Abstract 2451: The nuclear-targeted gold nanoparticles inhibit the tumor growth in mouse model as potential anticancer agents

Abstract

The use of gold nanoparticles (AuNPs) as chemotherapeutic agents, based on their intrinsic antineoplastic properties is becoming an increasingly exciting possibility for the treatment of cancer. The specific targeting of AuNPs to the nucleus of malignant cells can be achieved via peptide functionalization of the nanoparticle surface, resulting in DNA damage and subsequent apoptosis. Here, we utilized these novel AuNPs for systemic delivery in vivo and determined their efficacy as chemotherapeutic agents. In addition, we assessed their effects on overall health in order to characterize their systemic toxicity. AuNPs (30 nm in diameter) were functionalized with an Arg-Gly-Asp (RGD) peptide sequence, providing tumor cell specific targeting, as well as a Lys-Lys-Lys-Arg-Lys nuclear localization sequence (NLS) peptide. These novel nuclear-targeting AuNPs were delivered via tail vein injection in nude mice bearing Tu212 tumors. Their in vivo therapeutic efficacy was evaluated, along with assessing their systemic toxicity. The AuNPs, specifically targeted to the tumor cell nucleus, exhibit circulation half-life of 4.1 h, which is exceptionally greater than common chemotherapeutic agents and, although they exhibit uptake by organs of the reticuloendothelial system (RES) (e.g. liver and spleen), they also accumulate in the tumor. In addition, when systemically delivered at low doses (5 nM AuNPs) these novel targeted AuNPs show significant tumor regression (via DNA damage and subsequent apoptosis) when compared to their non-targeting counterparts (P = 0.004), with no observed toxicity in terms of hepatic function, renal function, or body weight. In conclusion, by delivering AuNPs to the nucleus of tumor cells, at low doses in vivo, high therapeutic efficacy is achieved with minimal side effects, indicating the potential for the use of these novel nuclear-targeted AuNPs as chemotherapeutic agents.

Citation Format: Xianghong Peng, Megan A. Macke, Hyung Ju C Shin, Sreenivas Nannapaneni, Nelson Chen, Sungjin Kim, Zhuo (Georgia) Chen, Mostafa A El-Sayed, Dong Shin. The nuclear-targeted gold nanoparticles inhibit the tumor growth in mouse model as potential anticancer agents. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2451. doi:10.1158/1538-7445.AM2015-2451