title: Bacillus-shape design of polymer based drug delivery systems with janus-faced function for synergistic targeted drug delivery and more effective cancer therapy.
abstract: The particle shape of the drug delivery systems had a strong impact on their in vitro and in vivo performance, but there was limited availability of techniques to produce the specific shaped drug carriers. In this article, the novel methotrexate (MTX) decorated MPEG-PLA nanobacillus (MPEG-PLA-MTX NB) was prepared by the self-assembly technique followed by the extrusion through SPG membrane with high N2 pressure for targeted drug delivery, in which Janus-like MTX was not only used as a specific anticancer drug but could also be served as a tumor-targeting ligand. The MPEG-PLA-MTX NBs demonstrated much higher in vitro and in vivo targeting efficiency compared to the MPEG-PLA-MTX nanospheres (MPEG-PLA-MTX NSs) and MPEG-PLA nanospheres (MPEG-PLA NSs). In addition, the MPEG-PLA-MTX NBs also displayed much more excellent in vitro and in vivo antitumor activity than the MPEG-PLA-MTX NSs and free MTX injection. To our knowledge, this work provided the first example of the integration of the shape design (which mediated an early phase tumor accumulation and a late-phase cell internalization) and Janus-faced function (which mediated an early phase active targeting effect and a late-phase anticancer effect) on the basis of nanoscaled drug delivery systems. The highly convergent and cooperative drug delivery strategy opens the door to more drug delivery systems with new shapes and functions for cancer therapy.
authors.affiliation: †Department of Biomaterials, Research Center of Biomedical Engineering, Institute of Soft Matter and Biomimetics, College of Materials, Xiamen University, Xiamen 361005, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Cui
authors.affiliation: †Department of Biomaterials, Research Center of Biomedical Engineering, Institute of Soft Matter and Biomimetics, College of Materials, Xiamen University, Xiamen 361005, China.|§Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.|#Department of Materials Science and Engineering, College of Materials, Xiamen University, Xiamen 361005, China.
authors.forename: Jinyan
authors.initials: J
authors.lastname: Lin
authors.affiliation: †Department of Biomaterials, Research Center of Biomedical Engineering, Institute of Soft Matter and Biomimetics, College of Materials, Xiamen University, Xiamen 361005, China.|§Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.|#Department of Materials Science and Engineering, College of Materials, Xiamen University, Xiamen 361005, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: †Department of Biomaterials, Research Center of Biomedical Engineering, Institute of Soft Matter and Biomimetics, College of Materials, Xiamen University, Xiamen 361005, China.
authors.forename: Yanxiu
authors.initials: Y
authors.lastname: Li
authors.affiliation: ‡Department of Pharmacy, School of Pharmaceutical Science, Xiamen University, Xiamen 361102, China.
authors.forename: Hongjie
authors.initials: H
authors.lastname: Wu
authors.affiliation: §Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yu
authors.affiliation: †Department of Biomaterials, Research Center of Biomedical Engineering, Institute of Soft Matter and Biomimetics, College of Materials, Xiamen University, Xiamen 361005, China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Jia
authors.affiliation: †Department of Biomaterials, Research Center of Biomedical Engineering, Institute of Soft Matter and Biomimetics, College of Materials, Xiamen University, Xiamen 361005, China.|#Department of Materials Science and Engineering, College of Materials, Xiamen University, Xiamen 361005, China.
authors.forename: Xiangrui
authors.initials: X
authors.lastname: Yang
authors.affiliation: †Department of Biomaterials, Research Center of Biomedical Engineering, Institute of Soft Matter and Biomimetics, College of Materials, Xiamen University, Xiamen 361005, China.|§Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.
authors.forename: Shichao
authors.initials: S
authors.lastname: Wu
authors.affiliation: ⊥The First Affiliated Hospital of Xiamen University, Xiamen 361002, China.
authors.forename: Liya
authors.initials: L
authors.lastname: Xie
authors.affiliation: †Department of Biomaterials, Research Center of Biomedical Engineering, Institute of Soft Matter and Biomimetics, College of Materials, Xiamen University, Xiamen 361005, China.
authors.forename: Shefang
authors.initials: S
authors.lastname: Ye
authors.affiliation: ∥Cancer Research Center, Medical College, Xiamen University, Xiamen 361005, China.
authors.forename: Fanghong
authors.initials: F
authors.lastname: Luo
authors.affiliation: †Department of Biomaterials, Research Center of Biomedical Engineering, Institute of Soft Matter and Biomimetics, College of Materials, Xiamen University, Xiamen 361005, China.
authors.forename: Zhenqing
authors.initials: Z
authors.lastname: Hou
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D001407:Bacillus; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D008727:Methotrexate / Q000008:administration & dosage; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy*; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D011091:Polyesters; D011108:Polymers; C492425:methoxy poly(ethylene glycol)-poly(lactide); D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide); D008727:Methotrexate
keywords: MPEG-PLA; anticancer; drug vehicle; methotrexate; targeting