Abstract

The present research work aimed to develop and characterize nanobubbles (NBs) for synergistic action in human cell line A549 using gefitinib and oxygen. NBs were prepared by loading oxygen in β-cyclodextrin-based inclusion complex (IC), whereas in nanosponges by polymer condensation method. Initially, the amino-functionalization was performed using (3-aminopropyl) triethoxysilane and then, underwent PEGylation to achieve site-specific action. The loading capacities of PEGylated and non-PEGylated NBs of gefitinib were found to be 85.11 ± 2.31% and 86.14±1.24%, respectively, whereas oxygen levels were found to be 2.8mg/L and 6.9mg/L, respectively. The synergistic effect of gefitinib NBs was observed by flow cytometry due to apoptosis of cell line A549 (with apoptotic rate ranged from 35.2±2.15% to 73.6±1.57%) by inhibiting EGFR pathway and further confirmed using western blotting technique. Dual delivery of gefitinib and oxygen from β-cyclodextrin-based nanosponges showed that NBs act as a novel therapy in the treatment of non-small cell lung cancer.

摘要

目前的研究工作旨在开发和表征纳米气泡 (NBs)，以使用吉非替尼和氧气在人类细胞系 A549 中发挥协同作用。NB是通过在基于β-环糊精的包合物（IC）中负载氧来制备的，而在纳米海绵中是通过聚合物缩合法制备的。最初，使用（3-氨基丙基）三乙氧基硅烷进行氨基官能化，然后进行聚乙二醇化以实现位点特异性作用。发现吉非替尼的聚乙二醇化和非聚乙二醇化 NB 的负载能力分别为 85.11±2.31% 和 86.14±1.24%，而氧水平分别为 2.8mg/L 和 6.9mg/L。流式细胞仪观察到吉非替尼 NBs 的协同作用是由于细胞系 A549 的凋亡（凋亡率范围为 35.2±2.15% 至 73.6±1. 57%）通过抑制 EGFR 通路并使用蛋白质印迹技术进一步证实。从基于β-环糊精的纳米海绵中双重递送吉非替尼和氧气表明，NB可作为治疗非小细胞肺癌的新疗法。