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Temperature-triggered tumor-specific delivery of anticancer agents by cRGD-conjugated thermosensitive liposomes

One of the most effective methods to treat cancer is the specific delivery of anticancer drugs to the target site. To achieve this goal, we designed an anticancer drug with mild hyperthermia-mediated triggering and tumor-specific delivery. To enhance the thermosensitive drug release, we incorporated... Full description

Journal Title: Colloids and Surfaces B: Biointerfaces 01 April 2014, Vol.116, pp.17-25
Main Author: Kim, Min Sang
Other Authors: Lee, Don-Wook , Park, Kitae , Park, Sang-Jun , Choi, Eun-Jung , Park, Eun Sung , Kim, Hyun Ryoung
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 0927-7765 ; E-ISSN: 1873-4367 ; DOI: 10.1016/j.colsurfb.2013.12.045
Link: https://www.sciencedirect.com/science/article/pii/S092777651300800X
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recordid: elsevier_sdoi_10_1016_j_colsurfb_2013_12_045
title: Temperature-triggered tumor-specific delivery of anticancer agents by cRGD-conjugated thermosensitive liposomes
format: Article
creator:
  • Kim, Min Sang
  • Lee, Don-Wook
  • Park, Kitae
  • Park, Sang-Jun
  • Choi, Eun-Jung
  • Park, Eun Sung
  • Kim, Hyun Ryoung
subjects:
  • Drug Delivery
  • Rgd Conjugation
  • Temperature Sensitive
  • Liposome
  • Engineering
  • Chemistry
  • Anatomy & Physiology
ispartof: Colloids and Surfaces B: Biointerfaces, 01 April 2014, Vol.116, pp.17-25
description: One of the most effective methods to treat cancer is the specific delivery of anticancer drugs to the target site. To achieve this goal, we designed an anticancer drug with mild hyperthermia-mediated triggering and tumor-specific delivery. To enhance the thermosensitive drug release, we incorporated elastin-like polypeptide (ELP), which is known to be a thermally responsive phase transition peptide into the dipalmitoylphosphatidylcholine (DPPC)-based liposome surface. Additionally, cyclic arginine-glycine-aspartic acid (cRGD) binds to α β integrin, which is overexpressed in angiogenic vasculature and tumor cells, was introduced on the liposome. ELP-modified liposomes with the cRGD targeting moiety were prepared using a lipid film hydration method, and doxorubicin (DOX) was loaded into the liposome by the ammonium sulfate-gradient method. The cRGD-targeted and ELP-modified DOX-encapsulated liposomes (RELs) formed spherical vesicles with a mean diameter of 181 nm. The RELs showed 75% and 83% DOX release at 42 °C and 45 °C, respectively. The stability of RELs was maintained up to 12 h without the loss of their thermosensitive function for drug release. Flow cytometry results showed that the cellular uptake of DOX in RELs into α β integrin-overexpressing U87MG and HUVEC cells was 8-fold and 10-fold higher, respectively, than that of non-targeting liposomes. Confocal microscopy revealed that REL released DOX only under the mild hyperthermia condition at 42 °C by showing the localization of DOX in nuclei and the liposomes in the cytosol. The cell cytotoxicity results demonstrated that REL can efficiently kill U87MG cells through cRGD targeting and thermal triggering. The in vivo tumoral accumulation measurement showed that the tumor-targeting effect of RELs was 5-fold higher than that of non-targeting liposomes. This stable, target-specific, and thermosensitive liposome shows promise to enhance therapeutic efficacy if it is applied along with a relevant external heat-generating medical system.
language: eng
source:
identifier: ISSN: 0927-7765 ; E-ISSN: 1873-4367 ; DOI: 10.1016/j.colsurfb.2013.12.045
fulltext: fulltext
issn:
  • 0927-7765
  • 09277765
  • 1873-4367
  • 18734367
url: Link


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descriptionOne of the most effective methods to treat cancer is the specific delivery of anticancer drugs to the target site. To achieve this goal, we designed an anticancer drug with mild hyperthermia-mediated triggering and tumor-specific delivery. To enhance the thermosensitive drug release, we incorporated elastin-like polypeptide (ELP), which is known to be a thermally responsive phase transition peptide into the dipalmitoylphosphatidylcholine (DPPC)-based liposome surface. Additionally, cyclic arginine-glycine-aspartic acid (cRGD) binds to α β integrin, which is overexpressed in angiogenic vasculature and tumor cells, was introduced on the liposome. ELP-modified liposomes with the cRGD targeting moiety were prepared using a lipid film hydration method, and doxorubicin (DOX) was loaded into the liposome by the ammonium sulfate-gradient method. The cRGD-targeted and ELP-modified DOX-encapsulated liposomes (RELs) formed spherical vesicles with a mean diameter of 181 nm. The RELs showed 75% and 83% DOX release at 42 °C and 45 °C, respectively. The stability of RELs was maintained up to 12 h without the loss of their thermosensitive function for drug release. Flow cytometry results showed that the cellular uptake of DOX in RELs into α β integrin-overexpressing U87MG and HUVEC cells was 8-fold and 10-fold higher, respectively, than that of non-targeting liposomes. Confocal microscopy revealed that REL released DOX only under the mild hyperthermia condition at 42 °C by showing the localization of DOX in nuclei and the liposomes in the cytosol. The cell cytotoxicity results demonstrated that REL can efficiently kill U87MG cells through cRGD targeting and thermal triggering. The in vivo tumoral accumulation measurement showed that the tumor-targeting effect of RELs was 5-fold higher than that of non-targeting liposomes. This stable, target-specific, and thermosensitive liposome shows promise to enhance therapeutic efficacy if it is applied along with a relevant external heat-generating medical system.
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