Activatable T1 Relaxivity Recovery Nanoconjugates for Kinetic and Sensitive Analysis of Matrix Metalloprotease 2

5 years ago

Activatable T1 Relaxivity Recovery Nanoconjugates for Kinetic and Sensitive Analysis of Matrix Metalloprotease 2

Zhong Chen, Lengceng Ma, Lirong Wang, Xiaoxue Tang, Hongyu Lin, Xianglong Zhu, Jinhao Gao

Sensitive detection of matrix metalloproteinase 2 (MMP-2, an important cancer marker associated with tumor invasion and metastasis) activity in vitro and at cellular level is of great significance to clinical diagnosis and medical treatment. With unique physical properties, nanoparticles are emerging as a platform for the construction of conjugates of various biological molecules, which can be expected to generate new types of biosensors. In this work, Fe₃O₄ NPs were modified with Gd chelates via linking peptides to construct NP–substrate (Fe₃O₄–pep–Gd) conjugates for kinetic MMP-2 activity assessment in vitro at the cellular level and in vivo. Superparamagnetic Fe₃O₄ quenched the longitudinal relaxation effect (T₁ relaxivity) of the attached Gd chelates by perturbing proton relaxation process under an external magnetic field. MMP-2 cleaved the peptide substrates and released Gd chelates from the local magnetic fields accompanied by T₁ relaxivity recovery and T₁ contrast enhancement. Benefiting from signal amplification through binding multiple Gd chelates to one linking peptide, Fe₃O₄–pep–Gd conjugates exhibited high sensitivity for the detection of MMP-2 (as low as 0.5 nM). Enzymatic processes were in good agreement with the integrated Michaelis–Menten model, revealing an unexpected activity enhancement in the initial stage. Fe₃O₄–pep–Gd conjugates could also probe MMP-2 at cellular level and in vivo that indicates a great promise in in vitro diagnosis (IVD) and disease monitoring.

Publisher URL: http://dx.doi.org/10.1021/acsami.7b05389

DOI: 10.1021/acsami.7b05389