A brain tumor-homing tetra-peptide delivers a nano-therapeutic for more effective treatment of a mouse model of glioblastoma
| Autor: | Eugene Huh, Dokyoung Kim, Seung Geun Yeo, Jeong Eun Jang, Seong Jae Kang, Rae Hyung Kang, Hyo Young Kim, Michael J. Sailor, Dae-Ro Ahn, Myung Sook Oh, Jae Seung Kang |
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| Rok vydání: | 2020 |
| Předmět: |
Silicon
Brain tumor Mice Nude Peptide Antineoplastic Agents 02 engineering and technology Cell-Penetrating Peptides Irinotecan Polyethylene Glycols 03 medical and health sciences In vivo Cell Line Tumor PEG ratio medicine Animals Humans General Materials Science Peptide sequence Annexin A3 030304 developmental biology chemistry.chemical_classification 0303 health sciences Gene knockdown Drug Carriers Mice Inbred BALB C 021001 nanoscience & nanotechnology medicine.disease Xenograft Model Antitumor Assays In vitro Peptide Fragments chemistry Cancer research Nanoparticles Female 0210 nano-technology Glioblastoma Linker Oligopeptides |
| Zdroj: | Nanoscale horizons. 5(8) |
| ISSN: | 2055-6764 |
| Popis: | Organ-specific cell-penetrating peptides (CPPs) are a class of molecules that can be highly effective at delivering therapeutic cargoes, and they are currently of great interest in cancer treatment strategies. Herein, we describe a new CPP (amino acid sequence serine-isoleucine-tyrosine-valine, or SIWV) that homes to glioblastoma multiforme (GBM) brain tumor tissues with remarkable specificity in vitro and in vivo. The SIWV sequence was identified from an isoform of annexin-A3 (AA3H), a membrane-interacting human protein. The mechanism of intracellular permeation is proposed to follow a caveolin-mediated endocytotic pathway, based on in vitro and in vivo receptor inhibition and genetic knockdown studies. Feasibility as a targeting agent for therapeutics is demonstrated in a GBM xenograft mouse model, where porous silicon nanoparticles (pSiNPs) containing the clinically relevant anticancer drug SN-38 are grafted with SIWV via a poly-(ethylene glycol) (PEG) linker. The formulation shows enhanced in vivo targeting ability relative to a formulation employing a scrambled control peptide, and significant (P < 0.05) therapeutic efficacy relative to free SN-38 in the GBM xenograft animal model. |
| Databáze: | OpenAIRE |
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