Effect of PEG Pairing on the Efficiency of Cancer-Targeting Liposomes
| Autor: | Phei Er Saw, Eunbeol Lee, Jinho Park, Jinjoo Kim, Minsuk Choi, Jinju Lee, Omid C. Farokhzad, Hyungjun Kim, Sukyung Ahn, Sangyong Jon |
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| Rok vydání: | 2015 |
| Předmět: |
Mice
Nude Medicine (miscellaneous) aptides · liposomes · cancer therapy · poly(ethylene glycol) · drug delivery · extra domain B of fibronectin Antineoplastic Agents macromolecular substances Conjugated system Polyethylene Glycols Mice chemistry.chemical_compound In vivo Cell Line Tumor PEG ratio Animals Humans Pharmacology Toxicology and Pharmaceutics (miscellaneous) Phospholipids Mice Inbred BALB C Liposome Molecular mass Chemistry technology industry and agriculture Ligand (biochemistry) In vitro aptides liposomes cancer therapy poly(ethylene glycol) drugdelivery extra domain B of fibronectin Biochemistry Liposomes Female Peptides Ethylene glycol Research Paper |
| Zdroj: | THERANOSTICS(5): 7 Theranostics |
| ISSN: | 1838-7640 |
| DOI: | 10.7150/thno.10732 |
| Popis: | 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(2000))‑DSPE) and then paired them with methoxy-capped PEGylated phospholipids with diverse molecular weights (PEG(2000)), PEG(2000)), PEG(2000)), and PEG(2000))) to construct various aptide-conjugated PEGylated liposomes. The liposomes with APT(EDB)‑PEG(2000))/PEG(2000)) and APT(EDB)‑PEG(2000))/PEG(2000)) pairings had the highest uptake in EDB-positive cancer cells. Furthermore, in a U87MG xenograft model, APT(EDB)‑PEG(2000))/PEG(2000)) liposomes retarded tumor growth to the greatest extent, followed closely by APT(EDB)‑PEG(2000))/PEG(2000)) 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. |
| Databáze: | OpenAIRE |
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