Department of Chemical and Biological Engineering, American University of Sharjah, Sharjah, UAE.
Material Science and Engineering PhD Program, College of Arts and Sciences, American University of Sharjah, Sharjah, UAE.
Sci Rep. 2024 May 7;14(1):10499. doi: 10.1038/s41598-024-61278-x.
Improving the efficacy of chemotherapy remains a key challenge in cancer treatment, considering the low bioavailability, high cytotoxicity, and undesirable side effects of some clinical drugs. Targeted delivery and sustained release of therapeutic drugs to cancer cells can reduce the whole-body cytotoxicity of the agent and deliver a safe localized treatment to the patient. There is growing interest in herbal drugs, such as curcumin, which is highly noted as a promising anti-tumor drug, considering its wide range of bioactivities and therapeutic properties against various tumors. Conversely, the clinical efficacy of curcumin is limited because of poor oral bioavailability, low water solubility, instability in gastrointestinal fluids, and unsuitable pH stability. Drug-delivery colloid vehicles like liposomes and nanoparticles combined with microbubbles and ultrasound-mediated sustained release are currently being explored as effective delivery modes in such cases. This study aimed to synthesize and study the properties of curcumin liposomes (CLs) and optimize the high-frequency ultrasound release and uptake by a human breast cancer cell line (HCC 1954) through in vitro studies of culture viability and cytotoxicity. CLs were effectively prepared with particles sized at 81 ± 2 nm, demonstrating stability and controlled release of curcumin under ultrasound exposure. In vitro studies using HCC1954 cells, the combination of CLs, ultrasound, and Definity microbubbles significantly improved curcumin's anti-tumor effects, particularly under specific conditions: 15 s of continuous ultrasound at 0.12 W/cm power density with 0.6 × 10 microbubbles/mL. Furthermore, the study delved into curcumin liposomes' cytotoxic effects using an Annexin V/PI-based apoptosis assay. The treatment with CLs, particularly in conjunction with ultrasound and microbubbles, amplified cell apoptosis, mainly in the late apoptosis stage, which was attributed to heightened cellular uptake within cancer cells.
提高化疗疗效仍然是癌症治疗的一个关键挑战,因为一些临床药物的生物利用度低、细胞毒性高和副作用不理想。将治疗药物靶向递送到癌细胞并进行持续释放,可以降低药物的全身细胞毒性,并为患者提供安全的局部治疗。草药药物越来越受到关注,例如姜黄素,由于其广泛的生物活性和对各种肿瘤的治疗特性,被高度认为是一种有前途的抗肿瘤药物。然而,由于口服生物利用度差、水溶性低、在胃肠道液体中不稳定以及 pH 值稳定性不合适,姜黄素的临床疗效有限。目前,正在探索脂质体和纳米粒等药物输送胶体载体与微泡和超声介导的持续释放相结合,作为这种情况下的有效输送模式。本研究旨在合成姜黄素脂质体(CL)并研究其性质,并通过体外培养活力和细胞毒性研究优化高频超声释放和人乳腺癌细胞系(HCC1954)摄取。CL 有效地用粒径为 81±2nm 的粒子制备,在超声暴露下表现出姜黄素的稳定性和控制释放。体外研究使用 HCC1954 细胞,CL、超声和 Definity 微泡的组合显著提高了姜黄素的抗肿瘤效果,特别是在特定条件下:0.12W/cm 功率密度下连续超声 15s,微泡浓度为 0.6×10 微泡/ml。此外,本研究还使用 Annexin V/PI 基于的凋亡测定法研究了姜黄素脂质体的细胞毒性作用。CL 的治疗作用,特别是与超声和微泡联合使用,放大了细胞凋亡,主要在晚期凋亡阶段,这归因于癌细胞内摄取的增加。