Gold Nanoparticles for the Improved Anticancer Drug Delivery of the Active Component of Oxaliplatin

Abstract

The platinum-based anticancer drugs cisplatin, carboplatin, and oxaliplatin are an important component of chemotherapy but are limited by severe dose-limiting side effects and the ability of tumors to develop resistance rapidly. These drugs can be improved through the use of drug-delivery vehicles that are able to target cancers passively or actively. In this study, we have tethered the active component of the anticancer drug oxaliplatin to a gold nanoparticle for improved drug delivery. Naked gold nanoparticles were functionalized with a thiolated poly(ethylene glycol) (PEG) monolayer capped with a carboxylate group. [Pt(1R,2R-diaminocyclohexane)(H2O)2]2NO3 was added to the PEG surface to yield a supramolecular complex with 280 (±20) drug molecules per nanoparticle. The platinum-tethered nanoparticles were examined for cytotoxicity, drug uptake, and localization in the A549 lung epithelial cancer cell line and the colon cancer cell lines HCT116, HCT15, HT29, and RKO. The platinum-tethered nanoparticles demonstrated as good as, or significantly better, cytotoxicity than oxaliplatin alone in all of the cell lines and an unusual ability to penetrate the nucleus in the lung cancer cells.

Evaluation of cytotoxicity and radiation enhancement using 1.9 nm gold particles: potential application for cancer therapy

“…A variety of different cancer therapeutic strategies have focused on the use of gold nanoparticles including the targeted delivery of anti-cancer agents including methotrexate [5] tamoxifen [6] and oxaliplatin [7], radio frequency radiation [8], thermal ablation [9,10] and metal enhanced radiotherapy [11].…”

Characterisation of gold nanoparticles synthesised by leaf and seed extract ofSyzygium cuminiL.

“…Among various synthesis methods, plant-mediated synthesis is preferred due to its cost effectiveness and environment-friendly nature [3,4]. GNP have applications in therapeutic [5], catalysis [2], immunoassay and immunosensing [6], diagnostic and drug delivery [7][8][9][10], analyte sensing [11][12][13], cancer cell diagnostics and selective photothermal therapy [14,15], photoacoustic imaging [16,17] and cancer treatment [18]. Various plant extracts have been explored for the synthesis of GNP, namely tamarind [19], Aloe vera [20], Pelargonium graveolens [21], Diopyros kaki [22], Eucalyptus camaldulensis and Pelargonium roseum [23], coriander [24], Scutellaria barbata [25], lemongrass [26], Datura metel, Carica papaya and Solanum melongena [27].…”

Advancements in Polymer Science: ‘Smart’ Drug Delivery Systems for the Treatment of Cancer

“…Among the external stimuli, pH gradients have been widely used for controlled release relying on the abnormally low pH of endosomes and tumor tissues compared to healthy tissues. [12][13][14][15] To further enhance their capabilities, "smart" polymers and nanoparticles are capable of controlled release of their cargo as well as being able to target specific sites in order to efficiently deliver therapies. Polymers provide advantages over other cancer immunotherapies if they can load both tumor macromolecules and adjuvants, and through specific sizes and functional moieties be selectively delivered to specific target sites.…”