Nanoparticle-mediated delivery of suicide genes in cancer therapy

Vago, Riccardo; Collico, Veronica; Zuppone, Stefania; Prosperi, Davide; Colombo, Miriam

doi:10.1016/j.phrs.2016.07.007

Cited by 41 publications

(35 citation statements)

References 184 publications

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“…In particular, nanotechnology has revealed great potential in both increasing efficacy and reducing toxicity of chemotherapy in preclinical and clinical studies of breast cancer [15,16]. Furthermore, nanovectors have been explored for breast cancer gene therapy, including RNA interference (RNAi) approaches, suicide genes delivery, and generation of nano-platforms for the co-delivery of chemotherapeutics and RNA molecules [17][18][19][20]. A schematic overview of non-viral systems, different cargos and functionalization strategies is shown in Figure 1.…”

Section: Non-viral Nanovectorsmentioning

confidence: 99%

“…Major concerns that limited the use of these nanoparticles have been overcome by the coupling with polymeric systems, PEG or lipid shells, reducing aggregation and increasing nanoparticle stealth and cellular penetration [31][32][33]. Different strategies for inorganic nanoparticles functionalization with aptamers or other targeting ligands have greatly improved the selective targeting of breast cancer cells and transfection efficiency [17].…”

Section: Inorganic Nanoparticlesmentioning

confidence: 99%

“…Besides their direct therapeutic application, monoclonal antibodies can be used to confer target selectivity to a wide range of nanoparticles [17]. For instance, trastuzumab functionalization of nanocomplexes enveloping DNA or RNA molecules, including siRNA against B-cell lymphomaextra large (BCL-XL), CXC chemokine receptor 4 (CXCR4), HER2, PLK1, and signal transducer and activator of transcription-3 (STAT3), can be used for the specific targeting of HER2overexpressing breast cancer cells, resulting in an effective therapeutic strategy that combine targeted and gene therapies [27,37,47,80,81].…”

Section: Combinatorial Treatmentsmentioning

confidence: 99%

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Progress in nonviral gene therapy for breast cancer and what comes next?

Bottai

Truffi

Corsi

et al. 2017

Expert Opinion on Biological Therapy

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The possibility of correcting defective genes and modulating gene expression through gene therapy has emerged as a promising treatment strategy for breast cancer. Furthermore, the relevance of tumor immune microenvironment in supporting the oncogenic process has paved the way for novel immunomodulatory applications of gene therapy. Areas covered: In this review, the authors describe the most relevant delivery systems, focusing on nonviral vectors, along with the description of the major approaches used to modify target cells, including gene transfer, RNA interference (RNAi), and epigenetic regulation. Furthermore, they highlight innovative therapeutic strategies and the application of gene therapy in clinical trials for breast cancer. Expert opinion: Gene therapy has the potential to impact breast cancer research. Further efforts are required to increase the clinical application of RNAi-based therapeutics, especially in combination with conventional treatments. Innovative strategies, including genome editing and stem cell-based systems, may contribute to translate gene therapy into clinical practice. Immune-based approaches have emerged as an attractive therapeutic opportunity for selected breast cancer patients. However, several challenges need to be addressed before considering gene therapy as an actual option for the treatment of breast cancer.

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Section: Non-viral Nanovectorsmentioning

confidence: 99%

Section: Inorganic Nanoparticlesmentioning

confidence: 99%

Section: Combinatorial Treatmentsmentioning

confidence: 99%

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Progress in nonviral gene therapy for breast cancer and what comes next?

Bottai

Truffi

Corsi

et al. 2017

Expert Opinion on Biological Therapy

View full text Add to dashboard Cite

show abstract

“…Recent understanding of the barriers to efficient non‐viral vector delivery, such as nanoparticle instability in vivo, poor targeting to specific cells, and inefficient transport through biological barriers such as the cell membrane, has led to an increased number of candidate vectors currently in clinical trials . However, further improvements in these areas are still needed to realise the potential of gene‐based therapies, in particular in the treatment of cancers, where approaches such as suicide gene therapy, regulation of gene expression by delivery of miRNA, p53 replacement gene therapy, and redirection of T‐cell specificity towards cancer cells have recently shown promise. Targeting of nanoparticles to tumors can be passive or active.…”

Section: Introductionmentioning

confidence: 99%

Development of lipopolyplexes for gene delivery: A comparison of the effects of differing modes of targeting peptide display on the structure and transfection activities of lipopolyplexes

Bofinger

Thin

Mitchell

et al. 2018

Journal of Peptide Science

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The design, synthesis and formulation of non‐viral gene delivery vectors is an area of renewed research interest. Amongst the most efficient non‐viral gene delivery systems are lipopolyplexes, in which cationic peptides are co‐formulated with plasmid DNA and lipids. One advantage of lipopolyplex vectors is that they have the potential to be targeted to specific cell types by attaching peptide targeting ligands on the surface, thus increasing both the transfection efficiency and selectivity for disease targets such as cancer cells. In this paper, we have investigated two different modes of displaying cell‐specific peptide targeting ligands at the surface of lipopolyplexes. Lipopolyplexes formulated with bimodal peptides, with both receptor binding and DNA condensing sequences, were compared with lipopolyplexes with the peptide targeting ligand directly conjugated to one of the lipids. Three EGFR targeting peptide sequences were studied, together with a range of lipid formulations and maleimide lipid structures. The biophysical properties of the lipopolyplexes and their transfection efficiencies in a basal‐like breast cancer cell line were investigated using plasmid DNA bearing genes for the expression of firefly luciferase and green fluorescent protein. Fluorescence quenching experiments were also used to probe the macromolecular organisation of the peptide and pDNA components of the lipopolyplexes. We demonstrated that both approaches to lipopolyplex targeting give reasonable transfection efficiencies, and the transfection efficiency of each lipopolyplex formulation is highly dependent on the sequence of the targeting peptide. To achieve maximum therapeutic efficiency, different peptide targeting sequences and lipopolyplex architectures should be investigated for each target cell type.

