Kunjiappan Selvaraj, Panneerselvam Theivendren, Somasundaram Balasubramanian, Sankaranarayanan Murugesan, Parasuraman Pavadai, Joshi Shrinivas D, Arunachalam Sankarganesh, Murugan Indhumathy
Sir CV Raman-KS Krishnan International Research Center, Kalasalingam University, Krishnankoil-626126, India.
Department of Pharmaceutical Chemistry, Karavali College of Pharmacy, Vamanjoor, Mangalore-575028, Karnataka, India.
Anticancer Agents Med Chem. 2018;18(13):1900-1918. doi: 10.2174/1871520618666180628155223.
To investigate N-succinyl chitosan nanoparticles (NSC NPs) encapsulation with biomass for high utilization enhanced effectiveness and least side effects for anticancer activity.
The potential bioactive compounds from D. bardawil biomass were encapsulated NSC NPs by ionotropic gelation method and to characterize its molecular shape, particle size, stability and polydispersity index using FTIR, XRD, SEM, TEM and Zetasize Nano analyzer. Signaling pathway analysis, molecular docking study and in vitro anticancer screening were performed on chosen H-RasP21, 721P and liver cancer cell lines (HepG2), respectively.
The biomass majorly contains 6 bioactive compounds such as β-carotene, lutein, zeaxanthin, phytoene, canthaxanthin, and phytofluene were identified by LC-MS. The biomass encapsulated NSC NPs showed an average particle size of 80±5.6 nm in spherical shape, crystalline nature, zeta potential of -32±2.7 mV and polydispersity index of 0.51±0.02. Interestingly, the identified target using graph theoretical signaling pathway analysis and molecular docking study showed strong interaction of NSC NPs in binding pockets of H-RasP21 protooncogene. At 50μg/mL, NPs displayed 95.60% cytotoxicity in HepG2 cell line. The apoptotic cell cycle analysis showed cell death for 24 h and 48 h representing 13.13% and 47.04%, respectively.
The highly cross-linked, biocompatible, biodegradable, nontoxic NSC NPs promising carrier for delivery of bioactive molecules present in the biomass was found to be actively involved in deregulation of cellular growth in targeted cancer cells. Thus active NPs serve as a novel nanodrug to enhance the controlled; site specific drug delivery in the management of cancer.
研究用生物质包裹N-琥珀酰壳聚糖纳米颗粒（NSC NPs），以实现高利用率、增强疗效并使抗癌活性的副作用最小化。
采用离子凝胶法将来自杜氏盐藻生物质的潜在生物活性化合物包裹在NSC NPs中，并使用傅里叶变换红外光谱（FTIR）、X射线衍射（XRD）、扫描电子显微镜（SEM）、透射电子显微镜（TEM）和Zetasize纳米分析仪对其分子形状、粒径、稳定性和多分散指数进行表征。分别对选定的H-RasP21、721P和肝癌细胞系（HepG2）进行信号通路分析、分子对接研究和体外抗癌筛选。
通过液相色谱-质谱联用（LC-MS）鉴定出该生物质主要含有6种生物活性化合物，如β-胡萝卜素、叶黄素、玉米黄质、八氢番茄红素、角黄素和六氢番茄红素。包裹了生物质的NSC NPs呈球形，平均粒径为80±5.6 nm，具有晶体性质，zeta电位为-32±2.7 mV，多分散指数为0.51±0.02。有趣的是，使用图论信号通路分析和分子对接研究确定的靶点显示，NSC NPs在H-RasP21原癌基因的结合口袋中有很强的相互作用。在50μg/mL时，纳米颗粒在HepG2细胞系中显示出95.60%的细胞毒性。凋亡细胞周期分析显示，24小时和48小时的细胞死亡率分别为13.13%和47.04%。
高度交联、生物相容、可生物降解、无毒的NSC NPs有望成为一种载体，用于递送生物质中存在的生物活性分子，被发现积极参与靶向癌细胞中细胞生长的失调。因此，活性纳米颗粒可作为一种新型纳米药物，以增强癌症治疗中药物的可控性和位点特异性递送。
