Doxorubicin-conjugated dendrimer/collagen hybrid gels for metastasis-associated drug delivery systems

作者：Kojima Chie^*; Suehiro Tomoyuki; Watanabe Kenji; Ogawa Mikako; Fukuhara Ayano; Nishisaka Eiko; Harada Atsushi; Kono Kenji; Inui Takashi; Magata Yasuhiro

来源：Acta Biomaterialia, 2013, 9(3): 5673-5680.

DOI：10.1016/j.actbio.2012.11.013

• Collagen
• Dendrimer
• Metastasis
• Drug delivery
• Hydrogel

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.

• 出版日期2013-3