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“…Recently, quercetin has been formulated in a various nanosized formulations in order to address its conventional passive delivery and to enhance its cellular penetration into skin cells [5]. Nanoparticles are particularly useful in drug delivery for water-insoluble molecules such as chemotherapeutic drugs [6]. They have many advantages such as small size (≤100 nm), thereby, increasing absorption, ensuring bioavailability and controlled drug release making them most desirable compared to conventional drug delivery.…”

Section: Introductionmentioning

confidence: 99%

Enhancing Antioxidant Cellular Defense by Using Quercetin Loaded TiO2 Nanoparticles in Swiss 3T3 Albino Mouse Fibroblast Cells

Birinci¹,

Niazi²,

Başağa³

2017

J Nanomed Nanotechnol

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Living organisms are continuously exposed to a wide variety of oxidative radicals. Therefore, there is a constant demand for exogenous antioxidant supply. In this regard, one of these exogenous antioxidants with well established potency, quercetin has been utilized in various formulations. Yet due to its poor water solubility, its extensive applications are limited so far. In this study, TiO 2 nanoparticles (TiO 2 -NPs) were employed to improve the cellular penetration of quercetin and to maximize its antioxidant effects on swiss 3T3 albino mouse fibroblast cells. Surfaces of TiO 2 -NPs were modified with Polyethylene glycol (PEG) that enabled better dispersion and enhanced biocompatibility. Toxicity of quercetin and quercetin loaded TiO 2 NPs (QL-TiO 2 -NPs) were evaluated in terms of cell morphology and measured with cell viability assay. For an in-depth cell viability analysis, key markers of apoptosis were investigated by immunoblotting analysis. As an indicator of apoptotic cell death, cleavage of caspase 3 (Cas 3) and poly (ADP-ribose) polymerase proteins (Parp) were detected in quercetin treated cells. Antioxidant capacity of quercetin in the form of QL-TiO 2 -NPs was measured in the cells in which generation of reactive oxygen species (ROS) and superoxide was induced by pyocyanin. Quantitative ROS measurements were confirmed with confocal microscopy. Further mechanistic insight on upregulation of NF-E2 related factor 2 (NRF2) pathway via QL-TiO 2 -NPs was also provided in an effort to validate its antioxidant defense. Target enzymes of NRF2, heme oxygenase-1 (HO-1), NAD(P)H: quinone oxydoreductase1 (NQO1) and superoxide dismutase1 (SOD1) expressions were increased in the model proposed. QL-TiO 2 -NPs allowed high bioavaliability of quercetin concentration and stability in the cell with maximum antioxidant capacity against formation of ROS without any cytotoxicity. Overall, this paper sheds light on how the efficiency of quercetin in a nanosystem can serve as a safe therapeutic candidate for breaking the vicious ROS cycle in the cell. Citation: Birinci Y, Niazi JH, Basaga H (2017) Enhancing Antioxidant Cellular Defense by Using Quercetin Loaded TiO 2 Nanoparticles in Swiss 3T3Albino Mouse Fibroblast Cells. J Nanomedic Nanotechnol S8: 001. doi:10.4172/2157-7439.S8-001Page 2 of 10 J Nanomedic Nanotechnol Nanotechnology: Challenges and Perspectives in Medicine ISSN: 2157-7439 JNMNT an open access journal 3T3 albino mouse fibroblast cells. Total cellular ROS and superoxide levels in treated cells were determined and compared with those of control cells. However, quercetin in a nanosystem shows maximum antioxidant activity by triggering NRF2 pathway, upregulating phase II antioxidant enzymes, heme oxygenase-1 (HO-1), NAD(P)H: quinone oxydoreductase1 (NQO1) and superoxide dismutase1 (SOD1). In summary, our study demonstrated that quercetin loaded TiO 2 -NPs served as an effective nanosystem for delivering quercetin to swiss 3T3 albino mouse fibroblast cells in vitro and provided protection against oxida...

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Nanoparticle-mediated delivery of suicide genes in cancer therapy

Cited by 41 publications

References 184 publications

Progress in nonviral gene therapy for breast cancer and what comes next?

Progress in nonviral gene therapy for breast cancer and what comes next?

Development of lipopolyplexes for gene delivery: A comparison of the effects of differing modes of targeting peptide display on the structure and transfection activities of lipopolyplexes

Enhancing Antioxidant Cellular Defense by Using Quercetin Loaded TiO2 Nanoparticles in Swiss 3T3 Albino Mouse Fibroblast Cells

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