PSMA1-mediated ultrasmall gold nanoparticles facilitate tumor targeting and MR/CT/NIRF multimodal detection of early-stage prostate cancer

Prostate-specific membrane antigen (PSMA) is a prominent biomarker for prostate cancer (PCa) diagnosis. Safe contrast agents able to render the expression and distribution of PSMA would facilitate early accurate screening and prognostic prediction of PCa. However, current Gd-containing nanoparticles are often limited by nonspecific redistribution in mononuclear phagocyte system (MPS) and inadequate perfusion to target sites. Besides, intrinsic defects of magnetic resonance (MR) equipment also hamper their use for precisely depicting PSMA details. Herein, we devised a novel noninvasive MR/CT/NIRF multimodal contrast agent (AGGP) coordinated to a high-affinity PSMA ligand (PSMA1) to specifically detect and quantify PSMA expression in PCa lesions, which exhibited formidable tripe-modal signal augments, preferential PSMA targeting, effective MPS escaping and profitable renal-clearable behavior in living mice. Biocompatibility and histopathological studies substantiated high security of AGGP in vivo, opening the door to future opportunities for improving early-stage PCa detection and clinical implementation of more effective multifunctional nanotherapeutics. Herein, we devised a multimodal contrast agent (AGGP) featured on highly-effective PSMA targeting and desired molecular pharmacokinetics for PCa diagnosis. By superimposing Au and Gd motifs into glutathione scaffold, AGGP achieved tripe-modal imaging capacities including T1-MR relaxivity, CT attenuation and fluorescence properties. Taking advantage of EPR effect, AGGP was inclined to penetrate dysfunctional endothelia and entrapped within tumor parenchyma. By conjugating PSMA1, AGGP conduced active targeting to PSMA-overexpressed PCa. As a result, AGGP revealed promoted specific-site accumulation, prolonged signal enhancements and high biosecurity, thus we anticipated this noninvasive MR/CT/NIRF strategy a favorable choice for bio-imaging molecular evaluation for PCa lesions. [Display omitted]