Babunagappan Kaviya Vijayalakshmi, Seetharaman Abirami, Ariraman Subastri, Santhosh Poornima Budime, Genova Julia, Ulrih Natasa Poklar, Sudhakar Swathi
Department of Applied Mechanics and Biomedical Engineering, Indian Institute of Technology Madras Chennai India
Institute of Solid State Physics, Bulgarian Academy of Sciences Tzarigradsko Chausee Sofia Bulgaria.
Nanoscale Adv. 2024 Jan 2;6(8):2026-2037. doi: 10.1039/d3na00953j. eCollection 2024 Apr 16.
Breast cancer has a poor prognosis due to the toxic side effects associated with high doses of chemotherapy. Liposomal drug encapsulation has resulted in clinical success in enhancing chemotherapy tolerability. However, the formulation faces severe limitations with a lack of colloidal stability, reduced drug efficiency, and difficulties in storage conditions. Nanoarchaeosomes (NA) are a new generation of highly stable nanovesicles composed of the natural ether lipids extracted from archaea. In our study, we synthesized and characterized the NA, evaluated their colloidal stability, drug release potential, and anticancer efficacy. Transmission electron microscopy images have shown that the NA prepared from the hyperthermophilic archaeon K1 was in the size range of 61 ± 3 nm. The dynamic light scattering result has confirmed that the NA were stable at acidic pH (pH 4) and high temperature (70 °C). The NA exhibited excellent colloidal stability for 50 days with storage conditions at room temperature. The cell viability results have shown that the pure NA did not induce cytotoxicity in NIH 3T3 fibroblast cells and are biocompatible. Then NA were loaded with doxorubicin (NAD), and FTIR and UV-vis spectroscopy results have confirmed high drug loading efficiency of 97 ± 1% with sustained drug release for 48 h. The cytotoxicity studies in MCF-7 breast cancer cell lines showed that NAD induced cytotoxicity at less than 10 nM concentration. Fluorescence-activated cell sorting (FACS) results confirmed that NAD induced late apoptosis in nearly 92% of MCF-7 cells and necrosis in the remaining cells with cell cycle arrest at the G0/G1 phase. Our results confirmed that the NA could be a potential next-generation carrier with excellent stability, high drug loading efficiency, sustained drug release ability, and increased therapeutic efficacy, thus reducing the side effects of conventional drugs.
由于高剂量化疗带来的毒副作用,乳腺癌的预后较差。脂质体药物封装在提高化疗耐受性方面已取得临床成功。然而,该制剂面临着严重的局限性,如缺乏胶体稳定性、药物效率降低以及储存条件困难等问题。纳米古菌脂质体(NA)是由从古菌中提取的天然醚脂组成的新一代高度稳定的纳米囊泡。在我们的研究中,我们合成并表征了NA,评估了它们的胶体稳定性、药物释放潜力和抗癌功效。透射电子显微镜图像显示,由嗜热古菌K1制备的NA尺寸范围为61±3nm。动态光散射结果证实,NA在酸性pH(pH 4)和高温(70°C)下是稳定的。在室温储存条件下,NA表现出优异的胶体稳定性,长达50天。细胞活力结果表明,纯NA在NIH 3T3成纤维细胞中不诱导细胞毒性,具有生物相容性。然后将阿霉素(DOX)负载到NA中(NAD),傅里叶变换红外光谱(FTIR)和紫外可见光谱结果证实药物负载效率高达97±1%,药物持续释放48小时。对MCF-7乳腺癌细胞系的细胞毒性研究表明,NAD在浓度低于10 nM时诱导细胞毒性。荧光激活细胞分选(FACS)结果证实,NAD在近92%的MCF-7细胞中诱导晚期凋亡,其余细胞发生坏死,细胞周期停滞在G0/G1期。我们的结果证实,NA可能是一种潜在的下一代载体,具有优异的稳定性、高药物负载效率、持续药物释放能力和增强的治疗效果,从而减少传统药物的副作用。
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