Fabrication of polymer-platinum(II) complex nanomicelle from mPEG-g-alpha,beta-poly [(N-amino acidyl)-DL-aspartamide] and cis-dichlorodiammine platinum(II) and its cytotoxicity.
The aim of research is to develop and optimize delivery system for cis-dichlorodiammine platinum(II) (CDDP) based on polymer-metal complex nanomicelles with controllable particle size in order to achieve the passive tumor targeting. In particular, graft copolymers, mPEG-g-alpha,beta-poly [(N-amino acidyl)-DL-aspartamide] (mPEG-g-PAAsp) were synthesized by the ring-opening reaction of polysuccinimide with mPEG-NH(2) (M(w): 2000 and 5000 Da), and then with l-aspartic acid and l-glutamic acid, respectively. mPEG-g-PAAsp-CDDP complex nanomicelles were fabricated from mPEG-g-PAAsp and CDDP. The formation of mPEG-g-PAAsp-CDDP nanomicelles was confirmed by fluorescence spectrophotoscopy, electrical conductivity and particle size measurements. It was found that all the nanomicelles showed spherical shapes with clear core-shell structures and narrow size distributions. Their sizes ranged from 80 to 160 nm, suggesting of their passive targeting potential to tumor tissue. With the increase of the molecular weight of mPEG, the sizes of mPEG-g-PAAsp-CDDP micelles showed a tendency to increase. mPEG-g-PAAsp-CDDP nanomicelles showed linear gradual drug release profiles in 40 h, suggestion of their sustained drug release behaviors. Compared with CDDP, mPEG-g-PAAsp-CDDP micelles showed essential decreased cytotoxicity to Bel-7402 cell line.
Wang
Chengyun
C
College of New Drug Innovation Research & Development, East China Normal University, Shanghai 200062, PR China.
Gong
Yanbao
Y
Fan
Naiqian
N
Liu
Shunying
S
Luo
Shufang
S
Yu
Jiahui
J
Huang
Jin
J
D001224:Aspartic Acid / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival; D002945:Cisplatin / Q000737:chemistry*; D016503:Drug Delivery Systems; D018698:Glutamic Acid / Q000737:chemistry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008956:Models, Chemical; D010455:Peptides / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared
D008823:Micelles; D010455:Peptides; D011108:Polymers; C543071:mPEG-g-alpha,beta-poly((N-amino acidyl)-DL-aspartamide); D001224:Aspartic Acid; D018698:Glutamic Acid; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; D002945:Cisplatin