Standley Stephany M, Kwon Young Jik, Murthy Niren, Kunisawa Jun, Shastri Nilabh, Guillaudeu Steven J, Lau Lana, Fréchet Jean M J
Center for New Directions in Organic Synthesis and Departments of Chemistry and Molecular and Cellular Biology, University of California, Berkeley, California 94720-1460, USA.
Bioconjug Chem. 2004 Nov-Dec;15(6):1281-8. doi: 10.1021/bc049956f.
Acid-degradable protein-loaded polymer particles show promise for antigen-based vaccines due to their ability to activate cytotoxic T lymphocytes (CTLs) in vitro. Protein loadings and cytotoxic T lymphocyte activation efficiencies have now been enhanced through novel delivery vehicle designs. In particular, the use of a more hydrophilic acid-degradable cross-linker leads to increased water dispersibility and increased protein loading efficiency for the particles. A 2.5-fold increase in protein encapsulation allows the delivery of more protein antigen to antigen presenting cells (APCs) leading to a 20-fold rise in antigen presentation levels. The mechanism by which APCs internalize these particles was explored using the phagocytosis inhibitor, cytochalasin B. In addition, preliminary in vivo experiments were conducted to investigate the ability of the protein-loaded particles to provide immunity against tumors in mice, and an enhanced survival rate over the use of protein alone was observed, indicating that this vaccine delivery strategy has great practical potential.
由于酸可降解的载蛋白聚合物颗粒能够在体外激活细胞毒性T淋巴细胞（CTL），因此在基于抗原的疫苗方面显示出前景。目前，通过新型递送载体设计提高了蛋白质负载量和细胞毒性T淋巴细胞激活效率。特别地，使用更具亲水性的酸可降解交联剂可提高颗粒的水分散性和蛋白质负载效率。蛋白质包封率提高2.5倍，使得更多的蛋白质抗原能够递送至抗原呈递细胞（APC），从而使抗原呈递水平提高20倍。使用吞噬作用抑制剂细胞松弛素B探索了APC内化这些颗粒的机制。此外，还进行了初步的体内实验，以研究载蛋白颗粒在小鼠体内提供抗肿瘤免疫力的能力，结果观察到与单独使用蛋白质相比存活率有所提高，这表明这种疫苗递送策略具有巨大的实际潜力。
