Degradable Polyethylenimine-Based Gene Carriers for Cancer Therapy
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Published on: August 6, 2019
Hu-Lin Jiang1, Mohammad Ariful Islam2, Lei Xing1
1State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, 210009, China.
Abstract:
Gene therapy using recombinant DNA or gene silencing using siRNA have become a prominent area of research in cancer therapy. However, their use in clinical applications is limited due to overall safety concerns and suboptimal efficacy. Although non-viral vectors such as polycationic polymers do not offer the same level of transfection efficiency as their viral counterparts, they still demonstrate immense potential as alternatives to viral vectors, given their versatility, low immunogenicity, ease of large-scale production, and ability to accelerate gene transfer with well-designed delivery platforms. Among these polymers, polyethylenimine (PEI) is considered a state-of-the-art gene carrier, owing to its ability to improve gene transfer capacity and intracellular delivery. Nonetheless, PEI suffers from the critical shortcoming of non-degradability that can lead to severe cytotoxic effects, despite the fact that the level of this toxicity decreases with molecular weight (MW). As a result, a considerable amount of effort has been devoted to designing low-MW PEI derivatives with degradable linkages. This review will categorize the recent advances in these degradable PEI derivatives based on their degradable chemistries, including ester, disulfide, imine, carbamate, amide, and ketal linkages, and summarize their application in gene therapies against various major cancer malignancies.
Insights
Researchers are developing degradable polyethylenimine (PEI) derivatives for safer and more effective gene therapy in cancer treatment. These modified non-viral vectors aim to overcome the limitations of traditional PEI, enhancing gene delivery while minimizing toxicity.
Area of Science:
- Biomedical Engineering
- Molecular Biology
- Oncology
Background:
- Gene therapy and gene silencing show promise for cancer treatment but face safety and efficacy challenges.
- Non-viral vectors, particularly polycationic polymers like polyethylenimine (PEI), offer advantages over viral vectors in gene delivery.
- Non-degradability of conventional PEI leads to cytotoxicity, limiting its clinical application.
Purpose of the Study:
- To review recent advancements in degradable PEI derivatives for gene therapy.
- To categorize these derivatives based on their degradable linkages.
- To summarize their therapeutic potential against various cancers.
Main Methods:
- Review of scientific literature on degradable PEI derivatives.
- Categorization of PEI derivatives by chemical linkage (ester, disulfide, imine, carbamate, amide, ketal).
- Summary of applications in preclinical cancer gene therapy models.
Main Results:
- Development of various degradable PEI derivatives with different chemical linkages.
- Demonstrated potential of these derivatives to improve gene transfer and reduce PEI-induced cytotoxicity.
- Successful application of some derivatives in targeting diverse cancer types.
Conclusions:
- Degradable PEI derivatives represent a promising strategy to enhance the safety and efficacy of non-viral gene therapy for cancer.
- Tailoring degradable linkages in PEI offers a versatile platform for optimizing gene delivery systems.
- Further research into these advanced materials could lead to novel cancer treatment modalities.
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