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Effects of PEG-Linker Chain Length of Folate-Linked Liposomal Formulations on Targeting Ability and Antitumor Activity of Encapsulated Drug

INTRODUCTION: Ligand-conjugated liposomes are promising for the treatment of specific receptor-overexpressing cancers. However, previous studies have shown inconsistent results because of the varying properties of the ligand, presence of a polyethylene glycol (PEG) coating on the liposome, length of...

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Autores principales: Lim, Chaemin, Shin, Yuseon, Kang, Kioh, Husni, Patihul, Lee, Dayoon, Lee, Sehwa, Choi, Han-Gon, Lee, Eun Seong, Youn, Yu Seok, Oh, Kyung Taek
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10069508/
https://www.ncbi.nlm.nih.gov/pubmed/37020691
http://dx.doi.org/10.2147/IJN.S402418
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author Lim, Chaemin
Shin, Yuseon
Kang, Kioh
Husni, Patihul
Lee, Dayoon
Lee, Sehwa
Choi, Han-Gon
Lee, Eun Seong
Youn, Yu Seok
Oh, Kyung Taek
author_facet Lim, Chaemin
Shin, Yuseon
Kang, Kioh
Husni, Patihul
Lee, Dayoon
Lee, Sehwa
Choi, Han-Gon
Lee, Eun Seong
Youn, Yu Seok
Oh, Kyung Taek
author_sort Lim, Chaemin
collection PubMed
description INTRODUCTION: Ligand-conjugated liposomes are promising for the treatment of specific receptor-overexpressing cancers. However, previous studies have shown inconsistent results because of the varying properties of the ligand, presence of a polyethylene glycol (PEG) coating on the liposome, length of the linker, and density of the ligand. METHODS: Here, we prepared PEGylated liposomes using PEG-linkers of various lengths conjugated with folate and evaluated the effect of the PEG-linker length on the nanoparticle distribution and pharmacological efficacy of the encapsulated drug both in vitro and in vivo. RESULTS: When folate was conjugated to the liposome surface, the cellular uptake efficiency in folate receptor overexpressed KB cells dramatically increased compared to that of the normal liposome. However, when comparing the effect of the PEG-linker length in vitro, no significant difference between the formulations was observed. In contrast, the level of tumor accumulation of particles in vivo significantly increased when the length of the PEG-linker was increased. The tumor size was reduced by >40% in the Dox/FL-10K-treated group compared to that in the Dox/FL-2K- or 5K-treated groups. DISCUSSION: Our study suggests that as the length of PEG-linker increases, the tumor-targeting ability can be enhanced under in vivo conditions, which can lead to an increase in the antitumor activity of the encapsulated drug.
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spelling pubmed-100695082023-04-04 Effects of PEG-Linker Chain Length of Folate-Linked Liposomal Formulations on Targeting Ability and Antitumor Activity of Encapsulated Drug Lim, Chaemin Shin, Yuseon Kang, Kioh Husni, Patihul Lee, Dayoon Lee, Sehwa Choi, Han-Gon Lee, Eun Seong Youn, Yu Seok Oh, Kyung Taek Int J Nanomedicine Original Research INTRODUCTION: Ligand-conjugated liposomes are promising for the treatment of specific receptor-overexpressing cancers. However, previous studies have shown inconsistent results because of the varying properties of the ligand, presence of a polyethylene glycol (PEG) coating on the liposome, length of the linker, and density of the ligand. METHODS: Here, we prepared PEGylated liposomes using PEG-linkers of various lengths conjugated with folate and evaluated the effect of the PEG-linker length on the nanoparticle distribution and pharmacological efficacy of the encapsulated drug both in vitro and in vivo. RESULTS: When folate was conjugated to the liposome surface, the cellular uptake efficiency in folate receptor overexpressed KB cells dramatically increased compared to that of the normal liposome. However, when comparing the effect of the PEG-linker length in vitro, no significant difference between the formulations was observed. In contrast, the level of tumor accumulation of particles in vivo significantly increased when the length of the PEG-linker was increased. The tumor size was reduced by >40% in the Dox/FL-10K-treated group compared to that in the Dox/FL-2K- or 5K-treated groups. DISCUSSION: Our study suggests that as the length of PEG-linker increases, the tumor-targeting ability can be enhanced under in vivo conditions, which can lead to an increase in the antitumor activity of the encapsulated drug. Dove 2023-03-30 /pmc/articles/PMC10069508/ /pubmed/37020691 http://dx.doi.org/10.2147/IJN.S402418 Text en © 2023 Lim et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Lim, Chaemin
Shin, Yuseon
Kang, Kioh
Husni, Patihul
Lee, Dayoon
Lee, Sehwa
Choi, Han-Gon
Lee, Eun Seong
Youn, Yu Seok
Oh, Kyung Taek
Effects of PEG-Linker Chain Length of Folate-Linked Liposomal Formulations on Targeting Ability and Antitumor Activity of Encapsulated Drug
title Effects of PEG-Linker Chain Length of Folate-Linked Liposomal Formulations on Targeting Ability and Antitumor Activity of Encapsulated Drug
title_full Effects of PEG-Linker Chain Length of Folate-Linked Liposomal Formulations on Targeting Ability and Antitumor Activity of Encapsulated Drug
title_fullStr Effects of PEG-Linker Chain Length of Folate-Linked Liposomal Formulations on Targeting Ability and Antitumor Activity of Encapsulated Drug
title_full_unstemmed Effects of PEG-Linker Chain Length of Folate-Linked Liposomal Formulations on Targeting Ability and Antitumor Activity of Encapsulated Drug
title_short Effects of PEG-Linker Chain Length of Folate-Linked Liposomal Formulations on Targeting Ability and Antitumor Activity of Encapsulated Drug
title_sort effects of peg-linker chain length of folate-linked liposomal formulations on targeting ability and antitumor activity of encapsulated drug
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10069508/
https://www.ncbi.nlm.nih.gov/pubmed/37020691
http://dx.doi.org/10.2147/IJN.S402418
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