Related Experiment Video
Updated: Jul 2, 2026
09:02
Nanoparticle Delivery of an Oligonucleotide Payload in a Glioblastoma Multiforme Animal Model
Published on: September 27, 2024
SpyCatcher-Engineered Ferritin Nanocages Enable Dual-Receptor Targeting for Enhanced Glioma Therapy
Yuan Chen1, Zhao Lou1,2, Yuteng Chu1
1Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals & College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China.
Bioconjugate Chemistry
|July 1, 2026
Summary
Engineered dual-targeted nanoparticles using ferritin (FTn) and an epidermal growth factor receptor (EGFR) affibody enhance brain tumor drug delivery. This approach improves glioblastoma treatment selectivity and efficacy while minimizing systemic toxicity.
Area of Science:
- Biotechnology
- Nanomedicine
- Oncology
Background:
- Human heavy-chain ferritin (FTn) targets transferrin receptor 1 (TfR1), showing potential for brain tumor drug delivery.
- TfR1's widespread expression in normal tissues restricts the selectivity and precision of FTn-based therapies.
- Targeting additional receptors is crucial for enhancing tumor specificity.
Purpose of the Study:
- To engineer a dual-receptor-targeting ferritin nanoplatform for improved glioblastoma drug delivery.
- To conjugate an epidermal growth factor receptor (EGFR) affibody to FTn for enhanced tumor cell targeting.
- To evaluate the efficacy and safety of the dual-targeted drug delivery system.
Main Methods:
- Developed FTn-EGFRAfb nanoparticles using the SpyCatcher/SpyTag system for site-specific conjugation.
- Encapsulated doxorubicin (DOX) into the nanoparticles (DOX@FTn-EGFRAfb) with temperature-controlled loading.
- Assessed nanoparticle uptake, cytotoxicity in vitro, and therapeutic efficacy in an orthotopic U87 glioma mouse model.
Main Results:
- The modular strategy successfully preserved FTn structure and stability, enabling precise ligand conjugation.
- DOX@FTn-EGFRAfb nanoparticles demonstrated pH-responsive drug release, high protein recovery, and stability.
- Enhanced cellular uptake and cytotoxicity were observed in TfR1/EGFR double-positive U87 glioma cells.
- Significant inhibition of tumor growth and prolonged survival were achieved in vivo with no apparent systemic toxicity.
Conclusions:
- The engineered FTn-EGFRAfb nanoplatform offers a versatile strategy for dual-targeted glioblastoma drug delivery.
- This approach enhances therapeutic precision by targeting both TfR1 and EGFR.
- The study highlights the potential of protein engineering for developing effective and safe nanomedicines for brain tumors.
