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Updated: Dec 4, 2025
Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
A combination of LightOn gene expression system and tumor microenvironment-responsive nanoparticle delivery system
Xinyu Hou1,2, Chenting Shou2, Muye He2
1Shanghai Key Laboratory of New Drug Design, East China University of Science and Technology, Shanghai 200237, China.
Abstract:
A light-switchable transgene system called LightOn gene expression system could regulate gene expression with a high on/off ratio under blue light, and have great potential for spatiotemporally controllable gene expression. We developed a nanoparticle drug delivery system (NDDS) to achieve tumor microenvironment-responsive and targeted delivery of diphtheria toxin A (DTA) fragment-encoded plasmids to tumor sites. The expression of DTA was induced by exposure to blue light. Nanoparticles composed of polyethylenimine and vitamin E succinate linked by a disulfide bond, and PEGylated hyaluronic acid modified with RGD peptide, accumulated in tumor tissues and were actively internalized into 4T1 cells via dual targeting to CD44 and α v β 3 receptors. The LightOn gene expression system was able to control target protein expression through regulation of the intensity or duration of blue light exposure. In vitro studies showed that light-induced DTA expression reduced 4T1 cell viability and induced apoptosis. Furthermore, the LightOn gene expression system enabled spatiotemporal control of the expression of DTA in a mouse 4T1 tumor xenograft model, which resulted in excellent antitumor effects, reduced tumor angiogenesis, and no systemic toxicity. The combination of the LightOn gene expression system and NDDS may be an effective strategy for treatment of breast cancer.
Insights
A novel nanoparticle drug delivery system combined with a light-switchable gene expression system effectively targets breast cancer tumors. Blue light precisely controls therapeutic gene expression, reducing tumor growth and toxicity.
Area of Science:
- Biotechnology
- Nanomedicine
- Molecular Biology
Background:
- Gene expression regulation is crucial for targeted therapies.
- Developing precise control over therapeutic gene delivery remains a challenge.
- Nanoparticle drug delivery systems (NDDS) offer potential for targeted cancer treatment.
Purpose of the Study:
- To develop a light-inducible nanoparticle drug delivery system for targeted breast cancer therapy.
- To evaluate the efficacy of the LightOn gene expression system for spatiotemporal control of diphtheria toxin A (DTA) expression.
- To assess the antitumor effects and safety of the combined system in a preclinical breast cancer model.
Main Methods:
- Engineered nanoparticles encapsulating DTA-encoding plasmids with dual targeting (CD44 and αvβ3 receptors).
- Utilized the LightOn gene expression system for blue light-inducible DTA expression.
- Evaluated *in vitro* cytotoxicity in 4T1 cells and *in vivo* antitumor efficacy in a 4T1 tumor xenograft mouse model.
Main Results:
- Nanoparticles demonstrated accumulation and active internalization into 4T1 cells.
- Blue light exposure precisely controlled DTA expression, reducing 4T1 cell viability and inducing apoptosis *in vitro*.
- The combined system achieved significant antitumor effects, reduced tumor angiogenesis, and showed no systemic toxicity in the mouse model.
Conclusions:
- The combination of the LightOn gene expression system and NDDS provides a spatiotemporally controlled and targeted approach for breast cancer therapy.
- This strategy offers a promising platform for cancer treatment with enhanced efficacy and reduced side effects.
- Precise control over gene expression via external stimuli like light represents a significant advancement in nanomedicine for oncology.
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