Using Doxorubicin-loaded poly(L-glutamic acid)-b-polyglycine-g-lactobionolactone micelles as potential therapeutic agents for Hepatocellular carcinoma
Date Issued
2014
Date
2014
Author(s)
How, Su-Chun
Abstract
Amphiphilic polypeptide-based copolymers self-assemble to form micelles.Because the micelles can encapsulate large quantities of cargoes, and have good stability and biocompatibility, they have been widely studied for use as bioactive agents or drugs in recent years.
We used saccharide-modified copolypeptides, poly (L-glutamic acid)-bpolyglycine-g-lactobionolactone (LGG), which self-assembled to form micelles as our carrier for encapsulating an anticancer drug doxorubicin (DOX). We employed the pH gradient between inside and outside of the micelles and sonication to diffuse DOX to the interior of the micelles, and to achieve a high level of the drug encapsulation efficiency(%) of about 40wt%. Cell culture experiments were conducted by using HepG2 liver cancer cells as our model. Toxicity of micelles formed from self-assembling of saccharide-modified copolypeptide, poly(L-Glutamic acid)-b-polyglycine-g-lacto-bionolactone (LGG) was studied. It was discovered that LGG is non-toxic to the cells even in a high-dose DOX condition. When DOX-loaded LGG micelles were compared with DOX-loaded poly(L-glutamic acid)-b-polyglycine (GG) micelles and free DOX, it was observed that they have comparable cytotoxicities under the same DOX-dose condition. Givem that saccharide is a model targeted ligand to HepG2 liver cancer cells,DOX-loaded LGG micelles have more apparent therapeutic effect than DOX-loaded GG and free-DOX at the same low DOX-dose condition.
In this work, apart from using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay to examine the viability of the cells, flow cytometry was utilized to analyze the apoptosis pathway of cells and the cellular uptake.
Subjects
醣基修飾共多肽
自組裝微胞
細胞凋亡
SDGs
Type
thesis
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