Renal Clearable Chiral Manganese Oxide Supraparticles for In Vivo Detection of Metalloproteinase-9 in Early Cancer Diagnosis

Abstract

In this study, polypeptide TGGGPLGVARGKGGC-induced chiral manganese dioxide supraparticles (MnO₂ SPs) are prepared for sensitive quantification of matrix metalloproteinase-9 (MMP-9) in vitro and in vivo. The results show that L-type manganese dioxide supraparticles (L-MnO₂ SPs) exhibited twice the affinity for the cancer cell membrane receptor CD47 (cluster of differentiation, integrin-associated protein) than D-type manganese dioxide supraparticles (D-MnO₂ SPs) to accumulate at the tumor site after surface modification of the internalizing arginine-glycine-aspartic acid (iRGD) ligand, specifically reacting with the MMP-9, disassembling into ultrasmall nanoparticles (NPs), and efficiently underwent renal clearance. Furthermore, L-MnO₂ facilitates the quantification of MMP-9 in mouse tumor xenografts, as demonstrated by circular dichroism (CD) and magnetic resonance imaging (MRI) within 2 h. A strong linear relationship is observed between MMP-9 concentration and both CD and MRI intensity, ranging from 0.01 to 10 ng mL⁻¹. The corresponding limits of detection (LOD) are 0.0054 ng mL⁻¹ for CD and 0.0062 ng mL⁻¹ for MRI, respectively. hese SPs provide a new approach for exploring chiral advanced biosensors for early diagnosis of cancer.