title: Nanoparticle delivery of photosensitive Pt(IV) drugs for circumventing cisplatin cellular pathway and on-demand drug release.
abstract: A photosensitive platinum(IV) prodrug (UVA-Pt2) was attached to a biodegradable polymer (PE, methoxyl-poly(ethylene glycol)-block-poly(lactide-co-2-methyl-2-carboxyl-propylene carbonate-ethanol amine)) and then the conjugate was self-assembled to micelles (NP-UVA-Pt2). In vitro MTT assay of NP-UVA-Pt2 demonstrated an improved cytotoxicity against SKOV-3 cells than that of cisplatin. Confocal laser scanning microscopy (CLSM) indicated that NP-UVA-Pt2 were endocytosed rather than internalized by passive diffusion, and thus, this process has nothing to do with copper transporter protein (Ctr1) as reported for cisplatin, which is closely related to drug resistance of Pt based drugs. Intracellular platinum content measured by ICP-MS result suggested that NP-UVA-Pt2 expressed higher platinum intracellular uptake than cisplatin. NP-UVA-Pt2 demonstrated fast and robust response to photo irradiation while the nanoparticles were stable in PBS at PH7.4 in the dark. The great drug efficacy of NP-UVA-Pt2 under UVA irradiation and the ineffectiveness in the dark makes NP-UVA-Pt2 an ideal light responsive on-demand drug delivery system. Hence, NP-UVA-Pt2 will be a promising platinum based drug in the near future.
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, People's Republic of China.
authors.forename: Rong
authors.initials: R
authors.lastname: Du
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, People's Republic of China.
authors.forename: Haihua
authors.initials: H
authors.lastname: Xiao
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, People's Republic of China.
authors.forename: Guannan
authors.initials: G
authors.lastname: Guo
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Jiang
authors.affiliation: Jilin Province Key Laboratory on Chemistry and Biology of Natural Drugs in Changbai Mountain, School of life Sciences, Northeast Normal University, Changchun 130024, People's Republic of China.
authors.forename: Xing
authors.initials: X
authors.lastname: Yan
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, People's Republic of China; Jilin Medical College, Jilin 132013, People's Republic of China. Electronic address: liwl100@nenu.edu.cn.
authors.forename: Wenliang
authors.initials: W
authors.lastname: Li
authors.affiliation: Jilin Province Key Laboratory on Chemistry and Biology of Natural Drugs in Changbai Mountain, School of life Sciences, Northeast Normal University, Changchun 130024, People's Republic of China.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Yang
authors.affiliation: Jilin Province Key Laboratory on Chemistry and Biology of Natural Drugs in Changbai Mountain, School of life Sciences, Northeast Normal University, Changchun 130024, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Jilin Province Key Laboratory on Chemistry and Biology of Natural Drugs in Changbai Mountain, School of life Sciences, Northeast Normal University, Changchun 130024, People's Republic of China. Electronic address: wenliangl@ciac.ac.cn.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, People's Republic of China. Electronic address: xbjing@ciac.ac.cn.
authors.forename: Xiabin
authors.initials: X
authors.lastname: Jing
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D065546:Drug Liberation / Q000502:physiology*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D010984:Platinum / Q000008:administration & dosage / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D010984:Platinum; D002945:Cisplatin
keywords: Drug delivery system; On-demand drug release; Platinum drug