Magnetic Nanoparticles as a Component of Peptide-Based DNA Delivery System for Suicide Gene Therapy of Uterine Leiomyoma

Shtykalova, Sofia; Egorova, Anna; Maretina, Marianna; Baranov, Vladislav S; Kiselev, Anton

doi:10.3390/bioengineering9030112

Cited by 7 publications

(5 citation statements)

References 38 publications

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“…Large aggregates of polyplexes have the potential to interact with cell membranes and, as a result, some of these complexes can be taken up by the cells. Similar findings were obtained in our previous study of peptide-based polyplexes combined with anionic magnetic nanoparticles [ 22 ]. Another important discovery emerged from the transfection studies.…”

Section: Resultssupporting

confidence: 91%

“…During intercellular interactions, phosphorylated ganciclovir is transferred to neighboring cells, and this phenomenon is closely linked to this process [ 16 ]. It is important to note that the suicide gene therapy that uses the HSV-TK/GCV system has already been employed in gene therapy research of uterine leiomyoma [ 7 , 10 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

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Serum-Resistant Ternary DNA Polyplexes for Suicide Gene Therapy of Uterine Leiomyoma

Egorova,

Shtykalova,

Maretina

et al. 2023

IJMS

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Uterine leiomyoma (UL) is a prevalent benign tumor in women that frequently gives rise to a multitude of reproductive complications. The use of suicide gene therapy has been proposed as a highly promising method for treating UL. To achieve successful gene therapy, it is essential to develop carriers that can efficiently transport nucleic acids into targeted cells and tissues. The instability of polyplexes in blood and other biological fluids is a crucial factor to consider when using non-viral carriers. In this study, we present serum-resistant and cRGD-modified DNA complexes for targeted delivery genes to UL cells. Ternary polyplexes were formed by incorporating cystine-cross-linked polyglutamic acid modified with histidine residues. We employed two techniques in the production of cross-linked polyanionic coating: matrix polymerization and oxidative polycondensation. In this study, we investigated the physicochemical properties of ternary DNA complexes, including the size and zeta-potential of the nanoparticles. Additionally, we evaluated cellular uptake, toxicity levels, transfection efficiency and specificity in vitro. The study involved introducing the HSV-TK gene into primary UL cells as a form of suicide gene therapy modeling. We have effectively employed ternary peptide-based complexes for gene delivery into the UL organtypic model. By implementing in situ suicide gene therapy, the increase in apoptosis genes expression was detected, providing conclusive evidence of apoptosis occurring in the transfected UL tissues. The results of the study strongly suggest that the developed ternary polyplexes show potential as a valuable tool in the implementation of suicide gene therapy for UL.

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Section: Resultssupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Serum-Resistant Ternary DNA Polyplexes for Suicide Gene Therapy of Uterine Leiomyoma

Egorova,

Shtykalova,

Maretina

et al. 2023

IJMS

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“…Previously, we developed several gene delivery systems based on matrix polymerized or polycondensed crosslinking peptides modified with iRGD or cycloRGD ligands [ 33 , 53 , 54 ]. Developed non-viral carriers were used for HSV-TK gene transfer to the cellular model of uterine leiomyoma and suicide gene therapy effects were accessed by different methods including an alamarBlue assay.…”

Section: Resultsmentioning

confidence: 99%

“…According to alamarBlue assay data the most pronounced therapeutic effect—elimination of 57% UL cells was registered for R6p-cRGD/pPTK1 polyplexes; however, the application of RGD-R6p-0,75/pPTK1 and RGD1-R6/pPTK polyplexes was not much less efficient—53% and 46%, respectively [ 33 , 53 ]. In addition, it should be noted that a combination of R6p-cRGD/pPTK1 polyplexes with magnetic nanoparticles decreased the therapeutic effect—only 33% of UL cells were eliminated; however, transfection time was greatly decreased [ 54 ]. Thus, it can be concluded that the application of reducible polycondensed R6p carrier has a major impact on the transfection efficacy and HSV1-TK-mediated therapeutic effect.…”

