Neuropilin-1-Targeted Gold Nanoparticles Enhance Therapeutic Efficacy of Platinum(IV) Drug for Prostate Cancer Treatment

Abstract

Platinum-based anticancer drugs such as cisplatin, oxaliplatin, and carboplatin are some of the most potent chemotherapeutic agents but have limited applications due to severe dose-limiting side effects and a tendency for cancer cells to rapidly develop resistance. The therapeutic index can be improved through use of nanocarrier systems to target cancer cells efficiently. We developed a unique strategy to deliver a platinum(IV) drug to prostate cancer cells by constructing glutathione-stabilized (Au@GSH) gold nanoparticles. Glutathione (GSH) has well-known antioxidant properties, which lead to cancer regression. Here, we exploit the advantages of both the antioxidant properties and high surface-area-to-volume ratio of Au@GSH NPs to demonstrate their potential for delivery of a platinum(IV) drug by targeting the neuropilin-1 receptor (Nrp-1). A lethal dose of a platinum(IV) drug functionalized with the Nrp-1-targeting peptide (CRGDK) was delivered specifically to prostate cancer cells in vitro. Targeted peptide ensures specific binding to the Nrp-1 receptor, leading to enhanced cellular uptake level and cell toxicity. The nanocarriers were themselves nontoxic, but exhibited high cytotoxicity and increased efficacy when functionalized with the targeting peptide and drug. The uptake of drug-loaded nanocarriers is dependent on the interaction with Nrp-1 in cell lines expressing high (PC-3) and low (DU-145) levels of Nrp-1, as confirmed through inductively coupled plasma mass spectrometry and confocal microscopy. The nanocarriers have effective anticancer activity, through upregulation of nuclear factor kappa-B (NF-κB) protein (p50 and p65) expression and activation of NF-κB-DNA-binding activity. Our preliminary investigations with platinum(IV)-functionalized gold nanoparticles along with a targeting peptide hold significant promise for future cancer treatment.

In Situ Formation of Dual‐Phase Thermosensitive Ultrasmall Gold Nanoparticles

“…Gold nanoparticles (GNPs) have attracted considerable attention in recent years due to their potentiala pplications in aw ider ange of areas, such as catalysis, [1] biosensing, [2] drug delivery, [3] molecular electronics, [4] ands urfacep atterning. [5] In particular, ultrasmall gold nanoparticles (USGNPs) with sizes in the 1-3 nm range are of great interestb ecause of their unique properties compared to those larger than 5nm.…”

Cerium oxide nanoparticles inhibit the migration and proliferation of gastric cancer by increasing DHX15 expression

“…Moreover, recent studies have also shown that neuropilin-1-targeted gold nanoparticles enhanced the effect of platinum(IV) in prostate cancer by upregulating the protein level of NF-KB (p65) and its DNA binding ability. 33 According to the results of this and other recent studies, we believe that CNPs inhibit proliferation and migration of cancer cells by activating the expression of DHX15 and its downstream signal pathway.…”

Characterization and Antitumor Activity of Chitosan/Poly (Vinyl Alcohol) Blend Doped with Gold and Silver Nanoparticles in Treatment of Prostatic Cancer Model

“…Additionally, gold nanoparticles (AuNPs) have attracted much attention in the field of biomedical imaging and clinical diagnostics, in the last decade [45,46]. These NPs can also be surface modified by attaching targeting ligands and tagged with imaging molecules for specificity and effectiveness of the cancer diagnosis and therapeutics [39].…”