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

Lung cancer is the most common type of cancer worldwide, accounting for 13% of all deaths annually. Survivors of this cancer nearly always live with the possibility of cancer recurrence. The objective of this research was to develop a drug-loaded nanoparticle that decreases the likelihood of lung cancer recurrence by preventing the reformation of lung tumors. Nanoparticle encapsulation has been shown to increase drug bioavailability, enhance tumor targeting for localized delivery, and allow for more sustained release of drugs compared to free drug administration. The nanoparticles used for this project were resveratrol-loaded acetalated dextran nanoparticles (RSV:Ac-Dex NPs). The NPs were formed using a single emulsion process, encapsulating the hydrophobic drug RSV inside the tunable degradable polymer Ac-Dex. These particles were characterized in terms of morphology, size and zeta potential, drug loading, in vitro drug release and degradation. Particles loaded with RSV showed successful encapsulation of the drug, with particle size ranging from 150 - 250 nm in diameter. Particles also demonstrated sustained release of drug at both pH 7.4 and pH 6.5 to represent release in normal physiological conditions and local tumor environment conditions, respectively. The efficacy of RSV in A549 lung adenocarcinoma cell line was evaluated in both two-dimensional (2D) and three-dimensional (3D) cell culture conditions. Dose-response curves from the drug applications was compared with the cellular response to application of the RSV:Ac-Dex NPs. The diameters of 3D lung cancer multicellular spheroids (MCS) were measured when RSV was applied either before or after MCS formation in order to compare the effects of RSV as a preventive or treatment drug. Cellular response in A549 cells exhibited significant cell death with concentrations of RSV ranging from 50 - 250 μM, and yielded significantly smaller or nonexistent MCS when RSV was applied before formation. The delivery of the actual NPs for in vitro cellular response tests will be performed for comparison to free drug application. Overall RSV:Ac-Dex NPs are expected to be a useful and efficient chemotherapy to prevent recurrence of lung tumors for cancer patients in remission.