International Centre for Genetic Engineering & Biotechnology, New Delhi 110067, India.
Nanomedicine (Lond). 2013 Dec;8(12):1927-42. doi: 10.2217/nnm.12.201. Epub 2013 Feb 12.
Different nanoparticles have been investigated to deliver chemotherapeutic agents, but complex synthesis procedures and biocompatibility issues raise concerns in developing them for safe human usage. The aim of this work is to develop α,β-dehydrophenylalanine-containing, self-assembled, amphipathic dipeptide nanoparticles for tumor-targeted drug delivery and therapy.
MATERIAL & METHODS: Solution-phase peptide synthesis was used to synthesize dipeptides. Nanoparticles were prepared by molecular self-assembly. A tumor distribution study was carried out using a radiolabeling method. Tumor regression studies were carried out in murine ascitic tumors in BALB/c mice and breast tumor xenografts in in nonobese diabetic/severe combined immunodeficiency mice.
Arg-α,β-dehydrophenylalanine formed self-assembled nanoparticles that could be easily derivatized with folic acid. Folic acid-derivatized nanoparticles showed enhanced cellular uptake and, when loaded with doxorubicin, showed enhanced tumor regression compared with underivatized nanoparticles or native drug, without any adverse side effects, both in vitro and in vivo.
不同的纳米颗粒已被用于递送化疗药物，但复杂的合成程序和生物相容性问题引起了人们对将其开发用于安全的人体应用的关注。本研究旨在开发含有α，β-脱水苯丙氨酸的、自组装的、两亲性二肽纳米颗粒，用于肿瘤靶向药物传递和治疗。
采用溶液相肽合成法合成二肽。通过分子自组装制备纳米颗粒。采用放射性标记法进行肿瘤分布研究。在 BALB/c 小鼠的腹水肿瘤和非肥胖型糖尿病/严重联合免疫缺陷小鼠的乳腺癌异种移植模型中进行肿瘤消退研究。
Arg-α，β-脱水苯丙氨酸形成了自组装纳米颗粒，可轻松与叶酸进行衍生化。叶酸衍生化的纳米颗粒显示出增强的细胞摄取，并且当负载多柔比星时，与未衍生化的纳米颗粒或天然药物相比，显示出增强的肿瘤消退作用，而没有任何不良反应，无论是在体外还是体内。
