Your browser doesn't support javascript.
loading
MMP-2-responsive fluorescent nanoprobes for enhanced selectivity of tumor cell uptake and imaging.
Sun, Lu; Xie, Shuping; Ji, Xiuru; Zhang, Jingming; Wang, Dongmei; Lee, Seung Jin; Lee, Hyukjin; He, Huining; Yang, Victor C.
Afiliação
  • Sun L; Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China. hehuining@tmu.edu.cn.
Biomater Sci ; 6(10): 2619-2626, 2018 Sep 25.
Article em En | MEDLINE | ID: mdl-30109310
It is difficult to develop highly selective substrate-based fluorescent nanoprobes for specific matrix metalloproteinases (MMPs) due to overlapping substrate specificities among the family of MMP enzymes. To resolve this issue, we have developed novel fluorescent nanoprobes that are highly selective for soluble MMP-2. Herein, MMP-2-responsive nanoprobes were prepared by immobilizing fluorescent fusion proteins on nickel ferrite nanoparticles via the His-tag nickel chelation mechanism. The fusion protein consisted of a fluorescent mCherry protein with a cell penetrating peptide (CPP) moiety. An MMP-2 cleavage site was also introduced within the fusion protein, which was directly linked to the nickel ferrite nanoparticles. The selectivity of nanoprobes was modulated by hiding the cleavage site of MMP-2 substrates deeply inside the system, which could result in strong steric hindrance between the nanoprobes and MMPs, especially for membrane-tethered MMPs such as MMP-14. A cell-based assay demonstrated that the nanoprobes could only be activated by tumor cells secreting soluble MMP-2, but not membrane-tethered MMP-14. To further evaluate the contribution of the steric hindrance effect on the nanoprobes, a truncated recombinant MMP-14 was employed to confer their cleavage activity as compared to native membrane-tethered MMP-14. Furthermore, a designed probe with a diminished steric hindrance effect was proved to be activated by membrane-tethered type MMP-14. The results indicated that the design of fluorescent nanoprobes employing the steric hindrance effect can greatly enhance the selectivity of MMP-responsive nanoprobes realizing the specific detection of soluble MMP-2 in a tumor microenvironment. We believe that highly selective MMP-2-responsive fluorescent nanoprobes have broad impacts on biomedical applications including molecular imaging and labeling for tumor detection.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Recombinantes de Fusão / Compostos Férricos / Metaloproteinase 2 da Matriz / Nanopartículas / Peptídeos Penetradores de Células / Corantes Fluorescentes / Proteínas Luminescentes / Níquel Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Recombinantes de Fusão / Compostos Férricos / Metaloproteinase 2 da Matriz / Nanopartículas / Peptídeos Penetradores de Células / Corantes Fluorescentes / Proteínas Luminescentes / Níquel Idioma: En Ano de publicação: 2018 Tipo de documento: Article