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Nonviral cancer gene therapy: Delivery cascade and vector nanoproperty integration
Zhuxian Zhou1, Xiangrui Liu1, Dingcheng Zhu1
1Center for Bionanoengineering and Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Zheda Road 38, 310027 Hangzhou, China.
Abstract:
Gene therapy represents a promising cancer treatment featuring high efficacy and limited side effects, but it is stymied by a lack of safe and efficient gene-delivery vectors. Cationic polymers and lipid-based nonviral gene vectors have many advantages and have been extensively explored for cancer gene delivery, but their low gene-expression efficiencies relative to viral vectors limit their clinical translations. Great efforts have thus been devoted to developing new carrier materials and fabricating functional vectors aimed at improving gene expression, but the overall efficiencies are still more or less at the same level. This review analyzes the cancer gene-delivery cascade and the barriers, the needed nanoproperties and the current strategies for overcoming these barriers, and outlines PEGylation, surface-charge, size, and stability dilemmas in vector nanoproperties to efficiently accomplish the cancer gene-delivery cascade. Stability, surface, and size transitions (3S Transitions) are proposed to resolve those dilemmas and strategies to realize these transitions are comprehensively summarized. The review concludes with a discussion of the future research directions to design high-performance nonviral gene vectors.
Insights
Developing safe and efficient nonviral gene vectors for cancer gene therapy is crucial. This review proposes "3S Transitions" (stability, surface, size) to overcome current vector limitations and enhance gene delivery efficiency.
Area of Science:
- Biotechnology
- Nanomedicine
- Oncology
Background:
- Gene therapy offers a promising cancer treatment with high efficacy and minimal side effects.
- Current nonviral gene vectors face challenges in achieving sufficient gene-expression efficiency for clinical translation.
- Existing efforts to improve vector performance have yielded limited success.
Purpose of the Study:
- To analyze the barriers in the cancer gene-delivery cascade.
- To identify essential nanoproperties for effective gene vectors.
- To propose strategies for overcoming current limitations in nonviral vector design.
Main Methods:
- Comprehensive review of existing literature on cancer gene delivery.
- Analysis of nanoproperty dilemmas including PEGylation, surface charge, size, and stability.
- Introduction of the "3S Transitions" (stability, surface, size) concept.
Main Results:
- Identified key barriers in the cancer gene-delivery cascade.
- Outlined dilemmas associated with vector nanoproperties (PEGylation, surface charge, size, stability).
- Proposed "3S Transitions" as a framework to address these dilemmas.
Conclusions:
- "3S Transitions" offer a novel approach to designing high-performance nonviral gene vectors.
- Strategies for realizing these transitions are summarized.
- Future research should focus on developing advanced nonviral vectors for improved cancer gene therapy.
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