Tumor‐Targeting Multifunctional Nanoparticles for siRNA Delivery: Recent Advances in Cancer Therapy

Ku, Sook Hee; Kim, Kwang Meyung; Choi, Kuiwon; Kim, Sun Hwa; Kwon, Ick Chan

doi:10.1002/adhm.201300607

Cited by 69 publications

(58 citation statements)

References 103 publications

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“…However, these vessels are not always the best option, because they may be occluded or diseased, especially transport genes without exhibiting any toxicity and immune responses, and can be synthesized in a large scale. [ 20,21 ] Recently, the use of nonviral carriers such as polycationic polymers, polymeric micelles, and nanoparticles to deliver plasmid DNA (pDNA) has been highlighted. [22][23][24] Polycationic polymers have the ability to physically bind pDNA, and can be applied to a variety of cells.…”

Section: Introductionmentioning

confidence: 99%

Nanoparticles Complexed with Gene Vectors to Promote Proliferation of Human Vascular Endothelial Cells

Shi

Zhang

et al. 2015

Adv Healthcare Materials

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Amphiphilic block copolymers containing biodegradable hydrophobic segments of depsipeptide based copolymers have been synthesized and explored as gene carriers for enhancing proliferation of endothelial cells in vitro. These polymers form nanoparticles (NPs) with positive charges on their surface, which could condense recombinant plasmids of enhanced green fluorescent protein plasmid and ZNF580 gene (pEGFP-ZNF580) and protect them against DNase I. ZNF580 gene is efficiently transported into EA.hy926 cells to promote their proliferation, whereby the transfection efficiency of NPs/pEGFP-ZNF580 is approximately similar to that of Lipofectamine 2000. These results indicate that the NPs might have potential as a carrier for pEGFP-ZNF580, which could support endothelialization of cardiovascular implants.

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Section: Introductionmentioning

confidence: 99%

Nanoparticles Complexed with Gene Vectors to Promote Proliferation of Human Vascular Endothelial Cells

Shi

Zhang

et al. 2015

Adv Healthcare Materials

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“…A variety of nanocarriers including MSNPs have been utilized to deliver siRNA in vitro and in vivo [159, 218, 273, 274]. The earliest studies utilized the MSNP surface and a protective polymer coating to encapsulate and protect siRNA [268, 275–277].…”

Section: Nanocarriersmentioning

confidence: 99%

Ligand-targeted theranostic nanomedicines against cancer

Yao¹,

D’Angelo²,

Butler

et al. 2016

Journal of Controlled Release

164

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Nanomedicines have significant potential for cancer treatment. Although the majority of nanomedicines currently tested in clinical trials utilize simple, biocompatible liposome-based nanocarriers, their widespread use is limited by non-specificity and low target site concentration and thus, do not provide a substantial clinical advantage over conventional, systemic chemotherapy. In the past 20 years, we have identified specific receptors expressed on the surfaces of tumor endothelial and perivascular cells, tumor cells, the extracellular matrix and stromal cells using combinatorial peptide libraries displayed on bacteriophage. These studies corroborate the notion that unique receptor proteins such as IL-11Rα, GRP78, EphA5, among others, are differentially overexpressed in tumors and present opportunities to deliver tumor-specific therapeutic drugs. By using peptides that bind to tumor-specific cell-surface receptors, therapeutic agents such as apoptotic peptides, suicide genes, imaging dyes or chemotherapeutics can be precisely and systemically delivered to reduce tumor growth in vivo, without harming healthy cells. Given the clinical applicability of peptide-based therapeutics, targeted delivery of nanocarriers loaded with therapeutic cargos seems plausible. We propose a modular design of a functionalized protocell in which a tumor-targeting moiety, such as a peptide or recombinant human antibody single chain variable fragment (scFv), is conjugated to a lipid bilayer surrounding a silica-based nanocarrier core containing a protected therapeutic cargo. The functionalized protocell can be tailored to a specific cancer subtype and treatment regimen by exchanging the tumor-targeting moiety and/or therapeutic cargo or used in combination to create unique, theranostic agents. In this review, we summarize the identification of tumor-specific receptors through combinatorial phage display technology and the use of antibody display selection to identify recombinant human scFvs against these tumor-specific receptors. We compare the characteristics of different types of simple and complex nanocarriers, and discuss potential types of therapeutic cargos and conjugation strategies. The modular design of functionalized protocells may improve the efficacy and safety of nanomedicines for future cancer therapy.

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“…Recently, investigators have begun to design multifunctional or modular delivery agents [14], whereby the different materials/components address one or more facets of efficient delivery and the combination fulfills all or most of the properties of an efficient delivery agent.…”

Section: Introductionmentioning

confidence: 99%

Delivery of gene targeting siRNAs to breast cancer cells using a multifunctional peptide complex that promotes both targeted delivery and endosomal release

2017

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RNA interference has been used to dissect the importance of individual gene products in various human disease processes, including cancer. Small-interfering RNA, or siRNA, is one of the tools utilized in this regard, but specially-designed delivery agents are required to allow the siRNA to gain optimal access to the cell interior. Our laboratory has utilized two different siRNA-binding delivery peptides containing a polyarginine core, and modified by myristoylation and targeting motifs (iRGD or Lyp-1). A third peptide was designed to assist with endosomal release. Various ratios of the peptides and siRNA were combined and assayed for the ability to form stable complexes, and optimized ratios were determined. The complexes were found to form particles, with the majority having a diameter of 100–300 nm, as visualized by electron microscopy. These siRNA complexes have enhanced protection from nucleases present in serum, as compared to “naked” unprotected siRNA. The particles were internalized by the cells and could be detected in the cell cytoplasm by confocal fluorescence microscopy. In functional assays, peptide/siRNA complexes were shown to cause the knock down of corresponding targeted proteins. The peptide with the LyP-1 targeting motif was more effective at knockdown in MDA-MB-231 breast cancer cells than the peptide with the iRGD motif. Inclusion of the endosomal release peptide in the complexes greatly enhanced the peptide/siRNA effects. Peptide/siRNA complexes simultaneously targeting Stat3 and c-Myc caused a marked reduction in anchorage-independent growth, a property correlated with tumorigenicity. This study demonstrates the ability of a peptide-based siRNA-delivery system to deliver siRNA into breast cancer cells and cause both protein knockdown and suppression of the malignant phenotype. Such peptide complexes are likely to become highly useful siRNA-delivery vehicles for the characterization, and potentially for the treatment, of human cancer.

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Tumor‐Targeting Multifunctional Nanoparticles for siRNA Delivery: Recent Advances in Cancer Therapy

Cited by 69 publications

References 103 publications

Nanoparticles Complexed with Gene Vectors to Promote Proliferation of Human Vascular Endothelial Cells

Nanoparticles Complexed with Gene Vectors to Promote Proliferation of Human Vascular Endothelial Cells

Ligand-targeted theranostic nanomedicines against cancer

Delivery of gene targeting siRNAs to breast cancer cells using a multifunctional peptide complex that promotes both targeted delivery and endosomal release

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