The synthesis and evaluation of polymer prodrug/collagen hybrid gels for delivery into metastatic cancer cells

• Published in: Nanomedicine 2013-08, Vol.9 (6), p.767-775
• Main Authors: Kojima, Chie, PhD, Nishisaka, Eiko, MS, Suehiro, Tomoyuki, MS, Watanabe, Kenji, MS, Harada, Atsushi, PhD, Goto, Tatsushi, PhD, Magata, Yasuhiro, PhD, Kono, Kenji, PhD
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Collagen; Collagen - administration & dosage; Collagen - chemistry; Dendrimer; Dendrimers - administration & dosage; Dendrimers - chemistry; Drug delivery; Drug Delivery Systems; Humans; Hydrogel; Hydrogel, Polyethylene Glycol Dimethacrylate - chemistry; Internal Medicine; MCF-7 Cells; Metastasis; Mice; Neoplasm Metastasis - drug therapy; Neoplasm Metastasis - pathology; Neoplasms - drug therapy; Neoplasms - pathology; Polymers - chemical synthesis; Polymers - chemistry; Prodrugs - administration & dosage
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2013.01.004

Abstract 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. From the Clinical Editor 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.