title: Mulberry-like dual-drug complicated nanocarriers assembled with apogossypolone amphiphilic starch micelles and doxorubicin hyaluronic acid nanoparticles for tumor combination and targeted therapy.
abstract: A comprehensive strategy for the preparation of mulberry-like dual-drug complicated nanocarriers (MLDC NCs) with high drug loading and adjustable dual-drug ratio was developed. First, apogossypolone (ApoG2) amphiphilic starch micelles (AASt MCs) were prepared by self-assembly process, and doxorubicin (DOX) hyaluronic acid nanoparticles (DHA NPs) were prepared by DOX absorption with excess HA by electrostatic absorption. MLDC NCs were obtained by adsorption of 8-9 DHA NPs around one AASt MC via electrostatic interaction. UV-visible and fluorescence spectrophotometers were used to measure the entrapment efficiency and loading efficiency of the two drugs. Transmission electron microscope and dynamic light scattering method were used to observe the size distribution and morphology of the particles. The tumor-targeting feature caused by HA-receptor mediation was confirmed by in vitro cell uptake and in vivo near-infrared fluorescence imaging. MLDC NCs were found to possess a mulberry-like shape with a dynamic size of 83.1 ± 6.6 nm. The final encapsulation efficiencies of ApoG2 and DOX in MLDC NCs were 94 ± 1.7% and 87 ± 5.8% with respect to drug-loading capacities of 13.3 ± 1.2% and 13.1 ± 3.7%, respectively. Almost no ApoG2 release was found within 80 h and less than 30% of DOX was released into the outer phase even after 72 h. In vivo fluorescence imaging revealed that MLDC NCs had highly efficient targeting and accumulation at the tumor in vivo and was maintained for 96 h after being injected intravenously in mice. Low LD50 for the two drugs in MLDC NCs was found after acute toxicity test. One-fifth normal dosage of the two drugs in MLDC NCs exhibited significantly higher anti-tumor efficiency in reducing tumor size compared with free drugs combination or single drug-loaded nanoparticles individually, indicating that the mulberry-like dual-drug nanoplatform has a great potential in tumor therapy.
authors.affiliation: Key Laboratory of Biomedical Information Engineering of Education Ministry, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Li
authors.affiliation: Key Laboratory of Biomedical Information Engineering of Education Ministry, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Key Laboratory of Biomedical Information Engineering of Education Ministry, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.affiliation: Key Laboratory of Biomedical Information Engineering of Education Ministry, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
authors.forename: Mu
authors.initials: M
authors.lastname: Chen
authors.affiliation: Key Laboratory of Biomedical Information Engineering of Education Ministry, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Biomedical Information Engineering of Education Ministry, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Molecular Biosciences, Department of Urology and Radiation Oncology, University of Kansas Cancer Center, University of Kansas, Lawrence, KS, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Xu
authors.affiliation: Key Laboratory of Biomedical Information Engineering of Education Ministry, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China. Electronic address: wudaocheng@mail.xjtu.edu.cn.
authors.forename: Daocheng
authors.initials: D
authors.lastname: Wu
mesh_terms: D000818:Animals; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D006072:Gossypol / Q000031:analogs & derivatives* / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D031625:Morus; D053758:Nanoparticles / Q000737:chemistry*; D013213:Starch / Q000737:chemistry*
chemical_list: D008823:Micelles; C534401:apogossypolone; D004317:Doxorubicin; D006820:Hyaluronic Acid; D013213:Starch; D006072:Gossypol
keywords: Apogossypolone; Chemotherapy; Combination therapy; Doxorubicin; Mulberry-like dual-drug complicated nanocarriers