title: Enhanced anticancer activity of DM1-loaded star-shaped folate-core PLA-TPGS nanoparticles.
abstract: The efficient delivery of therapeutic drugs into interested cells is a critical challenge to broad application of nonviral vector systems. In this research, emtansine (DM1)-loaded star-shaped folate-core polylactide-d-α-tocopheryl polyethylene glycol 1000 succinate (FA-PLA-TPGS-DM1) copolymer which demonstrated superior anticancer activity in vitro/vivo in comparison with linear FA-PLA-TPGS nanoparticles was applied to be a vector of DM1 for FR(+) breast cancer therapy. The DM1- or coumarin 6-loaded nanoparticles were fabricated, and then characterized in terms of size, morphology, drug encapsulation efficiency, and in vitro drug release. And the viability of MCF-7/HER2 cells treated with FA-DM1-nanoparticles (NPs) was assessed. Severe combined immunodeficient mice carrying MCF-7/HER2 tumor xenografts were treated in several groups including phosphate-buffered saline control, DM1, DM1-NPs, and FA-DM1-NPs. The antitumor activity was then assessed by survival time and solid tumor volume. All the specimens were prepared for formalin-fixed and paraffin-embedded tissue sections for hematoxylin-eosin staining. The data showed that the FA-DM1-NPs could efficiently deliver DM1 into MCF-7/HER2 cells. The cytotoxicity of DM1 to MCF-7/HER2 cells was significantly increased by FA-DM1-NPs when compared with the control groups. In conclusion, the FA-DM1-NPs offered a considerable potential formulation for FR(+) tumor-targeting biotherapy.
authors.affiliation: Stem cell Engineering Research Center, School of Medical, Anhui University of Science & Technology, Huainan 232001, China ; The State Key Laboratory of Virology, Life Sciences College, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Tang
authors.affiliation: Clinical Laboratory, The Affiliated Huai'an Hospital of Xuzhou Medical College, Huai'an 223002, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Medical Genetics, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Stem cell Engineering Research Center, School of Medical, Anhui University of Science & Technology, Huainan 232001, China.
authors.forename: Shiyu
authors.initials: S
authors.lastname: Cai
authors.affiliation: Northeastern University, Boston, MA 02115, USA.
authors.forename: Leilei
authors.initials: L
authors.lastname: Sun
authors.affiliation: Stem cell Engineering Research Center, School of Medical, Anhui University of Science & Technology, Huainan 232001, China.
authors.forename: Tianyi
authors.initials: T
authors.lastname: Chen
keywords: Drug delivery; Emtansine (DM1); Targeting nanoparticles