Meiyi Liang1,2, Mingyan Guo1,3, Phei Er Saw1,4, Yandan Yao1,2,5. 1. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People's Republic of China. 2. Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People's Republic of China. 3. Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People's Republic of China. 4. Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People's Republic of China. 5. Shenshan Medical Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Shanwei, 516621, People's Republic of China.
Abstract
Introduction: Chemotherapeutics are known to have undesirable side effects (i.e. nausea, weight loss, hair loss, weakened immune system, etc.) due to the non-specificity of the drugs. Encapsulation of these chemotherapeutics inside nanoparticles significantly improves the bioavailability and half-life of drugs, while increasing their tumor penetration and localization. However, most, if not all, nanoparticles in clinics or research are synthetic, with no long-term studies on the effect of these nanoparticles in vivo. Herein, we developed a synergistic resveratrol nanoparticle system by using lecithin encapsulation. Lecithin, being a fully natural phospholipid derived from soybean, possesses inherent anti-tumor activity. Methods: Lec(RSV) was successfully prepared using the nanoprecipitation method, and characterized by particle size and zeta potential analysis, and transmission electron microscopy (TEM). The in vitro cellular uptake and cytotoxic effects of Lec(RSV) were investigated in human breast cancer cell line BT474. Finally, the in vivo tumoral uptake of Lec(RSV) was carried out in the BT474 orthotopic model. Results: Lec(RSV) showed a uniform distribution of ~120 nm, with prolonged stability. Lec(RSV) showed high cellular uptake and anti-cancer properties in vitro. Time-dependent uptake in the BT474 xenograft model indicated an increased tumoral uptake and apoptosis rate at 4 hours after tail vein injection of Lec(RSV). Conclusion: Taken together, we successfully developed a fully natural Lec(RSV) that possesses potent anti-cancer activity in vitro, with good tumoral uptake in vivo. We hypothesize that Lec(RSV) could be a safe anti-cancer therapeutic that could be easily translated into clinical application.
Introduction: Chemotherapeutics are known to have undesirable side effects (i.e. nausea, weight loss, hair loss, weakened immune system, etc.) due to the non-specificity of the drugs. Encapsulation of these chemotherapeutics inside nanoparticles significantly improves the bioavailability and half-life of drugs, while increasing their tumor penetration and localization. However, most, if not all, nanoparticles in clinics or research are synthetic, with no long-term studies on the effect of these nanoparticles in vivo. Herein, we developed a synergistic resveratrol nanoparticle system by using lecithin encapsulation. Lecithin, being a fully natural phospholipid derived from soybean, possesses inherent anti-tumor activity. Methods: Lec(RSV) was successfully prepared using the nanoprecipitation method, and characterized by particle size and zeta potential analysis, and transmission electron microscopy (TEM). The in vitro cellular uptake and cytotoxic effects of Lec(RSV) were investigated in human breast cancer cell line BT474. Finally, the in vivo tumoral uptake of Lec(RSV) was carried out in the BT474 orthotopic model. Results: Lec(RSV) showed a uniform distribution of ~120 nm, with prolonged stability. Lec(RSV) showed high cellular uptake and anti-cancer properties in vitro. Time-dependent uptake in the BT474 xenograft model indicated an increased tumoral uptake and apoptosis rate at 4 hours after tail vein injection of Lec(RSV). Conclusion: Taken together, we successfully developed a fully natural Lec(RSV) that possesses potent anti-cancer activity in vitro, with good tumoral uptake in vivo. We hypothesize that Lec(RSV) could be a safe anti-cancer therapeutic that could be easily translated into clinical application.