The role of the size and number of polyethylene glycol chains in the biodistribution and tumor localization of triazine dendrimers.
The synthesis and biodistribution of three triazine dendrimers differing in PEGylation are described. Dendrimers 1, 2, and 3 are derived from a common intermediate, dendrimer 4, and vary in molecular mass from 11 to 73 kDa as a result of PEGylation with multiple (theoretically, 16) PEG groups of 0.6, 2, and 5 kDa, respectively. As expected, elimination half-lives increased with an increase in molecular mass. In light of other results, however, molecular mass proves not to be the primary determinant of elimination half-lives. Instead, these times can be more readily predicted from the number of PEG groups on the dendrimer: the size of the PEG chain contributes to a lesser extent. Tumor uptake is observed for all the three dendrimers in mice bearing prostate cancer xenografts.
Lim
Jongdoo
J
Department of Chemistry, Texas A&M University, College Station, TX 77843-3255, USA.
Guo
Yi
Y
Rostollan
Cynthia L
CL
Stanfield
Jennifer
J
Hsieh
Jer-Tsong
JT
Sun
Xiankai
X
Simanek
Eric E
EE
D000818:Animals; D045744:Cell Line, Tumor; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015394:Molecular Structure; D008970:Molecular Weight; D009369:Neoplasms / Q000473:pathology*; D011092:Polyethylene Glycols / Q000737:chemistry*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D014018:Tissue Distribution; D014227:Triazines / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
D050091:Dendrimers; D014227:Triazines; D011092:Polyethylene Glycols