(201i) Evaluation of the Cancer-Preventive Effect of Resveratrol-Loaded Nanoparticles on the Formation of Lung Tumor Spheroids

Despite the recent advancements in the treatment of cancer, it remains an enormous challenge for scientists. It is estimated in the U.S. that 1,688,780 new cases of cancer will be diagnosed in 2017 and 600,920 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 drugs for cancer prevention, such as: Tamoxifen for breast cancer and the human papilloma virus (HPV) vaccine for cervical intraepithelial neoplasia. More than 200 other chemopreventive agents are 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 vitroassays. Also, RSV-loaded gel nanoparticles enhanced intracellular uptake and cytotoxicity in a NCI-H460 lung cancer cell line [7], RSV loaded into nanostructure lipid carriers (NLC) exhibit higher penetration into the skin in comparison to solid lipid nanoparticles (SLN) [8], demonstrating improvement with RSV in nanoparticle systems.

The aim of this project was to evaluate the chemopreventive effect of RSV and RSV nanoparticles (NP) on the formation of tumor spheroids. We synthesized biodegradable nanoparticles comprised of acetalated dextran (Ac-Dex) loaded with RSV in order to increase the availability of the agent, 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]. So far, RSV 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.

Keywords: Resveratrol nanoparticles, chemoprevention, multicellular spheroids, lung cancer, acetalated dextran

 References

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