The synthesis and evaluation of polymer prodrug/collagen hybrid gels for delivery into metastatic cancer cells.
Metastatic cancer cells degrade extracellular matrix containing collagen. In this study, a variety of different polymer prodrugs have been synthesized and embedded in collagen gels for application in a metastasis-associated drug delivery system (DDS). Dendrimer-doxorubicin (Dox) prodrugs were prepared with different surfaces, including collagen peptides and polyethylene glycol. Furthermore, Dox was conjugated to linear poly(glutamic acid) (poly-Glu) instead of the dendrimer. The cytotoxicities of each of these polymer prodrug systems against the poorly invasive MCF-7 and highly invasive MDA-MB-231 cells were similar. The highly invasive MDA-MB-231 cells, however, were more sensitive than the MCF-7 cells to the polymer prodrugs-embedded collagen gels, suggesting that these polymer prodrugs/collagen hybrid gels would be useful for the development of metastasis-associated DDSs. The cytotoxicities of the polymer prodrugs were dependent on their chemical compositions. The collagen peptide-conjugated dendrimer prodrug/collagen hybrid gel demonstrated in vivo anticancer effects in an orthotopic metastatic mouse model.


BACKGROUND
In this study, a variety of polymer prodrugs have been synthesized and embedded in collagen gels to be used in a metastasis-associated drug delivery system, demonstrating in vivo anticancer effects in an orthotopic metastatic mouse model.
Nanoscience and Nanotechnology Research Center, Research Organization for the 21st Century, Osaka Prefecture University, Naka-ku, Sakai, Osaka, Japan. c-kojima@21c.osakafu-u.ac.jp
Chie
C
Kojima
Eiko
E
Nishisaka
Tomoyuki
T
Suehiro
Kenji
K
Watanabe
Atsushi
A
Harada
Tatsushi
T
Goto
Yasuhiro
Y
Magata
Kenji
K
Kono
D000818:Animals; D003094:Collagen / Q000008:administration & dosage / Q000737:chemistry; D050091:Dendrimers / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D061986:MCF-7 Cells; D051379:Mice; D009362:Neoplasm Metastasis / Q000188:drug therapy* / Q000473:pathology; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry; D011355:Prodrugs / Q000008:administration & dosage*
D050091:Dendrimers; D011108:Polymers; D011355:Prodrugs; C418362:collagen-based sealant GAO; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D003094:Collagen
Collagen; Dendrimer; Drug delivery; Hydrogel; Metastasis