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

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.