Section: Resultsmentioning

confidence: 99%

Peptide-Based Nanoparticles for αvβ3 Integrin-Targeted DNA Delivery to Cancer and Uterine Leiomyoma Cells

et al. 2022

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Uterine leiomyoma is the most common benign tumor of the reproductive system. Current therapeutic options do not simultaneously meet the requirements of long-term efficiency and fertility preservation. Suicide gene delivery can be proposed as a novel approach to uterine leiomyoma therapy. Non-viral vehicles are an attractive approach to DNA delivery for gene therapy of both malignant and benign tumors. Peptide-based vectors are among the most promising candidates for the development of artificial viruses, being able to efficiently cross barriers of DNA transport to cells. Here we described nanoparticles composed of cysteine-crosslinked polymer and histidine-arginine-rich peptide modified with iRGD moiety and characterized them as vehicles for plasmid DNA delivery to pancreatic cancer PANC-1 cells and the uterine leiomyoma cell model. Several variants of nanoparticles were formulated with different targeting ligand content. The physicochemical properties that were studied included DNA binding and protection, interaction with polyanions and reducing agents, size, structure and zeta-potential of the peptide-based nanoparticles. Cytotoxicity, cell uptake and gene transfection efficiency were assessed in PANC-1 cells with GFP and LacZ-encoding plasmids. The specificity of gene transfection via αvβ3 integrin binding was proved in competitive transfection. The therapeutic potential was evaluated in a uterine leiomyoma cell model using the suicide gene therapy approach. The optimal formulation was found to be at the polyplex with the highest iRGD moiety content being able to transfect cells more efficiently than control PEI. Suicide gene therapy using the best formulation resulted in a significant decrease of uterine leiomyoma cells after ganciclovir treatment. It can be concluded that the application of iRGD-modified peptide-based nanoparticles has a high potential for cellular delivery of DNA therapeutics in favor of uterine leiomyoma gene therapy.

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“…It reduces transfection time and improves delivery of pDNA encoding thymine kinase gene for the herpes simplex virus type I (HSV-1). Therefore, it shows a potential nonviral-based approach for the treatment of uterine leiomyoma …”

Section: Biomedical Applications Of Nanopeptidesmentioning

confidence: 99%

Functionalized Peptide-Based Nanoparticles for Targeted Cancer Nanotherapeutics: A State-of-the-Art Review

et al. 2022

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Cancer mortality is increasing at an alarming rate across the globe. Albeit, many therapeutics are available commercially, they are not effective and have no cure up to today. Moreover, the knowledge gap in cancer therapy persists, representing a potential blind spot for the innovation of effective anticancer therapeutics. This review presents an update on current advancements in nanopeptide therapeutics. Herein, a detailed exploration of peptide-functionalized nanoparticles for the development of nanotherapeutics was carried out. Different approaches that include self-assembly nanostructures, solid phase peptide synthesis, ligand exchange, chemical reduction, and conjugation methods for assembling peptides for functionalizing nanodrugs are also highlighted. An outlook on biomedical applications is also reviewed. Additionally, a comprehensive discussion on targeted cancer cell therapy and mechanism of action are provided. The present review reflects the functional novelty of nanodrugs to improve stability, accessibility, bioavailability, and specificity toward cancerous cells. Finally, it summarizes the current challenges and future perspectives on the formulation of these nanodrugs.

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Magnetic Nanoparticles as a Component of Peptide-Based DNA Delivery System for Suicide Gene Therapy of Uterine Leiomyoma

Cited by 7 publications

References 38 publications

Serum-Resistant Ternary DNA Polyplexes for Suicide Gene Therapy of Uterine Leiomyoma

Serum-Resistant Ternary DNA Polyplexes for Suicide Gene Therapy of Uterine Leiomyoma

Peptide-Based Nanoparticles for αvβ3 Integrin-Targeted DNA Delivery to Cancer and Uterine Leiomyoma Cells

Functionalized Peptide-Based Nanoparticles for Targeted Cancer Nanotherapeutics: A State-of-the-Art Review

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