文獻：Novel DSPE-PEG-Cholic Acid-Modified Liposomes with Hepatic Targeting Properties Improve the Anti-Tumor Efficacy of Oral Doxorubicin Hydrochloride for Liver Tumor-Bearing Mice

DOI: https://doi.org/10.1166/jbn.2017.2382

作者: Li, Ying; Yang, Dandan; Zhang, Yun; Zhu, Chunyan

摘要：

DSPE-PEG-cholic acid-modified liposomes (functional liposomes) with hepatic targeting via oral administration properties were explored for the loading of DOX·HCl. DSPE-PEG-cholic acid-modified DOX·HCl liposomes (functional DOX·HCl liposomes) were developed as an oral therapy that targets hepatic cancers. Subsequently, the effects of liposome formulations were investigated using in vitro HepG2 cell uptake assays, in vivo intestine distribution and targeting efficacy experiments in orthotopic HepG2 nude mice xenograft tumors and subcutaneous H22 mice xenograft tumors. Functional DOX·HCl liposomes of approximately 100 nm in diameter significantly increased the intracellular uptake of DOX·HCl, revealing strong inhibitory effects on HepG2 cells. Moreover, orally administered functional DOX·HCl liposomes demonstrated stronger antitumor efficacy than DOX·HCl and DOX·HCl liposomes in orthotopic HepG2 xenograft mice, but similar antitumor efficacy to DOX·HCl liposomes in subcutaneous H22 xenograft mice. In further analyses, cardiac and kidney toxicities were significantly reduced after orally administering functional DOX·HCl liposome formulations. The present data indicate that the oral administration of functional DOX·HCl liposomes increases hepatic targeting, provides superior efficacy of suppressing xenograft tumor, and overcomes limited cardiac and kidney toxicity.

探索了通過口服給藥具有肝靶向性的DSPE-PEG-膽酸修飾脂質體（功能性脂質體）負載DOX·HCl的特性。開發(fā)了DSPE-PEG-膽酸修飾的DOX·HCl脂質體（功能性DOX·HCl-脂質體）作為靶向肝癌的口服療法。

隨后，使用體外HepG2細胞攝取試驗、體內腸道分布和原位HepG2裸鼠異種移植腫瘤和皮下H22小鼠異種移植腫瘤的靶向療效實驗研究了脂質體制劑的影響。直徑約為100 nm的功能性DOX·HCl脂質體顯著增加了DOX·HCI的細胞內攝取，對HepG2細胞顯示出強烈的抑制作用。

此外，在原位HepG2異種移植物小鼠中，口服功能性DOX·HCl脂質體比DOX·HCI和DOX·HCl脂質體具有更強的抗腫瘤作用，但在皮下H22異種移植物鼠中，其抗腫瘤作用與DOX·鹽酸脂質體相似。在進一步的分析中，口服功能性DOX·HCl脂質體制劑后，心臟和腎臟毒性顯著降低。目前的數(shù)據(jù)表明，口服功能性DOX·HCl脂質體可增加肝靶向性，提供抑制異種移植物腫瘤的優(yōu)越療效，并克服有限的心臟和腎臟毒性。

相關推薦：

DSPE-PEG-FITC

DSPE-PEG-Folate

DSPE-PEG-IA

DSPE-PEG-Mal

DSPE-PEG-NH2

DSPE-PEG-NHS

DSPE-PEG-OH

DSPE-PEG-propargyl

DSPE-PEG-Alkyne

DSPE-PEG-Rhodamine

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