Investigation of Properties of Anti-Prostate Specific Membrane Antigen-targeted Gold Nanoparticles as Drug Carriers in Tumor Therapy

Specific targeted delivery and control drug release are desirable properties of a drug for tumor therapy. Nanomedicine, the science that studies the application of nanotechnology to disease treatment, might be of help. Targeted nanoparticles (NP) for their size and structure are able to enhance the accumulation in the tumor of encapsulated or linked / adsorbed molecules (gene, drug). We have therefore investigated the binding properties of gold-NPs (20 nm) conjugated to D2/B, a mAb recognizing the prostate specific membrane antigen (PMSA). PSMA for its wide distribution in prostate tumor (about 70-80% of patients are PSMA+), is an important biomarker in the management of this malignancy using targeted drugs. Gold-NPs have been synthesized by laser ablation, mixed with a reporter solution (Texas red) and treated with a thiol-PEG solution. Derivatization of PEG-COOH with EDC/Sulfo NHS has been used to covalently link the mAb to the NPs. D2/B-NP binding to LNCaP (PSMA+) cells has been assessed by cytometry. We have measured a MFI (mean fluorescence value) of 1,383 for D2/B-NP whereas the MFI of the negative control (CTRL-) was 68. The binding specificity was confirmed on PSMA– Jurkat cells (MFI of 121 and 101 for D2/B-NP and CTRL-, respectively). Binding and internalization of D2/B-NP in LNCaP cells were assayed by confocal microscopy; detection of D2/B-NP by surface-enhanced Raman scattering also revealed the selective binding of the NPs to Ag+ cells. The results of specific delivery and internalization support our idea to use mAb anti-PSMA targeted NPs to enhance the transport of toxic drugs in the tumor