PH-Sensitive SiRNA Nanovector for Targeted Gene Silencing and Cytotoxic Effect in Cancer Cells

Overview

Journal Mol Pharm

Publisher American Chemical Society

Specialty Pharmacology

Date 2010 Aug 21

PMID 20722417

Citations 32

Authors

Hyejung Mok

Omid Veiseh

Chen Fang

Forrest M Kievit

Freddy Y Wang

James O Park

Miqin Zhang

Affiliations

Soon will be listed here.

Abstract

A small interfering RNA (siRNA) nanovector with dual targeting specificity and dual therapeutic effect is developed for targeted cancer imaging and therapy. The nanovector is composed of an iron oxide magnetic nanoparticle core coated with three different functional molecules: polyethyleneimine (PEI), siRNA, and chlorotoxin (CTX). The primary amine group of PEI is blocked with citraconic anhydride that is removable at acidic conditions, not only to increase its biocompatibility at physiological conditions but also to elicit a pH-sensitive cytotoxic effect in the acidic tumor microenvironment. The PEI is covalently immobilized on the nanovector via a disulfide linkage that is cleavable after cellular internalization of the nanovector. CTX as a tumor-specific targeting ligand and siRNA as a therapeutic payload are conjugated on the nanovector via a flexible and hydrophilic PEG linker for targeted gene silencing in cancer cells. With a size of ∼60 nm, the nanovector exhibits long-term stability and good magnetic property for magnetic resonance imaging. The multifunctional nanovector exhibits both significant cytotoxic and gene silencing effects at acidic pH conditions for C6 glioma cells, but not at physiological pH conditions. Our results suggest that this nanovector system could be safely used as a potential therapeutic agent for targeted treatment of glioma as well as other cancers.

Citing Articles

Diagnostic and Therapeutic Approaches for Glioblastoma and Neuroblastoma Cancers Using Chlorotoxin Nanoparticles.

Boltman T, Meyer M, Ekpo O Cancers (Basel). 2023; 15(13).

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Surface Modification of Iron Oxide-Based Magnetic Nanoparticles for Cerebral Theranostics: Application and Prospection.

Wu Y, Lu Z, Li Y, Yang J, Zhang X Nanomaterials (Basel). 2020; 10(8).

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Theranostic Nanoparticles for RNA-Based Cancer Treatment.

Revia R, Stephen Z, Zhang M Acc Chem Res. 2019; 52(6):1496-1506.

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Biodistribution and Toxicity Assessment of Superparamagnetic Iron Oxide Nanoparticles In Vitro and In Vivo.

Yu Q, Xiong X, Zhao L, Xu T, Bi H, Fu R Curr Med Sci. 2018; 38(6):1096-1102.

PMID: 30536075 DOI: 10.1007/s11596-018-1989-8.

Shape-, size- and structure-controlled synthesis and biocompatibility of iron oxide nanoparticles for magnetic theranostics.

Xie W, Guo Z, Gao F, Gao Q, Wang D, Liaw B Theranostics. 2018; 8(12):3284-3307.

PMID: 29930730 PMC: 6010979. DOI: 10.7150/thno.25220.

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