Journal
ACTA BIOMATERIALIA
Volume 9, Issue 3, Pages 5673-5680Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2012.11.013
Keywords
Collagen; Dendrimer; Metastasis; Drug delivery; Hydrogel
Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT)
- Special Coordination Funds for Promoting Science and Technology of MEXT (Improvement of Research Environment for Young Researchers)
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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 pro-drughybrid 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. (C) 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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