Department of Pharmaceutics, College of Pharmacy, Najran University, Najran, Saudi Arabia.
Department of Pharmacognosy, Tishk International University, Erbil, Iraq.
Expert Opin Drug Deliv. 2024 Feb;21(2):229-244. doi: 10.1080/17425247.2024.2317194. Epub 2024 Feb 28.
Triple-negative breast cancer (TNBC) presents unique challenges in diagnosis and treatment. Resveratrol exhibits potential as a therapeutic intervention against TNBC by regulating various pathways such as the PI3K/AKT, RAS/RAF/ERK, PKCδ, and AMPK, leading to apoptosis through ROS-mediated CHOP activationand the expression of DR4 and DR5. However, the clinical efficacy of resveratrol is limited due to its poor biopharmaceutical characteristics and low bioavailability at the tumor site. Nanotechnology offers a promising approach to improving the biopharmaceutical characteristics of resveratrol to achieve clinical efficacy in different cancers. The small dimension (<200 nm) of nanotechnology-mediated drug delivery system is helpful to improve the bioavailability, internalization into the TNBC cell, ligand-specific targeted delivery of loaded resveratrol to tumor site including reversal of MDR (multi-drug resistance) condition.
This manuscript provides a comprehensive discussion on the structure-activity relationship (SAR), underlying anticancer mechanism, evidence of anticancer activity in in-vitro/in-vivo investigations, and the significance of nanotechnology-mediated delivery of resveratrol in TNBC.
Advanced nano-formulations of resveratrol such as oxidized mesoporous carbon nanoparticles, macrophage-derived vesicular system, functionalized gold nanoparticles, etc. have increased the accumulation of loaded therapeutics at the tumor-site, and avoid off-target drug release. In conclusion, nano-resveratrol as a strategy may provide improved tumor-specific image-guided treatment options for TNBC utilizing theranostic approach.
三阴性乳腺癌(TNBC)在诊断和治疗方面带来了独特的挑战。白藜芦醇通过调节 PI3K/AKT、RAS/RAF/ERK、PKCδ 和 AMPK 等多种途径,表现出作为治疗 TNBC 的潜在干预作用,导致通过 ROS 介导的 CHOP 激活和 DR4 和 DR5 的表达而发生细胞凋亡。然而,由于其较差的生物制药特性和在肿瘤部位的低生物利用度,白藜芦醇的临床疗效受到限制。纳米技术为改善白藜芦醇的生物制药特性以实现不同癌症的临床疗效提供了一种很有前途的方法。纳米技术介导的药物递送系统的小尺寸(<200nm)有助于提高生物利用度、将白藜芦醇内化进入 TNBC 细胞、将负载的白藜芦醇通过配体特异性靶向递送至肿瘤部位,包括逆转多药耐药(MDR)状态。
本文全面讨论了结构-活性关系(SAR)、潜在的抗癌机制、体外/体内研究中抗癌活性的证据,以及纳米技术介导的白藜芦醇在 TNBC 中的递送的意义。
白藜芦醇的先进纳米制剂,如氧化介孔碳纳米粒子、巨噬细胞衍生囊泡系统、功能化金纳米粒子等,增加了负载治疗剂在肿瘤部位的积累,并避免了脱靶药物释放。总之,纳米白藜芦醇作为一种策略,可能为 TNBC 提供了改进的肿瘤特异性图像引导治疗选择,利用治疗策略。