Evolva SA, Duggingerstrasse 23, 4153 Reinach, Switzerland.
J Control Release. 2018 Oct 10;287:216-234. doi: 10.1016/j.jconrel.2018.08.030. Epub 2018 Aug 25.
Lactobionic acid (LBA) has rapidly emerged as a strategic functionalization molecule in the development of nanoparticle-based platforms and biomaterials with promising therapeutic applications. Exploiting the multi-functionality of LBA has enabled to expand the drug loading, release and selective cellular uptake capacity of hepatoma-targeting chemotherapy and nanoparticle-based theranostic systems. The high liver-specificity displayed by LBA-conjugated dendrimers, micelles and nanoparticles has indeed reinforced the great potential of LBA in fine-tuning the surface engineering of promising drug carriers to combat hepatocellular carcinoma. Additionally, its cytocompatibility, selectivity and functionality confer unique properties to design synthetically engineered matrices with enhanced liver-specificity for liver tissue engineering applications. Notably, the biospecific identification and biochemical cross-linking specificity found with the asialoglycoprotein receptor (ASGPR) have converted LBA into the perfect cell-targeting ligand for strengthening the recognition between novel designed nanocarriers and hepatocytes at cellular level. The present review overviews the latest advances in the galactosylation of target-specific nanocarriers and polymers via LBA functionalization with an emphasis on the great bioengineering versatility offered by this polyhydroxy bionic acid in the preparation of next-generation tools ranging from contrast imaging agents to galactosylated scaffolds for the diagnosis and treatment of hepatic diseases. Perspectives on the bioengineering approaches that can foster the design of multi-functional LBA-conjugated therapeutic nanoplatforms are also discussed.
乳醛酸(LBA)作为一种具有战略意义的功能化分子,在基于纳米粒子的平台和具有有前途的治疗应用的生物材料的开发中迅速崭露头角。利用 LBA 的多功能性,可以扩展肝癌靶向化疗和基于纳米粒子的治疗诊断系统的药物负载、释放和选择性细胞摄取能力。LBA 缀合的树枝状大分子、胶束和纳米粒子表现出的高肝特异性,确实增强了 LBA 在微调有前途的药物载体的表面工程以对抗肝细胞癌方面的巨大潜力。此外,其细胞相容性、选择性和功能为设计具有增强的肝特异性的合成工程基质赋予了独特的特性,用于肝组织工程应用。值得注意的是,与天门冬氨酸糖蛋白受体(ASGPR)的生物特异性识别和生化交联特异性相结合,使 LBA 转化为理想的细胞靶向配体,可增强新型设计的纳米载体与肝细胞之间在细胞水平上的识别。本综述概述了通过 LBA 功能化对靶向特异性纳米载体和聚合物进行半乳糖基化的最新进展,重点介绍了这种多羟基仿生酸在制备下一代工具方面提供的巨大生物工程多功能性,这些工具的范围从对比成像剂到半乳糖化支架,用于诊断和治疗肝脏疾病。还讨论了可以促进多功能 LBA 缀合治疗性纳米平台设计的生物工程方法的观点。