Abdel-Rafei Mohamed K, Askar Moustafa A, Azab Khaled S, El-Sayyad Gharieb S, El Kodous Mohamed Abd, El Fatih Neama M, Tawill Ghada El, Thabet Noura M
Radiation Biology Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority, Cairo 11787, Egypt.
Drug Radiation Research Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority, Cairo 11787, Egypt.
Curr Cancer Drug Targets. 2023;23(2):118-144. doi: 10.2174/1568009622666220816123508.
Breast cancer (BC) has a complex and heterogeneous etiology, and the emergence of resistance to conventional chemo-and radiotherapy results in unsatisfactory outcomes during BC treatment. Targeted nanomedicines have tremendous therapeutic potential in BC treatment over their free drug counterparts.
Hence, this study aimed to evaluate the newly fabricated pH-sensitive multifunctional FAHA- Amygdalin@FeO nano-core-shell composite (AF nanocomposite) and/or γ-radiation for effective localized BC therapy.
The physicochemical properties of nanoparticles were examined, including stability, selectivity, responsive release to pH, cellular uptake, and anticancer efficacy. MCF-7 and MDA-MB-231 cells were treated with AF at the determined IC doses and/or exposed to γ-irradiation (RT) or were kept untreated as controls. The antitumor efficacy of AF was proposed via assessing anti-proliferative effects, cell cycle distribution, apoptosis, and determination of the oncogenic effectors.
In a bio-relevant medium, AF nanoparticles demonstrated extended-release characteristics that were amenable to acidic pH and showed apparent selectivity towards BC cells. The bioassays revealed that the HA and FA-functionalized AF markedly hindered cancer cell growth and enhanced radiotherapy (RT) through inducing cell cycle arrest (pre-G1 and G2/M) and increasing apoptosis, as well as reducing the tumorigenicity of BCs by inhibiting Silent information regulation factor 1 (SIRT1) and restoring p53 expression, deactivating the Yes-associated protein (YAP)/ Transcriptional coactivator with PDZ-binding motif (TAZ) signaling axis, and interfering with the tumor growth factor- β(TGF- β)/SMAD3 and HIF-1α/VEGF signaling hub while up-regulating SMAD7 protein expression.
Collectively, the novel AF alone or prior RT abrogated BC tumorigenicity.
乳腺癌（BC）具有复杂且异质的病因，对传统化疗和放疗产生耐药性导致BC治疗效果不尽人意。靶向纳米药物在BC治疗中比游离药物具有巨大的治疗潜力。
因此，本研究旨在评估新制备的pH敏感多功能FAHA-苦杏仁苷@FeO纳米核壳复合材料（AF纳米复合材料）和/或γ射线用于有效的局部BC治疗。
检测纳米颗粒的物理化学性质，包括稳定性、选择性、对pH的响应释放、细胞摄取和抗癌效果。MCF-7和MDA-MB-231细胞用确定的IC剂量的AF处理和/或暴露于γ射线（放疗），或不进行处理作为对照。通过评估抗增殖作用、细胞周期分布、凋亡以及确定致癌效应因子来提出AF的抗肿瘤效果。
在生物相关介质中，AF纳米颗粒表现出适合酸性pH的缓释特性，并对BC细胞表现出明显的选择性。生物测定表明，HA和FA功能化的AF通过诱导细胞周期停滞（G1期前和G2/M期）和增加凋亡，以及通过抑制沉默信息调节因子1（SIRT1）和恢复p53表达、失活Yes相关蛋白（YAP）/含PDZ结合基序的转录共激活因子（TAZ）信号轴、干扰肿瘤生长因子-β（TGF-β）/SMAD3和HIF-1α/VEGF信号枢纽同时上调SMAD7蛋白表达，显著抑制癌细胞生长并增强放疗（RT）。
总体而言，新型AF单独使用或放疗前使用均可消除BC的致瘤性。
