Abstract
Gold nanoparticle (GNP) as a promising theranostic probe has been increasingly studied. The tumor-targeting efficiency of GNPs is crucial to increase the therapeutic ratio. In this study, we developed PSMA-targeted GNPs to enhance GNP uptake in prostate cancer and developed an x-ray fluorescence imaging system to noninvasively monitor and assess GNP delivery.
For targeted therapy of prostate cancer, anti-prostate-specific membrane antigen (PSMA) antibodies were conjugated onto the PEGylated GNPs through EDC/NHS chemistry. In vivo imaging was implemented using an in-house-developed dual-modality CT/XFCT system on mice bearing subcutaneous LNCaP prostate tumors. Following the intravenous administration of GNPs (15mg/ml, 200μL), the x-ray fluorescence signals from the tumor were collected at various timepoints (5min∼30hrs) for GNP pharmacokinetics analysis. At 24hrs post administration, x-ray fluorescence projection (XRFproj) and computed tomographic (XFCT) imaging were conducted to evaluate the prostate tumor uptake of active- and passive-targeting GNPs. Inductively coupled plasma mass spectrometry analysis (ICP-MS) was adopted as a benchmark to verify the quantification accuracy of XRFproj/XFCT imaging.
Fluorescence microscopic imaging confirmed the enhanced (∼4 times) targeting efficiency of PSMA-targeted GNPs in vitro. The pharmacokinetics analysis demonstrated enhanced tumor uptake/retention of PSMA-targeted GNPs and revealed that the peak tumor accumulation appeared at ∼24hrs post intravenous administration. Both XRFproj and XFCT imaging presented their accuracy in quantifying GNPs within tumor non-invasively. Moreover, XFCT imaging verified its unique capabilities to simultaneously determine the heterogeneous spatial distribution and the concentration of GNPs within tumors in vivo.
In conjunction with PSMA-targeted GNPs, XRFproj/XFCT would be a highly sensitive tool for targeted imaging of prostate cancer, benefiting the elucidation of mechanisms of GNP-assisted prostate-cancer therapy.
