A novel nanoformulation of parthenolide coated with polydopamine shows selective cytotoxicity and induces apoptosis in gastric cancer cells

Parisa Karimian Ensaf, Mohammad Taghi Goodarzi, Masoud Homayouni Tabrizi, Ali Neamati, Samira Sadat Hosseinyzadeh
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Abstract

An anticancer agent derived from a natural product, parthenolide (PN), was studied to formulate PN into poly(lactic-co-glycolic acid) (PLGA). Polydopamine (PDA) was employed to modify the surface of PN-PLGA. Following characterization, the PN-PLGA-PDA was evaluated for its in vitro release, cytotoxicity, and ability to induce apoptosis using flow cytometry and real-time quantitative PCR. According to the present study, PN-PLGA-PDA had a size of 195.5 nm which is acceptable for efficient enhanced permeation and retention (EPR) performance. The SEM results confirmed the size and spherical shape of the nanoparticles. The percentage of encapsulation efficiency was 96.9%. The zeta potential of PN-PLGA-PDA was − 31.8 mV which was suitable for its stability. FTIR spectra of the PN-PLGA-PDA indicated the chemical stability of the PN due to intermolecular hydrogen bonds between polymer and drug. The release of PN from PN-PLGA-PDA in PBS (pH 7.4) was only 20% during the first 48 h and less than 40% during 144 h. PN-PLGA-PDA exhibited anticancer properties in a dose-dependent manner that was more cytotoxic against cancer cells than normal cells. Moreover, real-time qPCR results indicated that the formulation activated apoptosis genes to exert its cytotoxic effect and activate the NF-kB pathway. Based on our findings, PN-PLGA-PDA could serve as a potential treatment for cancer.

Abstract Image

涂有聚多巴胺的新型帕芬内酯纳米制剂显示出选择性细胞毒性并诱导胃癌细胞凋亡
研究人员研究了一种从天然产物偏苯内酯(PN)中提取的抗癌剂,并将 PN 配制成聚(乳酸-共聚乙醇酸)(PLGA)。聚多巴胺(PDA)被用来修饰 PN-PLGA 的表面。表征后,使用流式细胞术和实时定量 PCR 评估了 PN-PLGA-PDA 的体外释放、细胞毒性和诱导细胞凋亡的能力。根据本研究,PN-PLGA-PDA 的尺寸为 195.5 nm,这对于高效的增强渗透和保留(EPR)性能来说是可以接受的。扫描电镜结果证实了纳米颗粒的尺寸和球形。封装效率为 96.9%。PN-PLGA-PDA 的 zeta 电位为 - 31.8 mV,适合其稳定性。PN-PLGA-PDA 的傅立叶变换红外光谱表明,由于聚合物和药物之间存在分子间氢键,PN 具有化学稳定性。在 PBS(pH 7.4)中,PN-PLGA-PDA 在最初 48 小时内的 PN 释放率仅为 20%,144 小时内的释放率低于 40%。PN-PLGA-PDA 具有抗癌特性,其抗癌作用呈剂量依赖性,对癌细胞的细胞毒性高于正常细胞。此外,实时 qPCR 结果表明,该制剂可激活凋亡基因,从而发挥细胞毒性作用,并激活 NF-kB 通路。根据我们的研究结果,PN-PLGA-PDA 可作为一种潜在的癌症治疗方法。
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