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iRGD-Mediated and Enzyme-Induced Precise Targeting and Retention of Gold Nanoparticles for the Enhanced Imaging and Treatment of Breast Cancer.

Despite the great achievements of nanomedicines made in cancer chemotherapy, precise tumor targeting and deep penetration are still major challenges. Many nanomedicines can only passively accumulate near leaky site of tumor vessels through the enhanced permeability and retention (EPR) effect and cannot reach the deep region of tumor. To improve the tumor targeting, penetration and retention efficiency, an iRGD-mediated and enzyme-induced precise targeting gold nanoparticles system (iRGD/AuNPs-A&C) was developed by simply coadministering a tumor-homing penetration peptide iRGD (CRGDKGPDC) with a legumain responsive aggregable gold nanoparticle (AuNPs-A&C). In vitro, iRGD/AuNPs-A&C showed a consistent increase rate in size with AuNPs-A&C, suggesting that iRGD/AuNPs-A&C could also aggregate in the presence of legumain, which was in favor of the enhanced retention in tumor microenvironment. Meanwhile, iRGD/AuNPs-A&C showed higher 4T1 cells cellular uptake in vitro and presented higher penetration and accumulation in breast tumor in vivo than AuNPs-A&C, leading to enhanced tumor imaging efficacy and the improved chemotherapeutic effect to 4T1-bearing mice. These results suggested that the iRGD-mediated and enzyme-induced dual-functional nanoplatform was promising for the 4T1 tumor imaging and treatment.

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