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Anchored protease-activatable polymersomes for molecular diagnostics of metastatic cancer cells

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Abstract

Real-time quantitative and qualitative analyses of metastasis-associated proteases are critical for precise diagnosis and novel therapeutic treatment of advanced cancers. However, conventional methods based on DNA, peptides, and proteins require sophisticated chemistry and additional processes to expose detection moieties, and they lack elements of temporal control, which limit their applicability. We designed unique protease-activatable polymersomes (PeptiSomes) for high sensitivity, in situ quantitative analysis of activating membrane-type 1 matrix metalloproteinases (MT1-MMP, MMP14). To do this, we first synthesized an amphiphilic block polymer–peptide and a copolypeptide based on mPEG-b-pLeu and MT1-peptide-b-pLeu, respectively. Amphiphilic self-assembled PeptiSomes in water were capable of disassembling and releasing the encapsulated self-quenched fluorescence dye (calcein) via enzymatic activation by MT1-MMP. Our PeptiSome system may potentially prevent the initiation and progression of cancer metastasis. Furthermore, the PeptiSome approach described here is likely to facilitate the development of rapid protease assay techniques and further extend the role of proteases as metastasis indicators and therapeutic targets.

Graphical abstract: Anchored protease-activatable polymersomes for molecular diagnostics of metastatic cancer cells

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Publication details

The article was received on 19 Jun 2017, accepted on 15 Nov 2017 and first published on 16 Nov 2017


Article type: Paper
DOI: 10.1039/C7TB01675A
Citation: J. Mater. Chem. B, 2017, Advance Article
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    Anchored protease-activatable polymersomes for molecular diagnostics of metastatic cancer cells

    H. Kim, J. Lim, J. Choi, H. Lee, H. Y. Son, J. Kim, G. Park, H. Chun, D. Song, Y. Huh and S. Haam, J. Mater. Chem. B, 2017, Advance Article , DOI: 10.1039/C7TB01675A

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