Related Experiment Video
Updated: Mar 2, 2026
Author Spotlight: Innovative Cancer Therapies with Iron Oxide Nanoparticles for Glioblastoma Treatment
Published on: September 27, 2024
Lipoprotein-biomimetic nanostructure enables efficient targeting delivery of siRNA to Ras-activated glioblastoma
Jia-Lin Huang1, Gan Jiang1, Qing-Xiang Song1
1Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China.
Abstract:
Hyperactivated Ras regulates many oncogenic pathways in several malignant human cancers including glioblastoma and it is an attractive target for cancer therapies. Ras activation in cancer cells drives protein internalization via macropinocytosis as a key nutrient-gaining process. By utilizing this unique endocytosis pathway, here we create a biologically inspired nanostructure that can induce cancer cells to 'drink drugs' for targeting activating transcription factor-5 (ATF5), an overexpressed anti-apoptotic transcription factor in glioblastoma. Apolipoprotein E3-reconstituted high-density lipoprotein is used to encapsulate the siRNA-loaded calcium phosphate core and facilitate it to penetrate the blood-brain barrier, thus targeting the glioblastoma cells in a macropinocytosis-dependent manner. The nanostructure carrying ATF5 siRNA exerts remarkable RNA-interfering efficiency, increases glioblastoma cell apoptosis and inhibits tumour cell growth both in vitro and in xenograft tumour models. This strategy of targeting the macropinocytosis caused by Ras activation provides a nanoparticle-based approach for precision therapy in glioblastoma and other Ras-activated cancers.
Insights
Researchers developed a novel nanostructure that targets Ras-activated glioblastoma cells by inducing them to internalize drugs. This nanoparticle therapy enhances cancer cell apoptosis and inhibits tumor growth, offering a new precision medicine approach.
Area of Science:
- Oncology
- Nanotechnology
- Molecular Biology
Background:
- Hyperactivated Ras signaling drives oncogenesis in cancers like glioblastoma.
- Ras activation promotes macropinocytosis, a nutrient uptake pathway in cancer cells.
- Activating transcription factor-5 (ATF5) is an anti-apoptotic factor overexpressed in glioblastoma.
Purpose of the Study:
- To develop a nanoparticle-based drug delivery system targeting Ras-activated glioblastoma.
- To leverage macropinocytosis for targeted cancer therapy.
- To inhibit ATF5 expression in glioblastoma cells.
Main Methods:
- Engineered a nanostructure using apolipoprotein E3-reconstituted high-density lipoprotein encapsulating siRNA-loaded calcium phosphate.
- Utilized the nanostructure to target glioblastoma cells via macropinocytosis-dependent endocytosis.
- Administered the nanostructure to inhibit ATF5 and assess therapeutic efficacy in vitro and in vivo.
Main Results:
- The nanostructure demonstrated efficient blood-brain barrier penetration and targeted glioblastoma cells.
- The ATF5 siRNA-loaded nanostructure achieved high RNA-interfering efficiency.
- Significant induction of glioblastoma cell apoptosis and inhibition of tumor growth were observed.
Conclusions:
- Targeting Ras-induced macropinocytosis offers a novel strategy for glioblastoma therapy.
- The developed nanostructure provides a nanoparticle-based approach for precision treatment of glioblastoma.
- This strategy holds potential for treating other Ras-activated cancers.
More Related Videos
10:33Delivery of Therapeutic siRNA to the CNS Using Cationic and Anionic Liposomes
Published on: July 23, 2016
15:55Long-term Silencing of Intersectin-1s in Mouse Lungs by Repeated Delivery of a Specific siRNA via Cationic Liposomes. Evaluation of Knockdown Effects by Electron Microscopy
Published on: June 21, 2013
