这项研究通过利用阳离子抗菌肽(CAMPs)和细胞穿透肽(CPPs)的独特特性,探索了抗肿瘤剂5-FU在癌细胞中的有效性。传统的抗癌疗法面临很大的局限性,包括不利的药代动力学特征和对肿瘤部位的特异性不足。这些缺点通常需要更高的治疗剂剂量,导致正常细胞的严重毒性和不良副作用。肽已经成为靶向药物递送的有希望的载体,具有选择性地将治疗剂递送到表达特定受体的细胞的能力。这增强了细胞内药物递送,最大限度地减少耐药性,并降低毒性。在这项研究中,我们全面评估ADMET(吸收,分布,新陈代谢,排泄,和毒性)各种AMP和CPPs的特性,以深入了解其作为抗癌剂的潜力。肽合成涉及使用Liberty微波肽合成仪的固相合成。通过LC-MS和HPLC方法确认肽纯度。对于ADMET筛选,采用了计算工具,评估吸收等参数,分布,新陈代谢,排泄,和毒性。培养细胞系A549和UM-UC-5并用5-FU处理,凸轮,和CPPs。使用MTT测定法测量细胞活力。理化性质分析揭示了良好的药物相似性属性。这些肽对CYP3A4表现出潜在的抑制活性。ADMET预测表明可变的吸收和分布特征。此外,我们评估了这些肽单独和与5-FU组合的有效性,一种广泛使用的抗肿瘤剂,在两种不同的癌细胞系中,UM-UC-5和A549。我们的发现表明,CAMPs可以显着降低A549细胞的细胞活力,而CPPs在UM-UC-5细胞中表现出有希望的结果。了解这些多方面的影响可以为抗病毒和抗癌研究开辟新的途径。Further,实验验证是必要的,以确认这些肽的作用机制,特别是与5-FU结合使用。
This study explores the effectiveness of the antineoplastic agent 5-FU in cancer cells by leveraging the unique properties of cationic antimicrobial peptides (CAMPs) and cell-penetrating peptides (CPPs). Traditional anticancer therapies face substantial limitations, including unfavorable pharmacokinetic profiles and inadequate specificity for tumor sites. These drawbacks often necessitate higher therapeutic agent doses, leading to severe toxicity in normal cells and adverse side effects. Peptides have emerged as promising carriers for targeted drug delivery, with their ability to selectively deliver therapeutics to cells expressing specific receptors. This enhances intracellular drug delivery, minimizes drug resistance, and reduces toxicity. In this research, we comprehensively evaluate the ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties of various AMPs and CPPs to gain insights into their potential as anticancer agents. The peptide synthesis involved a solid-phase synthesis using a Liberty Microwave Peptide Synthesizer. The peptide purity was confirmed via LC-MS and HPLC methods. For the ADMET screening, computational tools were employed, assessing parameters like absorption, distribution, metabolism, excretion, and toxicity. The cell lines A549 and UM-UC-5 were cultured and treated with 5-FU, CAMPs, and CPPs. The cell viability was measured using the MTT assay. The physicochemical properties analysis revealed favorable drug-likeness attributes. The peptides exhibited potential inhibitory activity against CYP3A4. The ADMET predictions indicated variable absorption and distribution characteristics. Furthermore, we assessed the effectiveness of these peptides alone and in combination with 5-FU, a widely used antineoplastic agent, in two distinct cancer cell lines, UM-UC-5 and A549. Our findings indicate that CAMPs can significantly reduce the cell viability in A549 cells, while CPPs exhibit promising results in UM-UC-5 cells. Understanding these multifaceted effects could open new avenues for antiviral and anticancer research. Further, experimental validation is necessary to confirm the mechanism of action of these peptides, especially in combination with 5-FU.