Baskararaj Suraj, Panneerselvam Theivendren, Govindaraj Saravanan, Arunachalam Sankarganesh, Parasuraman Pavadai, Pandian Sureshbabu Ram Kumar, Sankaranarayanan Murugesan, Mohan Uma Priya, Palanisamy Ponnusamy, Ravishankar Vigneshwaran, Kunjiappan Selvaraj
1Department of Biotechnology, Kalasalingam Academy of Research and Education, Krishnankoil, Virudhunagar, Tamilnadu 626126 India.
Department of Pharmaceutical Chemistry, Saraswathi College of Pharmacy, NH-24, Anwarpur, Pilkhuwa, Hapur, Uttar Pradesh 245304 India.
3 Biotech. 2020 Mar;10(3):136. doi: 10.1007/s13205-020-2132-7. Epub 2020 Feb 24.
This study aimed to formulate and characterize the folate receptor-targeted PEGylated liposome encapsulating bioactive compounds from to enhance the anticancer activity. Twenty valued bioactive compounds (3-hydroxy benzoicacid, gallicacid, chlorogenicacid, cinnamicacid, artemiseole, hydrazine carbothioamide, etc.,) are confirmed from methanol extract of using analytical techniques like HPLC and GC-MS. The delivery of bioactive compounds of via naturally overexpressed folate receptor (FR) to FR-positive breast cancer cells was studied. FR targeted PEGylated liposome was constructed by modified thin-film hydration technique using FA-PEG-DSPE/cholesterol/DSPC (5:40:55) and bioactive compounds of was encapsulated. Their morphology, size, shape, physiological stability and drug release kinetics were studied. The study reports of extract-encapsulated PEGylated liposome showed spherical shaped particles with amorphous in nature. The mean diameter of extract-encapsulated PEGylated and FA-conjugated PEGylated liposomes was found to be 110 ± 6 nm and 140 ± 5 nm, respectively. Based on the stability studies, it could be confirmed that FA-conjugated PEGylated liposome was highly stable in various physiological buffer medium. FA-conjugated PEGylated liposome can steadily release the bioactive compounds of extract in acidic medium (pH 5.4). MTT assay demonstrated the concentration-dependent cytotoxicity against MCF-7 cells after 24 h with IC of 81 µg/mL. Also, PEGylated liposome enhanced the delivery of extract in MCF-7 cells. After treatment, typical apoptotic morphology of condensed nuclei and distorted membrane bodies was picturized. Additionally, PEGylated liposome targets the mitochondria of MCF-7 cells and significantly increased the level of ROS and contributes to the damage of mitochondrial transmembrane potential. Hence, PEGylated liposome could positively deliver the bioactive compounds of extract into FR-positive breast cancer cells (MCF-7) and exhibit great potential in anticancer therapy.
本研究旨在制备并表征包封来自[具体来源未提及]生物活性化合物的叶酸受体靶向聚乙二醇化脂质体，以增强其抗癌活性。利用高效液相色谱（HPLC）和气相色谱 - 质谱联用（GC - MS）等分析技术，从[具体来源未提及]的甲醇提取物中确认了20种有价值的生物活性化合物（3 - 羟基苯甲酸、没食子酸、绿原酸、肉桂酸、青蒿醚、肼基硫代酰胺等）。研究了通过天然过度表达的叶酸受体（FR）将[具体来源未提及]的生物活性化合物递送至FR阳性乳腺癌细胞的情况。采用FA - PEG - DSPE/胆固醇/DSPC（5:40:55）通过改良薄膜水化技术构建FR靶向聚乙二醇化脂质体，并包封[具体来源未提及]的生物活性化合物。研究了它们的形态、大小、形状、生理稳定性和药物释放动力学。关于包封[具体来源未提及]提取物的聚乙二醇化脂质体的研究报告显示，颗粒呈球形，本质上为无定形。发现包封[具体来源未提及]提取物的聚乙二醇化脂质体和FA缀合的聚乙二醇化脂质体的平均直径分别为110±6 nm和140±5 nm。基于稳定性研究，可以确认FA缀合的聚乙二醇化脂质体在各种生理缓冲介质中高度稳定。FA缀合的聚乙二醇化脂质体可以在酸性介质（pH 5.4）中稳定释放[具体来源未提及]提取物的生物活性化合物。MTT法显示，24小时后对MCF - 7细胞具有浓度依赖性细胞毒性，半数抑制浓度（IC）为81μg/mL。此外，聚乙二醇化脂质体增强了[具体来源未提及]提取物在MCF - 7细胞中的递送。处理后，呈现出典型的凋亡形态，细胞核浓缩，膜体变形。此外，聚乙二醇化脂质体靶向MCF - 7细胞的线粒体，显著提高活性氧（ROS）水平，并导致线粒体跨膜电位受损。因此，聚乙二醇化脂质体可以将[具体来源未提及]提取物的生物活性化合物有效地递送至FR阳性乳腺癌细胞（MCF - 7），在抗癌治疗中展现出巨大潜力。
