Singh Amit, Bora Shivangi, Kumar Pankaj, Kukreti Ritushree, Kaushik Mahima
Nano-bioconjugate Chemistry Lab, Cluster Innovation Centre, University of Delhi, Delhi 110007, India.
Department of Chemistry, University of Delhi, Delhi 110007, India.
ACS Omega. 2024 Dec 20;10(1):170-180. doi: 10.1021/acsomega.4c02983. eCollection 2025 Jan 14.
Liver cancer is a prevalent and significant cause of death in humans. The use of novel biodegradable materials for various biomedical applications is being recently recommended as complementary as well as alternative solution for traditional chemotherapy. This study focuses on the synthesis of biodegradable nanocarriers [chitosan-coated poly(lactic acid) NPs (Cht-PLA NPs)] for the delivery of an anticancer drug vinblastine (Vbx) and to evaluate its therapeutic potential in human hepatocellular carcinoma (HepG2) cells. The Cht-PLA NPs were synthesized using the nanoprecipitation method and characterized by transmission electron microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy, dynamic light scattering, and zeta potential techniques. The results showed that the nanoparticle sizes are in the range of 100-200 nm with positive surface charge. The release profile of the synthesized nanoformulation showed controlled release of the Vbx drug for 72 h. The anticancer efficacy of the synthesized nanoformulation was assessed on the HepG2 cell lines. The cytotoxicity study revealed that the Vbx-loaded Cht-PLA NPs showed higher toxicity with an increase in concentration as compared to the Vbx alone. Additionally, an cellular uptake study revealed higher internalization as compared to the drug alone due to the chitosan coating. Further, the ability to stimulate the reactive oxygen species (ROS) generation and variation in mitochondrial membrane potential at the IC concentration of Vbx-loaded Cht-PLA NPs was confirmed by using 2,7-dichlorodihydrofluorescein diacetate and rhodamine 123 dyes, respectively, and were analyzed under fluorescence microscopy. Hence, the results showed that Vbx-loaded Cht-PLA NPs possess high anticancer activity due to its higher cellular toxicity, cellular uptake, increased ROS production, and disruption in mitochondrial membrane potential. All these properties of the synthesized nanoformulation suggest it's potential applications in drug delivery systems, targeting liver cancer.
肝癌是人类中普遍且重要的死亡原因。最近，新型可生物降解材料在各种生物医学应用中的使用被推荐为传统化疗的补充和替代解决方案。本研究聚焦于合成用于递送抗癌药物长春碱（Vbx）的可生物降解纳米载体[壳聚糖包被的聚乳酸纳米颗粒（Cht-PLA NPs）]，并评估其在人肝癌（HepG2）细胞中的治疗潜力。采用纳米沉淀法合成Cht-PLA NPs，并通过透射电子显微镜、扫描电子显微镜、傅里叶变换红外光谱、动态光散射和zeta电位技术对其进行表征。结果表明，纳米颗粒尺寸在100-200nm范围内，表面带正电荷。合成的纳米制剂的释放曲线显示Vbx药物可控制释放72小时。在HepG2细胞系上评估了合成纳米制剂的抗癌功效。细胞毒性研究表明，与单独的Vbx相比，负载Vbx的Cht-PLA NPs随着浓度增加显示出更高的毒性。此外，细胞摄取研究表明，由于壳聚糖包被，与单独的药物相比具有更高的内化作用。此外，分别使用2,7-二氯二氢荧光素二乙酸酯和罗丹明123染料证实了在负载Vbx的Cht-PLA NPs的IC浓度下刺激活性氧（ROS）生成能力和线粒体膜电位变化，并在荧光显微镜下进行分析。因此，结果表明负载Vbx的Cht-PLA NPs由于其更高的细胞毒性、细胞摄取、增加的ROS产生和线粒体膜电位破坏而具有高抗癌活性。合成纳米制剂的所有这些特性表明其在药物递送系统中靶向肝癌的潜在应用。
