Abstract：
OBJECTIVE: Folate receptor expression increase up to 30% in breast cancer cells and could be used as a possible ligand to couple to folate-functionalized nanoparticles. Metformin (Met) is an anti-hyperglycemic agent whose anti-cancer properties have been formerly reported. Consequently, in the current study, we aimed to synthesize and characterize folate-functionalized PLGA-PEG NPs loaded with Met and evaluate the anti-cancer effect against the MDA-MB-231 human breast cancer cell line.
METHODS: FA-PLGA-PEG NPs were synthesized by employing the W1/O/W2 technique and their physicochemical features were evaluated by FE-SEM, TEM, FTIR, and DLS methods. The cytotoxic effects of free and Nano-encapsulated drugs were analyzed by the MTT technique. Furthermore, RT-PCR technique was employed to assess the expression levels of apoptotic and anti-apoptotic genes.
RESULTS: MTT result indicated Met-loaded FA-PLGA-PEG NPs exhibited cytotoxic effects in a dose-dependently manner and had more cytotoxic effects relative to other groups. The remarkable down-regulation (hTERT and Bcl-2) and up-regulation (Caspase7, Caspase3, Bax, and p53) gene expression were shown in treated MDA-MB-231 cells with Met-loaded FA-PLGA-PEG NPs.
CONCLUSIONS: Folate-Functionalized PLGA-PEG Nanoparticles are suggested as an appropriate approach to elevate the anticancer properties of Met for improving the treatment effectiveness of breast cancer cells.
METHODS: FA-PLGA-PEG NPs were synthesized by employing the W1/O/W2 technique and their physicochemical features were evaluated by FE-SEM, TEM, FTIR, and DLS methods. The cytotoxic effects of free and Nano-encapsulated drugs were analyzed by the MTT technique. Furthermore, RT-PCR technique was employed to assess the expression levels of apoptotic and anti-apoptotic genes.
RESULTS: MTT result indicated Met-loaded FA-PLGA-PEG NPs exhibited cytotoxic effects in a dose-dependently manner and had more cytotoxic effects relative to other groups. The remarkable down-regulation (hTERT and Bcl-2) and up-regulation (Caspase7, Caspase3, Bax, and p53) gene expression were shown in treated MDA-MB-231 cells with Met-loaded FA-PLGA-PEG NPs.
CONCLUSIONS: Folate-Functionalized PLGA-PEG Nanoparticles are suggested as an appropriate approach to elevate the anticancer properties of Met for improving the treatment effectiveness of breast cancer cells.
摘要：
目的：叶酸受体在乳腺癌细胞中的表达增加高达30％，可以用作偶联叶酸功能化纳米颗粒的可能配体。二甲双胍(Met)是一种抗高血糖剂,其抗癌性质先前已有报道。因此,在目前的研究中，我们旨在合成和表征负载有Met的叶酸功能化的PLGA-PEGNP，并评估对MDA-MB-231人乳腺癌细胞系的抗癌作用。
方法：采用W1/O/W2技术合成FA-PLGA-PEGNP，并通过FE-SEM评估其理化特性，TEM,FTIR,和DLS方法。通过MTT技术分析了游离和纳米包封药物的细胞毒性作用。此外，采用RT-PCR技术评估凋亡和抗凋亡基因的表达水平。
结果:MTT结果表明负载Met的FA-PLGA-PEGNP以剂量依赖性方式表现出细胞毒性作用,并且相对于其他组具有更多的细胞毒性作用。显着下调（hTERT和Bcl-2）和上调（Caspase7，Caspase3，Bax，和p53）基因表达在用Met负载的FA-PLGA-PEGNP处理的MDA-MB-231细胞中显示。
结论：叶酸官能化的PLGA-PEG纳米粒被认为是提高Met抗癌特性以提高乳腺癌细胞治疗效果的合适方法。
方法：采用W1/O/W2技术合成FA-PLGA-PEGNP，并通过FE-SEM评估其理化特性，TEM,FTIR,和DLS方法。通过MTT技术分析了游离和纳米包封药物的细胞毒性作用。此外，采用RT-PCR技术评估凋亡和抗凋亡基因的表达水平。
结果:MTT结果表明负载Met的FA-PLGA-PEGNP以剂量依赖性方式表现出细胞毒性作用,并且相对于其他组具有更多的细胞毒性作用。显着下调（hTERT和Bcl-2）和上调（Caspase7，Caspase3，Bax，和p53）基因表达在用Met负载的FA-PLGA-PEGNP处理的MDA-MB-231细胞中显示。
结论：叶酸官能化的PLGA-PEG纳米粒被认为是提高Met抗癌特性以提高乳腺癌细胞治疗效果的合适方法。
