title: Facilitated intracellular delivery of peptide-guided nanoparticles in tumor tissues.
abstract: Macromolecular nanoparticles can extravasate and accumulate within tumor tissues via the passive targeting system, reflecting enhanced permeability and the retention effect. However, the unsatisfactory tumor therapeutic efficacy of the passive-targeting system, attributable to the retention of extravasated nanoparticles in the vicinity of tumor vessels, argues that a new system that facilitates intracellular delivery of nanoparticles within tumors is needed. Here, we developed hydrophobically modified glycol chitosan (HGC) nanoparticles conjugated with interleukin-4 receptor (IL-4R) binding peptides, termed I4R, and tested them in mice bearing IL-4R-positive tumors. These HGC-I4R nanoparticles exhibited enhanced IL-4R-dependent cellular uptake in tumors compared to nonconjugated nanoparticles, leading to better therapeutic and imaging efficacy. We conclude that I4R facilitates and enhances cellular uptake of nanoparticles in tumor tissues. This study suggests that the intracelluar uptake of nanoparticles in tumors is an essential factor to consider in designing nanoparticles for tumor-targeted drug delivery and imaging.
authors.affiliation: Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, 101 Dongin 2Ga, Jung-Gu, Daegu 700-422, South Korea.
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Kim
authors.forename: Sang Mun
authors.initials: SM
authors.lastname: Bae
authors.forename: Moon-Hee
authors.initials: MH
authors.lastname: Na
authors.forename: Hyeri
authors.initials: H
authors.lastname: Shin
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Yang
authors.forename: Kyung Hyun
authors.initials: KH
authors.lastname: Min
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Choi
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
authors.forename: Rang-Woon
authors.initials: RW
authors.lastname: Park
authors.forename: Ick Chan
authors.initials: IC
authors.lastname: Kwon
authors.forename: Byung-Heon
authors.initials: BH
authors.lastname: Lee
authors.forename: Allan S
authors.initials: AS
authors.lastname: Hoffman
authors.forename: In-San
authors.initials: IS
authors.lastname: Kim
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009842:Oligopeptides / Q000008:administration & dosage* / Q000737:chemistry; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry; D019948:Receptors, Interleukin-4 / Q000008:administration & dosage* / Q000737:chemistry; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D009842:Oligopeptides; D019948:Receptors, Interleukin-4; C118638:glycol-chitosan; D048271:Chitosan; D017239:Paclitaxel