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Targeted Gene Delivery Therapies for Cervical Cancer.

ABSTRACT: Despite being largely preventable through early vaccination and screening strategies, cervical cancer is the most common type of gynecological malignancy worldwide and constitutes one of the leading causes of cancer deaths in women. Patients with advanced or recurrent disease have a very poor prognosis; hence, novel therapeutic modalities to improve clinical outcomes in cervical malignancy are needed. In this regard, targeted gene delivery therapy is presented as a promising approach, which leads to the development of multiple strategies focused on different aspects. These range from altered gene restoration, immune system potentiation, and oncolytic virotherapy to the use of nanotechnology and the design of improved and enhanced gene delivery systems, among others. In the present manuscript, we review the current progress made in targeted gene delivery therapy for cervical cancer, the advantages and drawbacks and their clinical application. At present, multiple targeted gene delivery systems have been reported with encouraging preclinical results. However, the translation to humans has not yet shown a significant clinical benefit due principally to the lack of efficient vectors. Real efforts are being made to develop new gene delivery systems, to improve tumor targeting and to minimize toxicity in normal tissues.

SUBMITTER: Ayen A

PROVIDER: S-EPMC7281413 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Targeted Gene Delivery Therapies for Cervical Cancer.

Áyen Ángela Á Jiménez Martínez Yaiza Y Boulaiz Houria H

Cancers 20200521 5

Despite being largely preventable through early vaccination and screening strategies, cervical cancer is the most common type of gynecological malignancy worldwide and constitutes one of the leading causes of cancer deaths in women. Patients with advanced or recurrent disease have a very poor prognosis; hence, novel therapeutic modalities to improve clinical outcomes in cervical malignancy are needed. In this regard, targeted gene delivery therapy is presented as a promising approach, which lead ...[more]

PMID: 32455616

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Project description:ObjectivesThe success of prosthetic vascular grafts in the management of peripheral arterial disease is frequently limited by the development of anastomotic neointimal hyperplasia (ANIH), with the host response to prosthetic grafts beginning soon after implantation. To address this, we combine a platform of polyethylene terephthalate (PET) fabric with an applied cryogel layer containing biologic agents to create a bioactive prosthetic graft system, with the ability to deliver therapeutics targeting modulators of the ANIH-associated transcriptome response, along with antithrombotic agents.MethodsHybrid graft materials were synthesized by cryopolymerization of methacrylated alginate and heparin onto electrospun (ePET), knitted PET (kPET), or woven PET (wPET). Arg-Gly-Asp (RGD) peptides were added to increase cell adhesion. Scanning electron microscopy (SEM) was used to study the microstructure at 1 day, and 2, 4, and 8 weeks. Physical properties such as swelling ratio, pore connectivity, shape recovery, and stiffness were evaluated. Human aortic endothelial cell (HAoEC) adherence was visualized using confocal microscopy after 24 hours and proliferation was evaluated with a resazurin-based assay for 7 days. Confocal microscopy was used to assess delivery of adeno-associated virus (AAV-GFP) after incubation of hybrid grafts with HAoECs. Heparin activity of the materials was measured using an anti-Xa assay.ResultsSEM demonstrated large interconnected pores throughout the entire structure for all graft types, with minimal degradation of the cryogel after 8 weeks. Hybrid materials showed a trend towards increased shape recovery, increased stiffness, decreased swelling ratio, and no difference in pore connectivity. HAoECs incorporated, adhered, and proliferated over 7 days on all materials. HAoECs were successfully transduced with AAV-GFP from the hybrid graft materials. Anti-Xa assay confirmed continued activity of heparin from all materials for over 7 days.ConclusionsWe have developed a bioactive prosthetic graft system with a cryogel coating capable of delivering biologic agents with antithrombotic activity. By applying the cryogel and selected agents onto PET prior to graft implantation, this study sets the stage for the system to be individualized and tailored to the patient, with bioengineering and targeted gene therapy strategies dovetailing to create an improved prosthetic graft adaptable to emerging knowledge and technologies.

Dataset Information

Targeted Gene Delivery Therapies for Cervical Cancer.

Publications

Targeted Gene Delivery Therapies for Cervical Cancer.

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