Zakaria Muhammad Nizam Zulfi, Rosyidah A'liyatur, Wulandari Diah Anggraini, Ritmaleni Ritmaleni, Sahid Muhammad Novrizal Abdi, Rifa'i Muhaimin, Muttaqien Sjaikhurrizal El, Setyawati Damai Ria, Sekaringtyas Fransiska Christydira, Dimyati Arbi, Hamzah Amir, Pratiwi Riyona Desvy
Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University, Malang, Indonesia.
Research Center for Vaccine and Drugs, National Research and Innovation Agency (BRIN), Research Organization for Health, Bogor, Indonesia.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Aug 23. doi: 10.1007/s00210-025-04533-w.
Breast cancer remains highly prevalent due to its complex etiology. Curcumin, a natural compound with therapeutic potential, faces physicochemical limitations, leading to the development of its synthetic analog, pentagamavunon-6 (PGV-6). However, PGV-6's low aqueous solubility limits its efficacy, necessitating nanoliposome-based encapsulation to enhance its effectiveness. This study is aimed at synthesizing, characterizing, and evaluating the antioxidant and anticancer properties of PGV-6-loaded nanoliposome (NLP). The NLPs were fabricated using the thin film hydration technique which composed of LPC, cholesterol, Tween-80, and PGV-6 (28:4.3:7.8:1). The particle characterization was conducted by measuring particle size, polydispersity index (PDI), and zeta potential using PSA and observing their morphology using SEM and HR-TEM. Antioxidant activity was assessed using ABTS assay, while anticancer effects were evaluated through cytotoxicity, apoptosis, lysosomal uptake, ROS generation, and cell cycle assays on MCF-7 breast cancer cells. The NLP formed spherical nanoparticles with a mean particle size of 127.7 ± 1.75 nm, PDI of 0.2 ± 0.03, and zeta potential of - 7.8 ± 0.64 mV. The NLP enhanced the antioxidant activity of PGV-6 by 15.4-fold (IC 3.24 ppm) compared to free PGV-6 (IC 49.93 ppm). Additionally, the cytotoxicity of NLP against cancer cells was 2.6 times stronger (IC 9.75 ppm) than free PGV-6 (IC 25.40 ppm). Mechanistically, free PGV-6 induced apoptosis by inhibiting the cell cycle at the G2/M phase, whereas NLP triggered apoptosis through an intrinsic mechanism, not only via mitochondrial pathway but also by targeting lysosomes to elevate intracellular ROS production and initiate the caspase cascade via the lysosomal pathway. These findings demonstrate that nanoliposome encapsulation improves the therapeutic potential of PGV-6, supporting its promise as a more effective antioxidant and anticancer agent.
由于其复杂的病因，乳腺癌仍然非常普遍。姜黄素是一种具有治疗潜力的天然化合物，但面临物理化学方面的限制，因此开发了其合成类似物五伽马武农 -6（PGV-6）。然而，PGV-6的低水溶性限制了其疗效，因此需要基于纳米脂质体的封装来提高其有效性。本研究旨在合成、表征和评估负载PGV-6的纳米脂质体（NLP）的抗氧化和抗癌特性。使用由LPC、胆固醇、吐温-80和PGV-6（28:4.3:7.8:1）组成的薄膜水化技术制备NLP。通过使用PSA测量粒径、多分散指数（PDI）和zeta电位，并使用SEM和HR-TEM观察其形态来进行颗粒表征。使用ABTS测定法评估抗氧化活性，同时通过对MCF-7乳腺癌细胞进行细胞毒性、凋亡、溶酶体摄取、ROS生成和细胞周期测定来评估抗癌效果。NLP形成了平均粒径为127.7±1.75nm、PDI为0.2±0.03且zeta电位为-7.8±0.64mV的球形纳米颗粒。与游离PGV-6（IC50为49.93ppm）相比，NLP将PGV-6的抗氧化活性提高了15.4倍（IC50为3.24ppm）。此外，NLP对癌细胞的细胞毒性比游离PGV-6（IC50为25.40ppm）强2.6倍（IC50为9.75ppm）。从机制上讲，游离PGV-6通过在G2/M期抑制细胞周期来诱导凋亡，而NLP通过内在机制触发凋亡，不仅通过线粒体途径，还通过靶向溶酶体来提高细胞内ROS产生并通过溶酶体途径启动半胱天冬酶级联反应。这些发现表明，纳米脂质体封装提高了PGV-6的治疗潜力，支持其作为一种更有效的抗氧化和抗癌剂的前景。
