lastname: Feng
authors.forename: Yating
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Yang
authors.forename: Junxiao
authors.initials: J
authors.lastname: Ren
authors.forename: Yuyang
authors.initials: Y
authors.lastname: Shi
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Shan
authors.forename: Yujie
authors.initials: Y
authors.lastname: Yuan
authors.forename: Yongchao
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhenzhong
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001940:Breast / Q000187:drug effects / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003692:Delayed-Action Preparations / Q000737:chemistry*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006108:Graphite / Q000737:chemistry*; D006801:Humans; D006820:Hyaluronic Acid / Q000031:analogs & derivatives*; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008942:Mitoxantrone / Q000008:administration & dosage* / Q000627:therapeutic use; D049329:Nanostructures / Q000737:chemistry; D010087:Oxides / Q000737:chemistry
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D010087:Oxides; D006108:Graphite; D006820:Hyaluronic Acid; D008942:Mitoxantrone