title: Enhancing Doxorubicin Delivery toward Tumor by Hydroxyethyl Starch-g-Polylactide Partner Nanocarriers.
abstract: Doxorubicin (DOX), a kind of wide-spectrum chemotherapeutic drug, can cause severe side effects in clinical use. To enhance its antitumor efficacy while reducing the side effects, two kinds of nanoparticles with desirable compositions and properties were assembled using optimally synthesized hydroxyethyl starch-grafted-polylactide (HES-g-PLA) copolymers and utilized as partner nanocarriers. The large empty HES-g-PLA nanoparticles (mean size, ca. 700 nm), at an optimized dose of 400 mg/kg, were used to block up the reticuloendothelial system in tumor-bearing mice 1.5 h in advance, and the small DOX-loaded HES-g-PLA nanoparticles (mean size, ca. 130 nm) were subsequently applied to the mice. When these partner nanocarriers were administered in this sequential mode, the released DOX had a significantly prolonged plasma half-life time and much slower clearance rate as well as a largely enhanced intratumoral accumulation as compared to free DOX. In vivo antitumor studies demonstrated that the DOX-loaded HES-g-PLA nanoparticles working together with their partner exhibited remarkably enhanced antitumor efficacy in comparison to free DOX. In addition, these HES-g-PLA partner nanocarriers showed negligible damage to the normal organs of the treated mice. Considering safe and efficient antitumor performance of DOX-loaded HES-g-PLA nanoparticles, the newly developed partner nanocarriers in combination with their administration mode have promising potential in clinical cancer chemotherapy.
authors.affiliation: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology , Wuhan 430074, People's Republic of China.
authors.forename: Chan
authors.initials: C
authors.lastname: Yu
authors.affiliation: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology , Wuhan 430074, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology , Wuhan 430074, People's Republic of China.
authors.forename: Fan
authors.initials: F
authors.lastname: Xiao
authors.affiliation: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology , Wuhan 430074, People's Republic of China.
authors.forename: Yihui
authors.initials: Y
authors.lastname: Li
authors.affiliation: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology , Wuhan 430074, People's Republic of China.
authors.forename: Hang
authors.initials: H
authors.lastname: Hu
authors.affiliation: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology , Wuhan 430074, People's Republic of China.
authors.forename: Ying
authors.identifier: http://orcid.org/0000-0003-1005-5921
authors.initials: Y
authors.lastname: Wan
authors.affiliation: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology , Wuhan 430074, People's Republic of China.|Wuhan Institute of Biotechnology , High Tech Road 666, East Lake High Tech Zone, Wuhan 430040, People's Republic of China.
authors.forename: Zifu
authors.identifier: http://orcid.org/0000-0001-6387-4854
authors.initials: Z
authors.lastname: Li
authors.affiliation: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology , Wuhan 430074, People's Republic of China.
authors.forename: Xiangliang
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004317:Doxorubicin; D004337:Drug Carriers; D016503:Drug Delivery Systems; D051379:Mice; D053758:Nanoparticles; D009369:Neoplasms; D011091:Polyesters; D013213:Starch
chemical_list: D004337:Drug Carriers; D011091:Polyesters; C033616:poly(lactide); D004317:Doxorubicin; D013213:Starch
keywords: cancer chemotherapy; doxorubicin; hydroxyethyl starch copolymer; nanoparticle; partner carrier; polylactide