MMP-2-Controlled Transforming Micelles for Heterogeneic Targeting and Programmable Cancer Therapy

Journal article

Herein, through the active-peptide-functionalization, we developed a nanoscale micelles system (named HEKM) which consists of tumor microenvironment-regulated shape-changing with specific recognition abilities for enhanced cellular targeting, internalization and therapy of heterogeneic tumors. As a result, HEKMs could recognize and bind the tumor heterogeneity marker EGFR-HER2 complex, which led to an enhanced tumor targeting effect. In particular, HEKMs could self-assemble into nanorods under normal physiological conditions while transform into nanospheres in the tumor extracellular microenvironment by a sensitive response to matrix metalloproteinase-2 (MMP-2). The nanorods could prolong the blood circulation time while the nanospheres could accelerate tissue penetration in tumors. In vivo dual-modal targeted imaging was realized by FRET-fluorophore conjugation and gadolinium loading in HEKMs. Tumor cell apoptosis was achieved by proapoptotic element integration. The in vitro and in vivo studies both demonstrated that these rationally designed, shape-changing and targeting micelles could achieve maximized drug efficacy and minimum side effects.

Authors: Wang, Z; Wang, Y; Jia, X; Han, Q; Qian, Y

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Ivyspring International Publisher
• Journal: Theranostics
• Volume: 9
• Issue: 6
• Pages: 1728-1740
• Publication date: 2019-02-28
• DOI: 10.7150/thno.30915
• EISSN: 1838-7640
• ISSN: 1838-7640
• Language: English
• Keywords: Cancer research; Biology; Materials science; Nanorod; Biophysics; In vivo; Targeted therapy; Biochemistry; Tumor microenvironment; Chemistry; Tumor cells; Nanotechnology; Cell; Internalization; Medicine; Cancer cell; Cancer; Matrix metalloproteinase; Extracellular matrix; Micelle