Development of New Gonadotropin-Releasing Hormone-Modified Dendrimer Platforms with Direct Antiproliferative and Gonadotropin Releasing Activity

Varamini, Pegah; Rafiee, Amirreza; Giddam, Ashwini Kumar; Mansfeld, Friederike M.; Steyn, Frederik J.; Tóth, István

doi:10.1021/acs.jmedchem.6b01771

Cited by 7 publications

(7 citation statements)

References 40 publications

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“…It was noted in this study that the MCF-7 cell line lost its sensitivity to both lytic conjugates when steroids were removed from the medium (Leuschner et al 2003) indicating the role of steroids in the antitumor effects of the conjugates. The role of steroids in the direct antiproliferative activity of GnRH analogs was also confirmed in some other studies (Goodwin et al 2015, Varamini et al 2017.…”

Section: Gnrh-lytic Peptide Conjugatessupporting

confidence: 64%

New drug delivery strategies targeting the GnRH receptor in breast and other cancers

Ghaly

Varamini

2021

Endocrine-Related Cancer

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Cancer is the uncontrolled division of abnormal cells in a specific organ. Globally, about 1 in 6 deaths is due to cancer. Despite the plethora of research being undertaken worldwide to find a cure for cancer, it remains a significant challenge. Cancer targeting via agents designed to interfere with some specifically or highly expressed molecules in cancer cells has been a shift in the treatment of various forms of cancers. The development of drug delivery systems, specifically to cancer cells, is a common approach that succeeded in increasing the efficacy and reducing the side effects of different anticancer agents. Gonadotropin-releasing hormone (GnRH) is a naturally occurring hormone with receptors overexpressed in many types of cancers related or unrelated to the reproductive system. Several drug delivery systems were developed using GnRH derivatives as targeting agents. In this review, we first discuss the role of GnRH and its receptors in cancer. Then, we provide a detailed insight into different delivery systems developed using GnRH derivatives as targeting agents in various types of GnRH receptor overexpressing cancers. Some promising findings from these studies indicate that GnRH receptor targeting is a potential strategy to efficiently guide anticancer therapeutics, diagnostic agents, and nucleic acids directly to cancer cells. Lastly, some limitations of the current research and suggestions for more successful outcomes in clinical trials of these delivery systems are highlighted.

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Section: Gnrh-lytic Peptide Conjugatessupporting

confidence: 64%

New drug delivery strategies targeting the GnRH receptor in breast and other cancers

Ghaly

Varamini

2021

Endocrine-Related Cancer

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“…Dendrimers with polyvalent structures, first developed in the 1980s [15,16], have been widely regarded as useful carriers for small molecular drugs and gene delivery [17,18]. By integrating the merits of dendrimers with bioactive peptides, peptide-decorated dendrimers (PDDs) have been extensively fabricated to generate vaccines [19,20,21,22,23,24], antiviral agents [25,26], and antitumor therapeutics [27,28,29,30,31,32] due to their multivalency effects. In particular, dendrimeric peptides have shown interesting properties for enhancing overall binding affinity and specificity compared with monovalent ligands.…”

Section: Introductionmentioning

confidence: 99%

Blockade of Human α7 Nicotinic Acetylcholine Receptor by α-Conotoxin ImI Dendrimer: Insight from Computational Simulations

Liang

Zhang

et al. 2019

Marine Drugs

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Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that are involved in fast synaptic transmission and mediated physiological activities in the nervous system. α-Conotoxin ImI exhibits subtype-specific blockade towards homomeric α7 and α9 receptors. In this study, we established a method to build a 2×ImI-dendrimer/h (human) α7 nAChR model, and based on this model, we systematically investigated the molecular interactions between the 2×ImI-dendrimer and hα7 nAChR. Our results suggest that the 2×ImI-dendrimer possessed much stronger potency towards hα7 nAChR than the α-ImI monomer and demonstrated that the linker between α-ImI contributed to the potency of the 2×ImI-dendrimer by forming a stable hydrogen-bond network with hα7 nAChR. Overall, this study provides novel insights into the binding mechanism of α-ImI dendrimer to hα7 nAChR, and the methodology reported here opens an avenue for the design of more selective dendrimers with potential usage as drug/gene carriers, macromolecular drugs, and molecular probes.

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“…Newly developed dendrimers contain various GnRH copies attached to a lipid nucleus derived from lipid A, which is composed of 2-amino-d, l-hexadecanoic acid, and Th and B immunogenic epitopes. The immunization of mice with this molecule produced high anti-GnRH antibody responses, and the dendritic cells stimulation (53). This and other chemical modifications to peptides, like cyclization, glycosilation, and lipidation, are viable alternatives to modulate their physical and chemical properties and increase their bioavailability orally.…”

Section: Long -Term Immunity and Vaccine Delivery Systems: The Two Great Research Challenges In Immunocontraceptionmentioning

confidence: 99%

Contraception and immunocastration vaccines. Use in veterinary medicine

Campal-Espinosa¹,

Junco-Barranco²,

Fuentes-Aguilar³

et al. 2020

Rev Colombiana Cienc Anim. RECIA

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Globally, development and application of vaccines to control fertility in animals is growing relentlessly. Their productive benefits to animal management and welfare are corroborated, while improvement in public perception on their positive impact. This paper reviews current developments in this area, particularly, immunocastration vaccines, upon assessment of application results in recent years. Main targets of these vaccines are proteins of the zona pellucida, the structural proteins of spermatozoa as well as the sexual hormones. Various GnRH-based vaccines with proven effectiveness and efficiency for immunocastration of males and fertility control in females are commercially available today. However, issues like a reduction in the number of immunizations, achieving of increased immunogenicity, and the development new formulations to facilitate the application and release of vaccines in the wide diversity of the animal habitats and in the different conditions of animal husbandry, should be addressed. Fertility control relied on methods that guarantee productive efficiency and animal welfare is an incessant need of modern veterinary medicine practice.

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Development of New Gonadotropin-Releasing Hormone-Modified Dendrimer Platforms with Direct Antiproliferative and Gonadotropin Releasing Activity

Cited by 7 publications

References 40 publications

New drug delivery strategies targeting the GnRH receptor in breast and other cancers

New drug delivery strategies targeting the GnRH receptor in breast and other cancers

Blockade of Human α7 Nicotinic Acetylcholine Receptor by α-Conotoxin ImI Dendrimer: Insight from Computational Simulations

Contraception and immunocastration vaccines. Use in veterinary medicine

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