Graphene oxide–hydroxyapatite nanocomposites effectively deliver HSV-TK suicide gene to inhibit human breast cancer growth

Gene therapy with herpes simplex virus thymidine kinase gene (HSV-TK), which is also known as “suicide” gene therapy, is effective in various tumor models. The lack of a safe and efficient gene delivery system has become a major obstacle to “suicide” gene therapy. In this study, the cytotoxicity and transfection efficiency of graphene oxide–hydroxyapatite (GO–Hap) were analyzed by MTS and flow cytometry, respectively. A series of assays were performed to evaluate the effects of GO–HAp/p-HRE/ERE-Sur-TK combined with ganciclovir treatment on growth of human breast normal and cancer cells. The results showed that GO–HAp nanocomposites effectively transfected cells with minimum toxicity. GO–HAp/p-HRE/ERE-Sur-TK combined with ganciclovir treatment inhibited the proliferation and induced cell apoptosis in cancer cells, while the cytotoxic effects are tolerable in normal breast cells. We conclude that the GO–HAp nanocomposites have significant potential as a gene delivery vector for cancer therapy.

Download Full-text

The war against cancer: Suicide gene therapy

Advances in Modern Oncology Research ◽

10.18282/amor.v2.i3.103 ◽

2016 ◽

Vol 2 (3) ◽

pp. 139

Author(s):

Muzeyyen Izmirli ◽

Dilara Sonmez ◽

Bulent Gogebakan

Keyword(s):

Gene Therapy ◽

Cytochrome P450 ◽

Side Effects ◽

Cancer Cells ◽

Thymidine Kinase ◽

Viral Vectors ◽

Suicide Gene ◽

Suicide Gene Therapy ◽

Kinase Gene ◽

Cancer Society

<p>The National Cancer Institute and the American Cancer Society announced that 1.6 million new cancer cases are projected to occur in the USA in 2016. One of the most innovative approaches against cancer is suicide gene therapy, in which suicide-inducing transgenes are introduced into cancer cells. When cancer treatments target the total elimination of tumor cells, there will be no side effects for normal cells. Cancer tissues are targeted through various targeted transport methods, followed by tissue-specific enzymes converting a systemically suitable prodrug into an active drug in the tumor. Suicidal genes are delivered by transporters, such as viral and non-viral vectors, into cancer cells. Suicide gene therapeutic strategies currently pursued are herpes simplex virus thymidine kinase gene with prodrug ganciclovir, cytosine deaminase gene, carboxyl esterase/irinotecan, varicella zoster virus thymidine kinase/6-methoxypurine arabinonucleoside, nitroreductase Nfsb/5-(aziridin-1-yl)-2,4-dinitrobenzamide, carboxypeptidase G2/4-[(2-chloroethyl)(2- mesyloxyethyl)amino]benzoyl-L-glutamic acid, cytochrome p450-isofosfamide, and cytochrome p450-cyclophosphamide. The goal of this review is to summarize the different suicide gene systems and gene delivery vectors addressed to cancer cells, with a particular emphasis on recently developed systems. Finally, we briefly describe the advantageous clinical applications and potential side effects of suicide gene therapy. </p>

Download Full-text

Development of iRGD-Modified Peptide Carriers for Suicide Gene Therapy of Uterine Leiomyoma

Pharmaceutics ◽

10.3390/pharmaceutics13020202 ◽

2021 ◽

Vol 13 (2) ◽

pp. 202

Author(s):

Anna Egorova ◽

Sofia Shtykalova ◽

Alexander Selutin ◽

Natalia Shved ◽

Marianna Maretina ◽

...

Keyword(s):

Gene Therapy ◽

Uterine Leiomyoma ◽

Transfection Efficiency ◽

Chemical Properties ◽

Suicide Gene ◽

Suicide Gene Therapy ◽

Benign Tumors ◽

Αvβ3 Integrin ◽

Peptide Carrier ◽

Plasmid Delivery

Uterine leiomyoma (UL) is one of the most common benign tumors in women that often leads to many reproductive complications. Suicide genetherapy was suggested as a promising approach for UL treatment. In the present study, we describe iRGD ligand-conjugated cysteine-rich peptide carrier RGD1-R6 for targeted DNA delivery to αvβ3 integrin-expressing primary UL cells. The physico-chemical properties, cytotoxicity, transfection efficiency and specificity of DNA/RGD1-R6 polyplexes were investigated. TheHSV-1thymidine kinase encoding plasmid delivery to PANC-1pancreatic carcinoma cells and primary UL cells resulted in significant suicide gene therapy effects. Subsequent ganciclovir treatment decreased cells proliferative activity, induced of apoptosis and promoted cells death.The obtained results allow us to concludethatthe developed RGD1-R6 carrier can be considered a promising candidate for suicide gene therapy of uterine leiomyoma.

Download Full-text