Abstract

Lung cancer is one of the most widely recognised types of cancer and the acquisition of resistance towards chemotherapeutic drugs worsens the situation. Therefore, a site-directed, multi-targeting drug delivery system that is compliant with patients is the need of the hour. 5-Fluorouracil (5-FU), an anti-cancer chemotherapy drug, was delivered to the lung cancer cells using papain-inspired gold nanoparticles (PpGNPs) as the drug delivery system. Papain is anti-cancer by nature; hence, it rendered this anti-cancer property to the PpGNPs as well. This bio-conjugation of 5-FU and PpGNPs worked synergistically and more efficiently in combating lung cancer. The synthesis, stability, and the size of the PpGNPs, and their bio-conjugation with 5-FU (5F-PpGNPs), were confirmed by different physical techniques: for example, UV-Vis spectroscopy, TEM, DLS, and estimation of the zeta potential. The drug-loading efficiency of 5-FU in 5F-PpGNPs was confirmed and validated by UV-Vis spectroscopy. The efficacy of 5F-PpGNPs (IC₅₀ 11.7 µg/mL) against human lung cancer A549 cell line was found to have improved significantly over that of pure 5-FU (IC₅₀ 25.6 µg/mL). However, the 5F-PpGNPs did not show any significant toxicity (even up to a fairly high concentration) towards normal mouse embryonic fibroblasts cell line (3T3-L1). The apoptotic effects, nuclear condensation, ROS generation, and the loss of mitochondrial membrane potential (ΔΨm) of 5F-PpGNPs were analysed. The results clearly showed that conjugation with papain-inspired gold nanoparticles (5F-PpGNPs) significantly augmented the potency of 5-FU by acting synergistically. Thus, the enhanced anti-proliferating effect of 5F-PpGNPs over that of the pure drug would be an important step that will help to overcome the resistance of chemotherapeutic drugs towards lung cancer cells and prove to be of great advantage during lung cancer treatment.

摘要

肺癌是最广泛公认的癌症类型之一，对化学治疗药物的耐药性使情况恶化。因此，一个小时的需要是一个与患者相适应的定点，多目标药物输送系统。使用木瓜蛋白酶激发的金纳米颗粒（PpGNPs）作为药物递送系统，将抗氟化学药物5-氟尿嘧啶（5-FU）递送至肺癌细胞。木瓜蛋白酶具有抗癌作用。因此，它也赋予了PpGNPs这种抗癌特性。5-FU和PpGNP的这种生物结合在对抗肺癌中协同有效地发挥了作用。PpGNPs的合成，稳定性和大小，以及它们与5-FU（5F-PpGNPs）的生物缀合，已通过不同的物理技术得到了证实：例如，UV-Vis光谱，TEM，DLS，和ζ电位的估计。通过5-Vis光谱确认并验证了5-FU在5F-PpGNPs中的载药效率。5F-PpGNPs（IC的功效₅₀抗人肺癌A549细胞株11.7 µg / mL）比纯5-FU（IC _50）显着改善25.6 µg / mL）。但是，5F-PpGNP对正常小鼠胚胎成纤维细胞系（3T3-L1）没有显示出任何明显的毒性（甚至达到相当高的浓度）。分析了5F-PpGNPs的凋亡效应，核凝聚，ROS生成和线粒体膜电位（ΔΨm）的损失。结果清楚地表明，与木瓜蛋白酶启发的金纳米颗粒（5F-PpGNPs）结合可通过协同作用显着增强5-FU的效力。因此，与纯药物相比，5F-PpGNPs的增强的抗增殖作用将是重要的步骤，将有助于克服化学治疗药物对肺癌细胞的耐药性，并证明在肺癌治疗期间具有很大的优势。