National Research Laboratory for Transporters Targeted Drug Design Research Institute of Pharmaceutical Sciences College of Pharmacy, Seoul National University, Seoul, 151-742, South Korea.
Pharm Res. 2012 Mar;29(3):795-805. doi: 10.1007/s11095-011-0603-6. Epub 2011 Oct 5.
To evaluate the usefulness of hematoporphyrin (HP)-modification of the surface of doxorubicin (DOX)-loaded bovine serum albumin (BSA) nanoparticles (NPs) in the liver cancer-selective delivery of DOX.
HP-modified NPs (HP-NPs) were prepared by conjugation of amino groups on the surface of NPs with HP, a ligand for low density lipoprotein (LDL) receptors on the hepatoma cells. In vitro cellular accumulation of DOX, in vivo biodistribution of DOX, safety, and anti-tumor efficacy were evaluated for HP-NPs.
Cytotoxicity and accumulation of DOX were in the order of HP-NPs>NPs>solution form (SOL). Cellular uptake from HP-NPs was proportional to the expression level of LDL receptors on the cells, indicating possible involvement of LDL receptor-mediated endocytosis (RME) in uptake. The "merit index," an AUC ratio of DOX in liver (target organ) to DOX in heart (major side effect organ) following iv administration of HP-NPs to hepatoma rats, was 132.5 and 4 times greater compared to SOL and NPs, respectively. The greatest suppression of body weight decrease and tumor size increase was observed for iv-administered HP-NPs in tumor-bearing mice.
HP modification appears to be useful in selective delivery of NP-loaded DOX to tumors.
评估血卟啉（HP）修饰阿霉素（DOX）载牛血清白蛋白（BSA）纳米颗粒（NPs）在肝癌选择性递药中的作用。
通过 NPs 表面的氨基与 HP 缀合，HP 是肝癌细胞低密度脂蛋白（LDL）受体的配体，从而制备 HP 修饰的 NPs（HP-NPs）。评估了 HP-NPs 的体内分布、安全性和抗肿瘤疗效。
DOX 的细胞毒性和积累顺序为 HP-NPs>NPs>溶液形式（SOL）。从 HP-NPs 的细胞摄取与细胞上 LDL 受体的表达水平成正比，表明摄取可能涉及 LDL 受体介导的内吞作用（RME）。与 SOL 和 NPs 相比，HP-NPs 静脉给药给肝癌大鼠后，DOX 在肝脏（靶器官）和心脏（主要副作用器官）的 AUC 比值（“优点指数”）分别增加了 132.5 倍和 4 倍。在荷瘤小鼠中，静脉给予 HP-NPs 可最大程度地抑制体重下降和肿瘤体积增加。
HP 修饰似乎可用于将载药 NP 递送至肿瘤的选择性递送。
