title: Glioma-homing peptide with a cell-penetrating effect for targeting delivery with enhanced glioma localization, penetration and suppression of glioma growth.
abstract: Tumor-targeted delivery systems are useful in enhancing drug delivery and increasing anti-tumor effects. Cell-penetrating peptides have been widely used for this purpose but have been hampered by the poor selectivity between neoplastic and non-neoplastic cells. As a peptide derived from interleukin-13, interleukin-13 peptide (IL-13p) is specifically targeted to IL13Rα2, a tumor-restricted receptor. More interestingly, IL-13p possesses cell-penetrating properties that can specifically enhance the uptake by tumor cells compared with endothelial cells. Thus, we anchored IL-13p onto nanoparticles (ILNPs) for glioma-targeting delivery. The uptake of ILNPs by U87 cells was higher than that of unmodified nanoparticles (NPs). However, there was no significant difference in the uptake by human umbilical vein endothelial cells. In addition, free IL-13p could also enhance the uptake of both NPs and ILNPs by U87 cells. Anchoring with IL-13p could enhance the penetration of particles into the core of spheroids. In vivo, the fluorescence intensity of ILNPs in tumors was 2.96-fold higher than that of NPs. The modification with IL-13p also significantly improved the speed and rate of penetration from vessels to tumor cells. The enhanced tumor localization of ILNPs was mostly attributable to the elevated tumor cell internalization of ILNPs, whereas most NPs were colocalized with microvessels or macrophages. Correspondingly, docetaxel-loaded NPs effectively suppressed the growth of subcutaneous U87 tumors. The average tumor volume of the ILNP group was only 31.4% that of the control, which was significantly smaller than that of the docetaxel and NP groups. In conclusion, the modification of IL-13p selectively enhanced tumor cell uptake, improved the penetration effect of NPs and improved the glioma localization ability, which led to a better tumor-suppression effect.
authors.affiliation: School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Huile
authors.initials: H
authors.lastname: Gao
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yang
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhang
authors.forename: Shijie
authors.initials: S
authors.lastname: Cao
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Pang
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.forename: Xinguo
authors.initials: X
authors.lastname: Jiang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000737:chemistry* / Q000378:metabolism; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018793:Interleukin-13 / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D053758:Nanoparticles / Q000737:chemistry; D043823:Taxoids / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D018793:Interleukin-13; D043823:Taxoids; D000077143:Docetaxel
keywords: Glioma-homing peptide; Penetration; Targeted delivery systems