Related Experiment Video
Updated: Aug 6, 2025
Uptake of New Lipid-coated Nanoparticles Containing Falcarindiol by Human Mesenchymal Stem Cells
Published on: February 9, 2019
Intracellular delivery of bacterial effectors for cancer therapy using biodegradable lipid nanoparticles
Wenting Li1,2, Leihou Shao1,2, Ji Liu1,2
1Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
Abstract:
Bacterial effector proteins are virulence factors that are secreted and mediate orthogonal post-translational modifications of proteins that are not found naturally in mammalian systems. They hold great promise for developing biotherapeutics by regulating malignant cell signaling in a specific and targeted manner. However, delivering bacterial effectors into disease cells poses a significant challenge to their therapeutic potential. In this study, we report on the design of a combinatorial library of bioreducible lipid nanoparticles containing disulfide bonds for highly efficient bacterial effector delivery and potential cancer therapy. A leading lipid, PPPDA-O16B, identified from the library, can encapsulate and deliver DNA plasmids into cells. The gene cargo is released in response to the reductive cellular environment that is upregulated in cancer cells, leading to enhanced gene delivery and protein expression efficiency. Furthermore, we demonstrate that PPPDA-O16B can deliver the bacterial effector protein, DUF5, to degrade mutant RAS and inactivate downstream MAPK signaling cascades to suppress cancer cell growth in vitro and in tumor-bearing mouse xenografts. This strategy of delivering bacterial effectors using biodegradable lipid nanoparticles can be expanded for cancer cell signaling regulation and antitumor studies.
Insights
Researchers developed bioreducible lipid nanoparticles to deliver bacterial effector proteins for cancer therapy. This novel delivery system effectively targets cancer cells, degrades mutant RAS, and suppresses tumor growth, offering a promising new avenue for cancer treatment.
Area of Science:
- Biotechnology
- Molecular Biology
- Cancer Research
Background:
- Bacterial effector proteins offer therapeutic potential for regulating cancer cell signaling.
- Efficient delivery of these proteins into diseased cells remains a significant challenge for biotherapeutics.
Purpose of the Study:
- To design and evaluate bioreducible lipid nanoparticles for enhanced delivery of bacterial effector proteins.
- To assess the therapeutic efficacy of bacterial effector delivery in cancer models.
Main Methods:
- A combinatorial library of bioreducible lipid nanoparticles was synthesized and screened.
- A lead lipid, PPPDA-O16B, was identified for its ability to encapsulate and deliver DNA plasmids.
- The delivery system was tested for its ability to deliver the bacterial effector DUF5 to degrade mutant RAS and inhibit MAPK signaling.
- In vitro and in vivo (mouse xenograft) studies were conducted to evaluate cancer cell growth suppression.
Main Results:
- The identified lipid PPPDA-O16B efficiently encapsulated and delivered DNA plasmids into cells.
- Gene cargo release was triggered by the reductive cellular environment upregulated in cancer cells, enhancing delivery and expression.
- PPPDA-O16B successfully delivered the bacterial effector DUF5, leading to mutant RAS degradation and MAPK pathway inactivation.
- Significant suppression of cancer cell growth was observed both in vitro and in tumor-bearing mouse xenografts.
Conclusions:
- Bioreducible lipid nanoparticles, exemplified by PPPDA-O16B, provide a highly efficient strategy for bacterial effector delivery.
- This approach enables targeted cancer cell signaling regulation and demonstrates potent antitumor effects.
- The developed nanoparticle system holds promise for broader applications in cancer therapy and antitumor research.
