title: Double-layered hyaluronic acid/stearic acid-modified polyethyleneimine nanoparticles encapsulating (-)-gossypol: a nanocarrier for chiral anticancer drugs.
abstract: This study aimed to enhance the water solubility and antitumor efficacy of (-)-gossypol. Polyethyleneimine conjugated with stearic acid (PgS) was used for loading and protecting (-)-gossypol through hydrogen bonding. Double-layered hyaluronic acid (HA)-modified PgS nanoparticles encapsulating (-)-gossypol [(-)-G-PgSHAs] were prepared through a two-step fabrication process. The nanoparticles possessed a uniform spherical shape with a dynamic size of 110.9 ± 2.4 nm, which was determined through transmission electron microscopy and dynamic light scattering analysis. The encapsulation efficiency and drug-loading capacity of (-)-G-PgSHAs were 72.6% ± 3.1% and 9.1% ± 0.42%, respectively. The IR spectra of the samples confirmed the protection effect of hydrogen bonding on the optical activity of the encapsulated (-)-gossypol. (-)-G-PgSHAs exhibited a controlled and tumor-specific release because of the high expression of HAase in the tumor region. The tumor-targeting feature of PgSHAs due to HA-receptor mediation was confirmed byin vitrocell uptake andin vivonear infrared fluorescence imaging. Thein vitrotest showed that the (-)-G-PgSHAs had similar cytotoxicity to free (-)-gossypol and was smaller than that of the encapsulated (±)-gossypol [(±)-G-PgSHAs]. Thein vivostudy of the anti-cancer effect of (-)-G-PgSHAs revealed that (-)-G-PgSHAs had a more enhanced tumor-suppression effect and reduced systemic toxicity compared with free (-)-gossypol and (±)-G-PgSHAs (P< 0.05). Therefore, PgSHA was a useful (-)-gossypol nanocarrier that exhibits high biocompatibility, tunable release of drug, and tumor-targeting characteristics for cancer treatment. In addition, this double-layered nanocarrier provided novel strategies for the encapsulation of other chiral drugs.
authors.affiliation: Key Laboratory of Biomedical Information Engineering of Education Ministry, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China. Tel: +86 (029) 82663941; Department of Molecular Biosciences, The University of Kansas, Lawrence, Kansas, USA. Tel: +1 (785) 864 6319.
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, China. Tel: +86 (029) 82663941.
authors.forename: Ke
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Molecular Biosciences, The University of Kansas, Lawrence, Kansas, USA. Tel: +1 (785) 864 6319.
authors.forename: Lan
authors.initials: L
authors.lastname: Lan
authors.affiliation: Key Laboratory of Biomedical Information Engineering of Education Ministry, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China. Tel: +86 (029) 82663941.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Ma
authors.affiliation: Key Laboratory of Biomedical Information Engineering of Education Ministry, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China. Tel: +86 (029) 82663941.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Department of Molecular Biosciences, The University of Kansas, Lawrence, Kansas, USA. Tel: +1 (785) 864 6319; Department of Radiation Oncology, The University of Kansas Cancer Center, Kansas City, Kansas, 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, China. Tel: +86 (029) 82663941.
authors.forename: Daocheng
authors.initials: D
authors.lastname: Wu