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新型宫颈癌靶向和氧化还原响应蜂毒素缀合物的研制与药学研究。

Development and pharmaceutical investigation of novel cervical cancer-targeting and redox-responsive melittin conjugates.

机构信息

Department of Medical Biotechnology, Institute of Health Sciences, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey.

Department of Biomedical Engineering, Graduate School of Natural and Applied Sciences, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey.

出版信息

Sci Rep. 2023 Oct 25;13(1):18225. doi: 10.1038/s41598-023-45537-x.

Abstract

Cervical cancer has recently become one of the most prevalent cancers among women throughout the world. Traditional cancer therapies generate side effects due to off-target toxicity. Thus, novel cancer medications coupled with suitable drug delivery systems are required to improve cancer therapies. Melittin peptide has a high affinity to disrupt cancer cells. In this study, we designed targeted and redox-responsive Melittin conjugates for cervical cancer and then tested them in vitro. Folic acid and squamous cell carcinoma-specific peptide (CKQNLAEG) were used as targeting agents to design various conjugates. Our findings indicate that both anticancer conjugates were effective against different cancer cell lines, including MCF-7, C33A, and HeLa. Moreover, these conjugates were found to have antioxidant and antibacterial effects as well as reduced hemolytic activity. The CM-Target (N-terminus cysteine modified-Melittin-targeting peptide-functionalized conjugate) has become more stable and acted specifically against squamous cell carcinoma, whereas folic acid (FA)-containing conjugates acted efficiently against all cancer types studied, especially for breast cancer. According to our results, these anticancer conjugates may be possible anticancer drug candidates that have fewer adverse effects.

摘要

宫颈癌最近已成为全世界女性中最常见的癌症之一。传统的癌症疗法由于靶向毒性而产生副作用。因此,需要新型癌症药物与合适的药物输送系统相结合,以改善癌症治疗。蜂毒素肽对破坏癌细胞具有很高的亲和力。在这项研究中,我们设计了针对宫颈癌的靶向和氧化还原响应性蜂毒素缀合物,并在体外进行了测试。叶酸和鳞状细胞癌特异性肽(CKQNLAEG)被用作靶向剂来设计各种缀合物。我们的研究结果表明,两种抗癌缀合物都对不同的癌细胞系有效,包括 MCF-7、C33A 和 HeLa。此外,这些缀合物具有抗氧化和抗菌作用,并且溶血活性降低。CM-Target(N 末端半胱氨酸修饰的蜂毒素靶向肽功能化缀合物)变得更加稳定,并且专门针对鳞状细胞癌起作用,而含有叶酸(FA)的缀合物则有效地针对所有研究的癌症类型起作用,尤其是乳腺癌。根据我们的结果,这些抗癌缀合物可能是具有较少不良反应的潜在抗癌药物候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5c9/10600185/e2cacc3e2910/41598_2023_45537_Fig1_HTML.jpg

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