title: Doxorubicin-conjugated dendrimer/collagen hybrid gels for metastasis-associated drug delivery systems.
abstract: Metastasis is a characteristic property of cancer cells, which degrade extracellular matrix containing collagen. We prepared a polymer prodrug-embedded collagen gel for metastasis-associated drug delivery. A collagen peptide-modified dendrimer that attached doxorubicin (Dox) via a pH-degradable linkage was synthesized as a polymer prodrug. Compared with free Dox, the diffusion of the dendrimer prodrug from the collagen gel was suppressed. Highly invasive MDA-MB-231 cells were more sensitive to the prodrug-hybrid collagen gel than poorly invasive MCF-7 cells, even though the cytotoxicity of the dendrimer prodrug by itself against these cells was almost identical. The cytotoxicity against MDA-MB-231 cells decreased in the presence of a matrix metalloproteinase (MMP) inhibitor, suggesting that the dendrimer prodrug/collagen hybrid gel was affected by MMP activity. The dendrimer prodrug/collagen hybrid gel not only suppressed tumor growth but also attenuated metastatic activity in vivo. Therefore, the dendrimer prodrug-embedded collagen gel is useful for cancer chemotherapy.
authors.affiliation: Nanoscience and Nanotechnology Research Center, Research Organization for the 21st Century, Osaka Prefecture University, 1-2, Gakuen-cho, Naka-ku, Sakai, Osaka 599-8570, Japan. c-kojima@21c.osakafu-u.ac.jp
authors.forename: Chie
authors.initials: C
authors.lastname: Kojima
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Suehiro
authors.forename: Kenji
authors.initials: K
authors.lastname: Watanabe
authors.forename: Mikako
authors.initials: M
authors.lastname: Ogawa
authors.forename: Ayano
authors.initials: A
authors.lastname: Fukuhara
authors.forename: Eiko
authors.initials: E
authors.lastname: Nishisaka
authors.forename: Atsushi
authors.initials: A
authors.lastname: Harada
authors.forename: Kenji
authors.initials: K
authors.lastname: Kono
authors.forename: Takashi
authors.initials: T
authors.lastname: Inui
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Magata
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000737:chemistry / Q000494:pharmacology*; D050091:Dendrimers / Q000737:chemistry*; D004058:Diffusion; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D005260:Female; D005782:Gels / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008163:Luminescent Measurements; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D010455:Peptides / Q000494:pharmacology; D012996:Solutions
chemical_list: D050091:Dendrimers; D005782:Gels; D010455:Peptides; D012996:Solutions; D004317:Doxorubicin; D003094:Collagen; D020782:Matrix Metalloproteinases