Angelopoulou Athina, Papachristodoulou Myria, Voulgari Efstathia, Mouikis Andreas, Zygouri Panagiota, Gournis Dimitrios P, Avgoustakis Konstantinos
Department of Pharmacy, Medical School, University of Patras, 26504 Patras, Greece.
Department of Materials Science and Engineering, University of Ioannina, 45110 Ioannina, Greece.
Pharmaceutics. 2024 Nov 14;16(11):1452. doi: 10.3390/pharmaceutics16111452.
: Graphene Oxide (GO) has shown great potential in biomedical applications for cancer therapeutics. The biosafety and stability issues of GO in biological media have been addressed by functionalization with polyethylene glycol (PEG). : In this work, carboxylated, nanosized GO (nCGO) was evaluated as a potential carrier of paclitaxel (PCT). The effect of PEG characteristics on particle size and surface charge, colloidal stability, drug, and release, and the hemolytic potential of nCGO, was investigated. Optimum PEG-nCGO/PCT formulations based on the above properties were evaluated for their anticancer activity (cytotoxicity and apoptosis induction) in the A549 lung cancer cell line. : An increase in the length of linear PEG chains and the use of branched (4-arm) instead of linear PEG resulted in a decrease in hydrodynamic diameter and an increase in ζ potential of the pegylated nCGO particles. Pegylated nCGO exhibited high colloidal stability in phosphate-buffered saline and in cell culture media and low hemolytic effect, even at a relatively high concentration of 1 mg/mL. The molecular weight of PEG and branching adversely affected PCT loading. An increased rate of PCT release at an acidic pH of 6.0 compared to the physiological pH of 7.4 was observed with all types of pegylated nCGO/PCT. Pegylated nCGO exhibited lower cytotoxicity and apoptotic activity than non-pegylated nCGO. Cellular uptake of pegylated nCGO increased with incubation time with cells leading to increased cytotoxicity of PEG-nCGO/PCT with incubation time, which became higher than that of free PCT at 24 and 48 h of incubation. : The increased biocompatibility of the pegylated nCGO and the enhanced anticancer activity of PEG-nCGO/PCT compared to free PCT are desirable properties with regard to the potential clinical application of PEG-nCGO/PCT as an anticancer nanomedicine.
氧化石墨烯（GO）在癌症治疗的生物医学应用中已显示出巨大潜力。通过用聚乙二醇（PEG）进行功能化处理，解决了GO在生物介质中的生物安全性和稳定性问题。在本研究中，对羧基化纳米级GO（nCGO）作为紫杉醇（PCT）的潜在载体进行了评估。研究了PEG特性对粒径和表面电荷、胶体稳定性、药物及释放以及nCGO溶血潜力的影响。基于上述特性，评估了最佳PEG-nCGO/PCT制剂在A549肺癌细胞系中的抗癌活性（细胞毒性和凋亡诱导）。线性PEG链长度的增加以及使用支链（四臂）而非线性PEG导致聚乙二醇化nCGO颗粒的流体动力学直径减小和ζ电位增加。聚乙二醇化nCGO在磷酸盐缓冲盐水和细胞培养基中表现出高胶体稳定性且溶血作用低，即使在相对较高浓度1mg/mL时也是如此。PEG的分子量和支化对PCT负载有不利影响。与生理pH值7.4相比，在酸性pH值6.0时，所有类型的聚乙二醇化nCGO/PCT的PCT释放速率均增加。聚乙二醇化nCGO比未聚乙二醇化的nCGO表现出更低的细胞毒性和凋亡活性。聚乙二醇化nCGO的细胞摄取随与细胞孵育时间的增加而增加，导致PEG-nCGO/PCT的细胞毒性随孵育时间增加而增加，并在孵育24和48小时时高于游离PCT。就PEG-nCGO/PCT作为抗癌纳米药物的潜在临床应用而言，聚乙二醇化nCGO生物相容性的提高以及PEG-nCGO/PCT与游离PCT相比增强的抗癌活性是理想的特性。
