Borges Sandro da Silva, Miranda Sued Eustáquio Mendes, Marinho Victor Hugo de Souza, Barros André Luís Branco de, Yoshioka Sergio, Hage-Melim Lorane Izabel da Silva, Silva Ana Carolina de Jesus, Ferreira Irlon Maciel, Oliveira Anna Eliza Maciel de Faria Mota
Biocatalysis and Applied Organic Synthesis Laboratory, Federal University of Amapá, University Campus Marco Zero do Equador, Rodovia Josmar Chaves Pinto, Km 02, Macapá 68902-280, AP, Brazil.
Department of Clinical and Toxicological Analyses, Federal University of Minas Gerais, Avenida Antonio Carlos, 6627, Belo Horizonte 31270-901, MG, Brazil.
Molecules. 2025 Aug 11;30(16):3337. doi: 10.3390/molecules30163337.
Breast cancer, a highly prevalent malignancy among women, continues to pose a significant global health challenge, as conventional therapies are often limited by adverse effects. This study developed and evaluated nanostructured lipid carriers (NLCs) encapsulating fatty acid amides (FAAs) semi-synthesized from andiroba oil and combined with silk fibroin (SF) as a novel therapeutic strategy. Methods: FAAs were synthesized via direct amidation and characterized by GC-MS, FT-IR, and C NMR. These fatty acid amides were then incorporated into NLCs containing SF. The formulation was evaluated for its physicochemical stability, cell selectivity, and cytotoxicity against 4T1 murine breast cancer cells and healthy human fibroblasts. Results: The NLC-FAA/SF formulation exhibited physicochemical stability (average particle size: 136.9 ± 23.6 nm; zeta potential: -8.3 ± 12.0 mV; polydispersity index: 0.19 ± 0.04), indicating a monodisperse and stable system. In vitro cytotoxicity assays demonstrated high selective activity against 4T1 murine breast cancer cells (IC = 0.18 ± 0.06 μg/mL) and negligible toxicity to healthy human fibroblasts. Molecular docking studies revealed favorable interactions between the FAAs and cannabinoid receptors CB1 and CB2, with unsaturated FAAs showing higher binding scores and stability, suggesting their potential as cannabinoid receptor ligands. These findings highlight NLC-FAA/SF as a promising, selective, and effective nanoplatform for breast cancer treatment, warranting further investigation into its mechanism of action and in vivo efficacy.
乳腺癌是女性中一种高度流行的恶性肿瘤，由于传统疗法常常受到副作用的限制，它仍然是一项重大的全球健康挑战。本研究开发并评估了纳米结构脂质载体（NLCs），其包裹了从巴西香脂树油半合成的脂肪酸酰胺（FAAs），并与丝素蛋白（SF）结合，作为一种新型治疗策略。方法：通过直接酰胺化合成FAAs，并通过气相色谱 - 质谱联用仪（GC-MS）、傅里叶变换红外光谱仪（FT-IR）和碳核磁共振仪（C NMR）进行表征。然后将这些脂肪酸酰胺掺入含有SF的NLCs中。对该制剂进行了物理化学稳定性、细胞选择性以及对4T1小鼠乳腺癌细胞和健康人成纤维细胞的细胞毒性评估。结果：NLC-FAA/SF制剂表现出物理化学稳定性（平均粒径：136.9 ± 23.6 nm；zeta电位：-8.3 ± 12.0 mV；多分散指数：0.19 ± 0.04），表明是一个单分散且稳定的系统。体外细胞毒性试验表明对4T1小鼠乳腺癌细胞具有高选择性活性（IC = 0.18 ± 0.06 μg/mL），而对健康人成纤维细胞的毒性可忽略不计。分子对接研究揭示了FAAs与大麻素受体CB1和CB2之间的良好相互作用，不饱和FAAs显示出更高的结合分数和稳定性，表明它们作为大麻素受体配体的潜力。这些发现突出了NLC-FAA/SF作为一种有前景、选择性且有效的乳腺癌治疗纳米平台，值得进一步研究其作用机制和体内疗效。
