Activatable T1 Relaxivity Recovery Nanoconjugates for Kinetic and Sensitive Analysis of Matrix Metalloprotease 2.
Xianglong ZhuHongyu LinLirong WangXiaoxue TangLengceng MaZhong ChenJinhao GaoPublished in: ACS applied materials & interfaces (2017)
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.
Keyphrases
- cell migration
- sensitive detection
- healthcare
- cancer therapy
- magnetic resonance
- mental health
- loop mediated isothermal amplification
- photodynamic therapy
- papillary thyroid
- high throughput
- drug delivery
- squamous cell
- amino acid
- mass spectrometry
- living cells
- nucleic acid
- fluorescence imaging
- smoking cessation
- combination therapy
- molecularly imprinted
- high density
- solid phase extraction
- iron oxide nanoparticles