Local Targeted Therapy of Liver Metastasis from Colon Cancer by Galactosylated Liposome Encapsulated with Doxorubicin

Abstract

Since regional drug administration enables to maintain a high drug concentration within tumors, we compared the plasma concentration and biodistribution of doxorubicin (Dox) from drug-loaded conventional liposomes by local or systemic administration. The results demonstrated that drug concentration was substantially improved in liver as well as a decrease in blood and other organs by spleen injection mimicking portal vein perfusion (regional administration). To further investigate the targeted therapeutic effect of galactosylated liposome encapsulated doxorubicin (Dox) by regional administration, liver targeting liposomes were prepared by incorporating galactosylated-DPPE to conventional liposomes. Liposome uptake and targeting were verified in vitro and in vivo by fluorescence microscopy and xenogen IVIS imaging system, respectively. The results showed that galactose targeted liposomes presented a stronger specific cell uptake by human hepatocellular carcinoma HepG2 cells compared to the non-targeted liposomes. In vivo fluorescence imaging showed that the intra-hepatic deposition of conventional and galactosylated liposomes via spleen injection was more than that via tail vein administration, and galactosylated liposomes had higher fluorescent intensity over conventional liposomes in the liver post spleen administration. The anti-tumor effect of various drug administration routes for both liposomal formulations was evaluated using a murine liver metastasis model of colon cancer. The results indicated that tumor progression in the liver and mesenteric lymph nodes was significantly suppressed by Dox-loaded galactosylated liposomes via spleen injection, while no significance was observed in non-targeted formulations. Our data indicated that local perfusion of galactosylated liposomal doxorubicin had a great promise for the treatment of liver metastasis from colon cancer.

Inhibition of colon cancer cell growth by nanoemulsion carrying gold nanoparticles and lycopene

“…11 For improvements in cancer therapy efficiency, and reductions of host toxicity in vivo, nanoparticles have been modified by the incorporation of liposomes, polymeric materials, and dendrimers, with lipid-based nanoassemblies being the least toxic. 12,13 In view of this, it is possible to enhance cancer therapy through the conjugation of AN with lipid-based nanoemulsion containing lycopene (LP). Additionally, one of the major advantages of AN is that they can be manufactured into sizes that range from 1-150 nm, 8 but the effect of various sized AN on colon cancer cell growth remains uncertain.…”

“…13 This study aims to explore the inhibition mechanism of the colon cancer cell line, HT-29, as affected by various treatments including AN or LP alone, a combination of AN plus LP, as well as the nanoemulsion of AN plus LP. Also, the possible cell uptake mechanism and passive targeting effect of the nanoemulsion developed in this experiment will be elucidated.…”

Hepatic Tumor Metastases Cause Enhanced PEGylated Liposome Uptake by Kupffer Cells

“…10) In metastatic hepatic cancer, Zhao et al reported that a local perfusion of doxorubicin-loaded galactosylated liposomes is effective for liver metastasis from colorectal cancer. 11) Kupffer cells were thought to be responsible for the hepatic accumulation of liposomes. 12,13) Kupffer cells phagocytose invasive pathogens and colloidal nanoparticles such as liposomes.…”

The effect of macrophage phenotype and surface modification of liposomes on internalization

“…2 Currently, liposomes are one of the most widely investigated drug delivery systems and are used in the clinic. 30,31 Seventeen liposomal drug formulations have been clinically approved and many more are in clinical trials. 32,33 Solutes carried by liposomes been extended to chelating agents 34 , antibiotics 35 , hormones 36 , proteins 37 , and anti-tumor drugs.…”

“…A transmembrane pH gradient was employed as an active loading method to encapsulate doxorubicin in liposomes. 31 Through drug self-association and interaction with salts, doxorubicin precipitates…”