title: Effect of PEG pairing on the efficiency of cancer-targeting liposomes.
abstract: 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.
authors.affiliation: 1. KAIST Institute for the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and technology (KAIST), 291 Daehak-ro, Daejeon 305-701, Republic of Korea. ; 2. Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital Harvard Medical School, Boston, MA 02115, U.S.A.
authors.forename: Phei Er
authors.initials: PE
authors.lastname: Saw
authors.affiliation: 1. KAIST Institute for the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and technology (KAIST), 291 Daehak-ro, Daejeon 305-701, Republic of Korea.
authors.forename: Jinho
authors.initials: J
authors.lastname: Park
authors.affiliation: 1. KAIST Institute for the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and technology (KAIST), 291 Daehak-ro, Daejeon 305-701, Republic of Korea.
authors.forename: Eunbeol
authors.initials: E
authors.lastname: Lee
authors.affiliation: 1. KAIST Institute for the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and technology (KAIST), 291 Daehak-ro, Daejeon 305-701, Republic of Korea.
authors.forename: Sukyung
authors.initials: S
authors.lastname: Ahn
authors.affiliation: 3. School of Life Sciences, Gwangju Institute of Science and Technology, 123-Cheomdangwagi-ro, Gwangju 500-712, Republic of Korea.
authors.forename: Jinju
authors.initials: J
authors.lastname: Lee
authors.affiliation: 1. KAIST Institute for the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and technology (KAIST), 291 Daehak-ro, Daejeon 305-701, Republic of Korea.
authors.forename: Hyungjun
authors.initials: H
authors.lastname: Kim
authors.affiliation: 1. KAIST Institute for the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and technology (KAIST), 291 Daehak-ro, Daejeon 305-701, Republic of Korea.
authors.forename: Jinjoo
authors.initials: J
authors.lastname: Kim
authors.affiliation: 1. KAIST Institute for the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and technology (KAIST), 291 Daehak-ro, Daejeon 305-701, Republic of Korea.
authors.forename: Minsuk
authors.initials: M
authors.lastname: Choi
authors.affiliation: 2. Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital Harvard Medical School, Boston, MA 02115, U.S.A.
authors.forename: Omid C
authors.initials: OC
authors.lastname: Farokhzad
authors.affiliation: 1. KAIST Institute for the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and technology (KAIST), 291 Daehak-ro, Daejeon 305-701, Republic of Korea.
authors.forename: Sangyong
authors.initials: S
authors.lastname: Jon
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008081:Liposomes / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010455:Peptides / Q000008:administration & dosage*; D010743:Phospholipids / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: C000601127:APT(EDB) peptide; D000970:Antineoplastic Agents; D008081:Liposomes; D010455:Peptides; D010743:Phospholipids; D011092:Polyethylene Glycols
keywords: aptides · liposomes · cancer therapy · poly(ethylene glycol) · drug delivery · extra domain B of fibronectin