Department of Chemical Engineering, Faculty of Chemistry, University of Murcia (UMU), Campus de Espinardo, Murcia 30100, Spain.
School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, U.K.
Mol Pharm. 2024 Jun 3;21(6):2781-2794. doi: 10.1021/acs.molpharmaceut.3c01186. Epub 2024 Apr 27.
The nanocrystal (NC) technology has become one of the most commonly used strategies for the formulation of poorly soluble actives. Given their large specific surface, NCs are mainly used to enhance the oral absorption of poorly soluble actives. Differently from conventional nanoparticles, which require the use of carrier materials and have limited drug loadings, NCs' drug loading approaches 100% since they are formed of the pure drug and surrounded by a thin layer of a stabilizer. In this work, we report the covalent decoration of curcumin NCs with folic acid (FA) using EDC/NHS chemistry and explore the novel systems as highly loaded "Trojan horses" to target cancer cells. The decorated NCs demonstrated a remarkable improvement in curcumin uptake, exhibiting enhanced growth inhibition in cancer cells (HeLa and MCF7) while sparing healthy cells (J774A.1). Cellular uptake studies revealed significantly heightened entry of FA-decorated NCs into cancer cells compared to unmodified NCs while also showing reduced uptake by macrophages, indicating a potential for prolonged circulation . These findings underline the potential of NC highly loaded nanovectors for drug delivery and, in particular, for cancer therapies, effectively targeting folate receptor-overexpressing cells while evading interception by macrophages, thus preserving their viability and offering a promising avenue for precise and effective treatments.
纳米晶体（NC）技术已成为将难溶性活性物质配方化的最常用策略之一。鉴于其较大的比表面积，NC 主要用于增强难溶性活性物质的口服吸收。与需要使用载体材料且药物载药量有限的传统纳米颗粒不同，NC 的药物载药量接近 100%，因为它们由纯药物形成并被一层薄薄的稳定剂包围。在这项工作中，我们报告了使用 EDC/NHS 化学将叶酸（FA）共价修饰到姜黄素 NC 上，并探索了新型系统作为高载量的“特洛伊木马”来靶向癌细胞。与未修饰的 NC 相比，修饰的 NC 显示出姜黄素摄取的显著改善，对癌细胞（HeLa 和 MCF7）表现出增强的生长抑制作用，同时对健康细胞（J774A.1）具有保护作用。细胞摄取研究表明，FA 修饰的 NC 进入癌细胞的能力明显增强，而巨噬细胞的摄取减少，表明其具有延长循环的潜力。这些发现强调了高载量纳米载体用于药物输送的潜力，特别是用于癌症治疗，能够有效靶向叶酸受体过表达细胞，同时逃避巨噬细胞的拦截，从而保持其活力，并为精确有效的治疗提供有前途的途径。
