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Published on: December 26, 2016
Oncogenic Epidermal Growth Factor Receptor Silencing in Cervical Carcinoma Mediated by Dynamic Sugar-Benzoxaborole
Diana Diaz-Dussan1, Yi-Yang Peng1, Piyush Kumar2
1Department of Chemical and Materials Engineering, University of Alberta, Edmonton T6G 1H9, Alberta, Canada.
Abstract:
Although, various types of pharmaceuticals have been developed for cervical carcinomas, treatment with these drugs often results in a number of undesirable side effects, toxicity and multidrug resistance. Here, we aimed at modifying the genetic profiling of cancer cells by silencing the expression of the epidermal growth factor receptor (EGFR) gene. We have synthesized two kinds of RAFT-made, biocompatible, and cationic polymers for the encapsulation of silencing RNA (siRNA). This vector has a dual capability: it contains a cationic segment to complex with the siRNA and an omega-end modified with an oxaborole group via thiol-ene click chemistry that responds to the acidic tumor microenvironment. This structural innovation enables this macromolecule to interact with multiple polyplexes and release the siRNA in a mild acidic environment. A strategy that has shown enhanced gene silencing without elevating the cytotoxicity of the system, as determined by Western blot analysis. The success of this approach has afforded further interest in utilizing boron-carbohydrate interaction in the development of nonviral vectors for gene therapy.
Insights
Researchers developed novel polymers to deliver gene-silencing RNA (siRNA) targeting the epidermal growth factor receptor (EGFR) in cervical cancer. This approach enhances gene silencing and reduces toxicity, offering a promising new avenue for cancer gene therapy.
Area of Science:
- Biomaterials Science
- Cancer Gene Therapy
- Polymer Chemistry
Background:
- Cervical cancer treatments face challenges including side effects, toxicity, and multidrug resistance.
- Targeting the epidermal growth factor receptor (EGFR) offers a potential strategy for cancer therapy.
- Developing effective and safe delivery systems for gene-silencing agents is crucial.
Purpose of the Study:
- To synthesize novel RAFT-made, biocompatible, cationic polymers for siRNA delivery.
- To engineer a polymer vector with an oxaborole group responsive to acidic tumor microenvironments.
- To evaluate the efficacy and cytotoxicity of the developed vector for EGFR gene silencing in cancer cells.
Main Methods:
- Synthesis of RAFT-made cationic polymers with oxaborole modification via thiol-ene click chemistry.
- Encapsulation of small interfering RNA (siRNA) targeting the EGFR gene.
- Assessment of gene silencing efficacy using Western blot analysis.
- Evaluation of system cytotoxicity.
Main Results:
- Successful synthesis of dual-capability polymer vectors capable of complexing siRNA.
- Demonstrated siRNA release in a mild acidic environment, characteristic of tumor microenvironments.
- Achieved enhanced EGFR gene silencing without significant increase in cytotoxicity.
- Validated the potential of boron-carbohydrate interactions in nonviral vector development.
Conclusions:
- Novel RAFT-made polymers effectively deliver siRNA for EGFR gene silencing in cancer cells.
- The oxaborole modification enables environment-specific siRNA release, enhancing therapeutic potential.
- This boron-carbohydrate-based strategy presents a promising, less cytotoxic approach for nonviral gene therapy in cervical cancer.
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