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Effect of PEG Pairing on the Efficiency of Cancer-Targeting Liposomes

Standardized poly(ethylene glycol)-modified (PEGylated) liposomes, which have been widely used in research as well as in pre-clinical and clinical studies, are typically constructed using PEG with a molecular weight of 2000 Da (PEG(2000)). Targeting ligands are also generally conjugated using variou...

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Autores principales: Saw, Phei Er, Park, Jinho, Lee, Eunbeol, Ahn, Sukyung, Lee, Jinju, Kim, Hyungjun, Kim, Jinjoo, Choi, Minsuk, Farokhzad, Omid C., Jon, Sangyong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4402498/
https://www.ncbi.nlm.nih.gov/pubmed/25897339
http://dx.doi.org/10.7150/thno.10732
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author Saw, Phei Er
Park, Jinho
Lee, Eunbeol
Ahn, Sukyung
Lee, Jinju
Kim, Hyungjun
Kim, Jinjoo
Choi, Minsuk
Farokhzad, Omid C.
Jon, Sangyong
author_facet Saw, Phei Er
Park, Jinho
Lee, Eunbeol
Ahn, Sukyung
Lee, Jinju
Kim, Hyungjun
Kim, Jinjoo
Choi, Minsuk
Farokhzad, Omid C.
Jon, Sangyong
author_sort Saw, Phei Er
collection PubMed
description Standardized poly(ethylene glycol)-modified (PEGylated) liposomes, which have been widely used in research as well as in pre-clinical and clinical studies, are typically constructed using PEG with a molecular weight of 2000 Da (PEG(2000)). Targeting ligands are also generally conjugated using various functionalized PEG(2000). However, although standardized protocols have routinely used PEG(2000), it is not because this molecular weight PEG has been optimized to enhance tumor uptake of nanoparticles. Herein, we investigated the effect of various PEG lipid pairings—that is, PEG lipids for targeting-ligand conjugation and PEG lipids for achieving 'stealth' function—on in vitro cancer cell- and in vivo tumor-targeting efficacy. A class of high-affinity peptides (aptides) specific to extra domain B of fibronectin (APT(EDB)) was used as a representative model for a cancer-targeting ligand. We synthesized a set of aptide-conjugated PEGylated phospholipids (APT(EDB)‑PEG(2000)‑DSPE and APT(EDB)‑PEG(1000)‑DSPE) and then paired them with methoxy-capped PEGylated phospholipids with diverse molecular weights (PEG(2000), PEG(1000), PEG(550), and PEG(350)) to construct various aptide-conjugated PEGylated liposomes. The liposomes with APT(EDB)‑PEG(2000)/PEG(1000) and APT(EDB)‑PEG(1000)/PEG(550) pairings had the highest uptake in EDB-positive cancer cells. Furthermore, in a U87MG xenograft model, APT(EDB)‑PEG(2000)/PEG(1000) liposomes retarded tumor growth to the greatest extent, followed closely by APT(EDB)‑PEG(1000)/PEG(550) liposomes. Among the PEGylated liposomes tested, pairs in which the methoxy-capped PEG length was about half that of the targeting ligand-displaying PEG exhibited the best performance, suggesting that PEG pairing is a key consideration in the design of drug-delivery vehicles.
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spelling pubmed-44024982015-04-20 Effect of PEG Pairing on the Efficiency of Cancer-Targeting Liposomes Saw, Phei Er Park, Jinho Lee, Eunbeol Ahn, Sukyung Lee, Jinju Kim, Hyungjun Kim, Jinjoo Choi, Minsuk Farokhzad, Omid C. Jon, Sangyong Theranostics Research Paper Standardized poly(ethylene glycol)-modified (PEGylated) liposomes, which have been widely used in research as well as in pre-clinical and clinical studies, are typically constructed using PEG with a molecular weight of 2000 Da (PEG(2000)). Targeting ligands are also generally conjugated using various functionalized PEG(2000). However, although standardized protocols have routinely used PEG(2000), it is not because this molecular weight PEG has been optimized to enhance tumor uptake of nanoparticles. Herein, we investigated the effect of various PEG lipid pairings—that is, PEG lipids for targeting-ligand conjugation and PEG lipids for achieving 'stealth' function—on in vitro cancer cell- and in vivo tumor-targeting efficacy. A class of high-affinity peptides (aptides) specific to extra domain B of fibronectin (APT(EDB)) was used as a representative model for a cancer-targeting ligand. We synthesized a set of aptide-conjugated PEGylated phospholipids (APT(EDB)‑PEG(2000)‑DSPE and APT(EDB)‑PEG(1000)‑DSPE) and then paired them with methoxy-capped PEGylated phospholipids with diverse molecular weights (PEG(2000), PEG(1000), PEG(550), and PEG(350)) to construct various aptide-conjugated PEGylated liposomes. The liposomes with APT(EDB)‑PEG(2000)/PEG(1000) and APT(EDB)‑PEG(1000)/PEG(550) pairings had the highest uptake in EDB-positive cancer cells. Furthermore, in a U87MG xenograft model, APT(EDB)‑PEG(2000)/PEG(1000) liposomes retarded tumor growth to the greatest extent, followed closely by APT(EDB)‑PEG(1000)/PEG(550) liposomes. Among the PEGylated liposomes tested, pairs in which the methoxy-capped PEG length was about half that of the targeting ligand-displaying PEG exhibited the best performance, suggesting that PEG pairing is a key consideration in the design of drug-delivery vehicles. Ivyspring International Publisher 2015-04-05 /pmc/articles/PMC4402498/ /pubmed/25897339 http://dx.doi.org/10.7150/thno.10732 Text en © 2015 Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions.
spellingShingle Research Paper
Saw, Phei Er
Park, Jinho
Lee, Eunbeol
Ahn, Sukyung
Lee, Jinju
Kim, Hyungjun
Kim, Jinjoo
Choi, Minsuk
Farokhzad, Omid C.
Jon, Sangyong
Effect of PEG Pairing on the Efficiency of Cancer-Targeting Liposomes
title Effect of PEG Pairing on the Efficiency of Cancer-Targeting Liposomes
title_full Effect of PEG Pairing on the Efficiency of Cancer-Targeting Liposomes
title_fullStr Effect of PEG Pairing on the Efficiency of Cancer-Targeting Liposomes
title_full_unstemmed Effect of PEG Pairing on the Efficiency of Cancer-Targeting Liposomes
title_short Effect of PEG Pairing on the Efficiency of Cancer-Targeting Liposomes
title_sort effect of peg pairing on the efficiency of cancer-targeting liposomes
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4402498/
https://www.ncbi.nlm.nih.gov/pubmed/25897339
http://dx.doi.org/10.7150/thno.10732
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