Anchored protease-activatable polymersomes for molecular diagnostics of metastatic cancer cells. Issue 48 (1st December 2017)

• Record Type: Journal Article
• Authors: Kim, Hyun-Ouk; Lim, Jong-Woo; Choi, Jihye; Lee, Hwunjae; Son, Hye Young; Kim, Jihye; Park, Geunseon; Chun, Haejin; Song, Daesub; Huh, Yong-Min; Haam, Seungjoo
• Is Part Of: Journal of materials chemistry. Volume 5:Issue 48(2017)
• Page Start: 9571
• Page End: 9578
• Publication Date: 2017-12-01
• Subjects: Materials -- Periodicals; Chemistry, Analytic -- Periodicals; Biomedical materials -- Research -- Periodicals; 543.0284
• DOI: 10.1039/c7tb01675a
• Languages: English
• ISSNs: 2050-750X

Abstract

Abstract : We have designed unique protease-activatable polymersomes (PeptiSomes) for in situ quantitative analysis with high selectivity towards MT1-MMP. 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.