PDF(Pubmed)
Abstract：
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 in vivo. 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.
摘要：
纳米晶体（NC）技术已成为配制难溶性活性物质的最常用策略之一。鉴于它们的大比表面，NCs主要用于增强难溶性活性物质的口服吸收。不同于传统的纳米粒子，这需要使用载体材料和有限的药物负载，NCs的载药量接近100%,因为它们是由纯药物形成的,并且被稳定剂的薄层包围。在这项工作中,我们报告了使用EDC/NHS化学对姜黄素NC与叶酸（FA）的共价修饰，并探索了新型系统作为高负荷的“特洛伊木马”靶向癌细胞。装饰的NC表现出姜黄素吸收的显着改善，在癌细胞（HeLa和MCF7）中表现出增强的生长抑制，同时保留健康细胞（J774A.1）。细胞摄取研究显示，与未修饰的NC相比，FA修饰的NC进入癌细胞显着增加，同时也显示巨噬细胞的摄取减少。表明体内循环延长的可能性。这些发现强调了NC高负荷纳米载体用于药物递送的潜力，特别是,癌症治疗，有效靶向叶酸受体过表达细胞，同时避免巨噬细胞的拦截，从而保持它们的生存能力，并为精确和有效的治疗提供有希望的途径。
