Tumor-triggered transformation of chimeric peptide for dual-stage-amplified magnetic resonance imaging and precise photodynamic therapy.

Abstract

Despite the great success in clinical magnetic resonance imaging (MRI), Gd³⁺-based contrast agents still suffer from low proton relaxation efficiency, rapid metabolic clearance as well as poor sensitivity. In this work, we designed a matrix metalloproteinase-2 (MMP-2) responsive chimeric peptide for dual-stage-amplified MRI and precise photodynamic therapy. Both in vitro and in vivo studies indicated that this chimeric peptide could self-assembly into spherical nanoparticles at physiological condition with r₁ value of 28.17 mM^-1s^-1. Meanwhile, the spherical shape endowed chimeric peptide with efficient tumor accumulation via enhanced penetration and retention (EPR) effect. Importantly, the overexpressed MMP-2 in tumor region could specifically hydrolyze chimeric peptide, leading to sphere-to-fiber transformation. This transformation enhanced both the tumor accumulation and the relaxivity of contrast agent. Consequently, the r₁ value was remarkably elevated to 51.52 mM^-1s^-1, which guided precise photodynamic therapy. This tumor microenvironment-triggered transformable strategy should show great potential for tumor-targeted imaging and phototherapy.