El-Deeb Ibrahim M, Pittala Valeria, Eltayeb Diab, Greish Khaled
Department of Medical Sciences, Royal College of Surgeons in Ireland, Medical University of Bahrain, Busaiteen 228, Bahrain.
Department of Drug and Health Science, University of Catania, 95125 Catania, Italy.
Molecules. 2021 Jun 9;26(12):3532. doi: 10.3390/molecules26123532.
Triple-negative breast cancer (TNBC) is a heterogeneous subtype of tumors that tests negative for estrogen receptors, progesterone receptors, and excess HER2 protein. The mainstay of treatment remains chemotherapy, but the therapeutic outcome remains inadequate. This paper investigates the potential of a duocarmycin derivative, tafuramycin A (TFA), as a new and more effective chemotherapy agent in TNBC treatment. To this extent, we optimized the chemical synthesis of TFA, and we encapsulated TFA in a micellar system to reduce side effects and increase tumor accumulation. In vitro and in vivo studies suggest that both TFA and SMA-TFA possess high anticancer effects in TNBC models. Finally, the encapsulation of TFA offered a preferential avenue to tumor accumulation by increasing its concentration at the tumor tissues by around four times in comparison with the free drug. Overall, the results provide a new potential strategy useful for TNBC treatment.
三阴性乳腺癌(TNBC)是一种异质性肿瘤亚型,其雌激素受体、孕激素受体及过量HER2蛋白检测均为阴性。治疗的主要手段仍然是化疗,但治疗效果仍不尽人意。本文研究了一种双环霉素衍生物塔夫拉霉素A(TFA)作为一种新型且更有效的化疗药物用于TNBC治疗的潜力。在此范围内,我们优化了TFA的化学合成,并将TFA包裹于胶束系统中以减少副作用并增加肿瘤蓄积。体外和体内研究表明,TFA和SMA-TFA在TNBC模型中均具有高抗癌作用。最后,与游离药物相比,TFA的包裹通过将其在肿瘤组织中的浓度提高约四倍,为肿瘤蓄积提供了一条优先途径。总体而言,这些结果为TNBC治疗提供了一种新的潜在策略。