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Cisplatin-tethered gold nanoparticles that exhibit enhanced reproducibility, drug loading, and stability : a step closer to pharmaceutical approval?

Craig, Gemma E. and Brown, Sarah D. and Lamprou, Dimitrios A. and Graham, Duncan and Wheate, Nial J. (2012) Cisplatin-tethered gold nanoparticles that exhibit enhanced reproducibility, drug loading, and stability : a step closer to pharmaceutical approval? Inorganic Chemistry, 51 (6). pp. 3490-3497. ISSN 0020-1669

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Abstract

Gold nanoparticles (AuNPs) can be used as delivery vehicles for platinum anticancer drugs, improving their targeting and uptake into cells. Here, we examine the appropriateness of different-sized AuNPs as components of platinum-based drug-delivery systems, investigating their controlled synthesis, reproducibility, consistency of drug loading, and stability. The active component of cisplatin was tethered to 25, 55, and 90 nm AuNPs, with the nanoparticles being almost spherical in nature and demonstrating good batch-to-batch reproducibility (24.37 +/- 0.62, 55.2 +/- 1.75, and 89.1 +/- 2.32 nm). The size distribution of 25 nm AuNPs has been significantly improved, compared with a previous method that produces polydispersed nanoparticles. Attachment of platinum to the AuNP surface through a poly(ethylene glycol) (PEG) linker exhibits an increase in the drug loading with increasing particle size: 25 nm (815 +/- 106 drug molecules per AuNP), SS nm (14216 +/- 880), and 90 nm (54487 +/- 15996). The stability of the naked, PEGylated, and platinum-conjugated nanoparticles has been examined over time under various conditions. When stored at 4 degrees C, there is minimal variation in the diameter for all three AuNP sizes; variation after 28 days for the 25 nm AuNPs was 2.4%; 55 nm, 3.3%; and 90 nm, 3.6%. The 25 nm AuNPs also demonstrate minimal changes in UV-visible absorbance over the same time period.