PEI-derivatized fullerene drug delivery using folate as a homing device targeting to tumor.
Fullerene (C60) has shown great potential in drug delivery. In this study, firstly, amine-functionalized C60 (C60-NH(2)) was achieved by introducing ethylenediamine onto the surface of C60, and then PEI-derivatized C60 (C60-PEI) was performed via a cationic polymerization of aziridine on the surface of C60-NH(2); FT-IR and TGA results verified the structure of water-soluble C60-PEI. C60-PEI was encapsulated with folic acid (FA) through an amide linker, and then docetaxel (DTX) was conjugated to C60-PEI-FA and obtained a drug delivery system, C60-PEI-FA/DTX. Compared with free DTX, the tumor targeting drug delivery could efficiently cross cell membranes, lead to more apoptosis and afford higher antitumor efficacy in a cultured PC3 cells in vitro. Furthermore, compared with free DTX in an in vivo murine tumor model, C60-PEI-FA/DTX afforded higher antitumor efficacy without obvious toxic effects to normal organs owing to its prolonged blood circulation and 7.5-fold higher DTX uptake of tumor, demonstrating that C60-PEI-FA/DTX may be promising for high treatment efficacy with minimal side effects in future therapy.
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China.
Jinjin
J
Shi
Hongling
H
Zhang
Lei
L
Wang
Lulu
L
Li
Honghong
H
Wang
Zhenzhen
Z
Wang
Zhi
Z
Li
Chengqun
C
Chen
Lin
L
Hou
Chaofeng
C
Zhang
Zhenzhong
Z
Zhang
D061605:Administration, Intravenous; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000077143:Docetaxel; D016503:Drug Delivery Systems / Q000379:methods*; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D005492:Folic Acid / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D037741:Fullerenes / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D010316:Particle Size; D011094:Polyethyleneimine / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D043823:Taxoids / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D014018:Tissue Distribution / Q000187:drug effects; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D037741:Fullerenes; D043823:Taxoids; D000077143:Docetaxel; D011094:Polyethyleneimine; D005492:Folic Acid