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A brain tumor-homing tetra-peptide delivers a nano-therapeutic for more effective treatment of a mouse model of glioblastoma.
- Source :
-
Nanoscale horizons [Nanoscale Horiz] 2020 Jul 27; Vol. 5 (8), pp. 1213-1225. - Publication Year :
- 2020
-
Abstract
- 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.
- Subjects :
- Animals
Annexin A3 chemistry
Cell Line, Tumor
Female
Humans
Mice, Inbred BALB C
Mice, Nude
Nanoparticles chemistry
Peptide Fragments chemistry
Polyethylene Glycols chemistry
Silicon chemistry
Xenograft Model Antitumor Assays
Antineoplastic Agents therapeutic use
Cell-Penetrating Peptides chemistry
Drug Carriers chemistry
Glioblastoma drug therapy
Irinotecan therapeutic use
Oligopeptides chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 2055-6764
- Volume :
- 5
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Nanoscale horizons
- Publication Type :
- Academic Journal
- Accession number :
- 32510090
- Full Text :
- https://doi.org/10.1039/d0nh00077a