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Reactive oxygen species (ROS)-responsive nanomedicine for RNAi-based cancer therapy
Yang Li1, Hongzhen Bai, Hebin Wang
1Institute of Chemical Biology and Pharmaceutical Chemistry, Department of Chemistry, Zhejiang University, Hangzhou 310028, P. R. China. tangguping@zju.edu.cn.
Abstract:
Although much effort has been dedicated to the development of efficient siRNA delivery for cancer therapy, delivery nanomaterials that can particularly respond to reactive oxygen species (ROS), which are overproduced in the tissue and mitochondria of cancer cells, are still rare for the clinical translation of RNA interference (RNAi)-based therapy. To this end, we developed a ROS-responsive boronic vehicle with a lipid envelope for systemic vascular endothelial growth factor (VEGF) siRNA delivery so as to improve RNAi cancer therapy. We found that the efficiency of siRNA delivery largely relied on the ROS responsiveness of the carrier we have developed to mediate timely siRNA release, the PEG-functionalized lipid layer to shield the surface charge of polyplexes as well as the ability of the phenylboronic moiety to stabilize siRNA. The unique carrier nanostructure provides the efficient systemic transportation of siRNA to the tumor site for effective knockdown of the VEGF, which resulted in a significant antiangiogenesis effect and the effective inhibition of tumor growth in vivo. The current study defines a new systemic delivery strategy for siRNA by cooperatively integrating multifunctional lipid coatings with the ROS-responsive boronic polymer, which may potentially benefit RNAi-based therapy in the dawning era of precision nanomedicine for cancer therapy.
Insights
Researchers developed a novel ROS-responsive nanocarrier for targeted siRNA delivery in cancer therapy. This system effectively delivers vascular endothelial growth factor siRNA, inhibiting tumor growth and offering a promising strategy for RNA interference-based treatments.
Area of Science:
- Nanomedicine
- Biotechnology
- Cancer Therapy
Background:
- Efficient siRNA delivery remains a challenge for RNA interference (RNAi) cancer therapy.
- Targeted delivery systems responsive to the tumor microenvironment, specifically reactive oxygen species (ROS), are scarce.
- Overproduction of ROS in cancer cells presents an opportunity for targeted therapeutic strategies.
Purpose of the Study:
- To develop a novel ROS-responsive nanocarrier for systemic delivery of vascular endothelial growth factor (VEGF) siRNA.
- To enhance RNAi-based cancer therapy through targeted and efficient siRNA release.
- To investigate the potential of this nanocarrier for anti-cancer applications.
Main Methods:
- Design and synthesis of a ROS-responsive boronic acid-based nanocarrier with a lipid envelope.
- Systemic administration of the nanocarrier loaded with VEGF siRNA in a tumor model.
- Evaluation of siRNA release kinetics, biodistribution, VEGF knockdown, anti-angiogenesis, and tumor growth inhibition in vivo.
Main Results:
- The developed nanocarrier demonstrated efficient systemic siRNA delivery to tumor sites.
- ROS responsiveness mediated timely siRNA release, enhancing therapeutic efficacy.
- Effective knockdown of VEGF was achieved, leading to significant anti-angiogenesis and tumor growth inhibition.
- The lipid layer shielded polyplexes, and the boronic moiety stabilized siRNA.
Conclusions:
- A new systemic siRNA delivery strategy was established by integrating a ROS-responsive boronic polymer with multifunctional lipid coatings.
- This nanocarrier system shows significant potential for advancing RNAi-based cancer therapy.
- The findings contribute to the development of precision nanomedicine for cancer treatment.
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