Resveratrol is a kind of phytoalexin produced in several plants with self-defense effect. It is known for its anti-inflammatory and ant-cancer effects. However, it has low efficacy due to its degradation before reaching the target. To heighten its delivery rate and efficacy, gold nanoparticles (GNPs) under 30 nm size were synthesized as drug carrier and conjugated with resveratrol via polyvinylpyrrolidone (PVP) as cross-linker. These gold nanoparticles conjugated with resveratrol (GRs) were used to estimate their anti-tumor effects through cell cycle arrest. It was found that resveratrol-and GRs-treated groups had decreased extent of G0/G1 phase but increased extent of S phase compared to control and GNP-treated groups, suggesting that the effect was due to resveratrol which was attached to gold nanoparticles. To estimate cytotoxicity after treatment with GNPs and GRs, the extent of lactate dehydrogenase (LDH) release was investigated. Results showed that GNPs and GRs-treated groups had almost no difference in LDH release compared to control group, suggesting that the extent of toxicity was not significant. Taken together, these results suggest that GRs could be potentially effective in treating cancer as anti-tumor drug with further development.
Background Pancreatic ductal adenocarcinoma (PDAC) remains one of the most fatal malignancies. Several chemotherapies employing fluorouracil (5-FU) and gemcitabine were attempted, but the survival rate was extremely low. Resveratrol (RVT), known as a polyphenol compound and phytoalexin, was demonstrated to induce intrinsic apoptosis in cancer cells. However, its low delivery performance and efficiency at tumor sites remain an obstacle to exploit RVT as a drug. To address these problems, we bio-conjugated resveratrol with gold nanoparticles (GNPs) via polyvinylpyrrolidone as a cross-linker (RVT@PVP-GNPs) and investigated whether the fabrications could enhance the delivery performance and anti-tumor efficacy of RVT. Results The fabrication of gold nanoparticles (GNPs) and bio-conjugated with resveratrol (RVT@PVP-GNPs) was conducted firstly. TEM image, spectrophotometry and zeta-potential revealed that the GNPs and RVT@PVP-GNPs having a size of approximately 40 nm were successfully synthesized and exhibited moderate stability. GNPs alone represented no damage in PANC-1 cells and moreover diminished the cytotoxicity of RVT in Raw264.7 murine macrophage cells, demonstrating the superiority of gold nanoparticles as a drug carrier. Evaluation using dialysis showed a burst release rate of RVT within 96 h at pH 5.0, demonstrating the possibility of enhanced efficiency of RVT delivery through blood vessels to the tumor. The RVT@PVP-GNPs induced increased rates of S-phase cell cycle arrest and apoptosis compared with free RVT. Notably, RVT@PVP-GNPs diminished the proportion of necrotic cells, whereas free RVT increased it. We also demonstrated that the RVT@PVP-GNPs may induce an apoptosis via intrinsic mitochondria with higher degree compared with free RVT, indicating the possibility of enhanced anti-tumor agents. In animal studies, RVT@PVP-GNPs conjugated with AS1411 aptamer induced efficient tumor volume suppression without accumulation in or damage to the kidneys in vivo. Conclusions The results demonstrate that RVT@PVP-GNPs enhance the anti-tumor efficacy of free RVT by activating the intrinsic apoptotic pathway and could be considered as potential anti-tumor drug candidates against pancreatic cancer cells.
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