468253 Evaluation of the Cancer-Preventive Effect of Resveratrol-Loaded Nanoparticles on the Formation of Tumor Spheroids

Monday, November 14, 2016: 1:30 PM
Golden Gate 5 (Hilton San Francisco Union Square)
Elisa A. Torrico-Guzmán, Chemical Engineering, University of Rhode Island, West Warwick, RI and Samantha A. Meenach, Chemical Engineering and Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI

Despite the recent advancements in the treatment of cancer, designing advanced therapeutics remains an enormous challenge for scientists. It is estimated in the U.S. that 1,685,210 new cases of cancer will be diagnosed in 2016 and 595,600 people will die from cancer, corresponding to approximately 1,600 deaths per day[1].

Chemotherapy has been extensively used to combat cancer, however its overall success is rather limited for lung cancer. An emerging alternative over the past few decades has been the use of chemopreventive phytochemicals, which are constituents of fruits and vegetables with potential pharmacological and/or nutritional functions. These agents may reverse or inhibit the carcinogenic process resulting in a decreased cancer risk [2]. The FDA has approved several agents for cancer prevention, including Tamoxifen for breast cancer and the Human Papilloma Virus (HPV) vaccine for cervical intraepithelial neoplasia. More than 200 other chemopreventive agents are being evaluated in clinical trials [3].

Resveratrol (3,5,4′-trihydroxystilbene, RSV) is a phytoalexin, a substance synthesized by plants to counteract pathogens [4]. It is abundantly found in red grapes and in lower amounts in peanuts and blueberries. In 1997, interest in RSV peaked when Jung et al. reported its chemopreventive effects on all stages of neoplastic activity (initiation, promotion and progression) [5]. In vitro studies show the promising properties of resveratrol; however, its limited bioavailability in the bloodstream makes it difficult to translate into clinical studies. A study by Dolfini et al. [6] showed that RSV induces drastic growth inhibition on a human breast cancer cell line in in vivo and in vitro assays. Also, RSV-loaded gel nanoparticles enhanced intracellular uptake and cytotoxicity in a NCI-H460 lung cancer cell line [7] and RSV-loaded nanostructure lipid carriers exhibited higher penetration into the skin in comparison to solid lipid nanoparticles [8], demonstrating improvement with RSV in nanoparticle systems.

The aim of this project was to evaluate the chemopreventive effect of RSV and RSV-loaded nanoparticles (RSV-NP) on the formation of tumor spheroids. We synthesized biodegradable nanoparticles comprised of the biodegradable polymer acetalated dextran loaded with RSV and we evaluated the efficacy of pure RSV and RSV-NP using A549 adenocarcinoma lung cancer cell line in 2D and 3D cell culture studies. 3D multicellular spheroids (MCS) reflect many of the properties of solid tumors and better mimic the barriers of drug diffusion, transport, and distribution within tumors [9, 10]. RSV and RSV-NP exerted an inhibitory effect on the growth of MCS, showing a promising alternative as a chemopreventive drug, which could palliate the incidence or mortality from lung cancer.


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[3] Davis, J.S. and X. Wu, Current state and future challenges of chemoprevention. Discov Med, 2012. 13(72): p. 385-90.

[4] Singh, C.K., M.A. Ndiaye, and N. Ahmad, Resveratrol and cancer: Challenges for clinical translation. Biochim Biophys Acta, 2015. 1852(6): p. 1178-85.

[5] Jang, M., et al., Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science (New York, N.Y.), 1997. 275(5297): p. 218-20.

[6] Dolfini, E., et al., Resveratrol impairs the formation of MDA-MB-231 multicellular tumor spheroids concomitant with ceramide accumulation. Cancer Lett, 2007. 249(2): p. 143-7.

[7] Karthikeyan, S., et al., Anticancer activity of resveratrol-loaded gelatin nanoparticles on NCI-H460 non-small cell lung cancer cells. Biomedicine & Preventive Nutrition, 2013. 3(1): p. 64-73.

[8] Gokce, E.H., et al., Resveratrol-loaded solid lipid nanoparticles versus nanostructured lipid carriers: evaluation of antioxidant potential for dermal applications. Int J Nanomedicine, 2012. 7: p. 1841-50.

[9] Sutherland, R.M., Cell and environment interactions in tumor microregions: the multicell spheroid model. Science, 1988. 240(4849): p. 177-84.

[10] Minchinton, A.I. and I.F. Tannock, Drug penetration in solid tumours. Nat Rev Cancer, 2006. 6(8): p. 583-92.

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