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Synthesis of Immunotargeted Magneto-plasmonic Nanoclusters
Published on: August 22, 2014
ROS-mediated anticancer effects of EGFR-targeted nanoceria
Kochurani K Johnson1,2, Pramod Koshy1, Chantal Kopecky3
1School of Materials Science and Engineering, Faculty of Science, UNSW Sydney, Sydney, New South Wales, Australia.
Abstract:
The therapeutic effectiveness of anticancer drugs, including nanomedicines, can be enhanced with active receptor-targeting strategies. Epidermal growth factor receptor (EGFR) is an important cancer biomarker, constitutively expressed in sarcoma patients of different histological types. The present work reports materials and in vitro biomedical analyses of silanized (passive delivery) and/or EGF-functionalized (active delivery) ceria nanorods exhibiting highly defective catalytically active surfaces. The EGFR-targeting efficiency of nanoceria was confirmed by receptor-binding studies. Increased cytotoxicity and reactive oxygen species (ROS) production were observed for EGF-functionalized nanoceria owing to enhanced cellular uptake by HT-1080 fibrosarcoma cells. The uptake was confirmed by TEM and confocal microscopy. Silanized nanoceria demonstrated negligible/minimal cytotoxicity toward healthy MRC-5 cells at 24 and 48 h, whereas this was significant at 72 h owing to a nanoceria accumulation effect. In contrast, considerable cytotoxicity toward the cancer cells was exhibited at all three times points. The ROS generation and associated cytotoxicity were moderated by the equilibrium between catalysis by ceria, generation of cell debris, and blockage of active sites. EGFR-targeting is shown to enhance the uptake levels of nanoceria by cancer cells, subsequently enhancing the overall anticancer activity and therapeutic performance of ceria.
Insights
Active targeting of Epidermal Growth Factor Receptor (EGFR) with EGF-functionalized ceria nanorods enhances anticancer drug delivery and effectiveness against sarcoma cells. This strategy improves cellular uptake and therapeutic performance.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Anticancer drug efficacy can be improved using active receptor-targeting strategies.
- Epidermal Growth Factor Receptor (EGFR) is a key biomarker in various sarcoma types.
Purpose of the Study:
- To investigate the in vitro biomedical properties of silanized and EGF-functionalized ceria nanorods.
- To evaluate the EGFR-targeting efficiency and therapeutic effectiveness of these nanorods in sarcoma treatment.
Main Methods:
- Synthesis and characterization of silanized and EGF-functionalized ceria nanorods.
- In vitro receptor-binding studies to confirm EGFR-targeting.
- Assessment of cellular uptake, reactive oxygen species (ROS) production, and cytotoxicity in HT-1080 fibrosarcoma and MRC-5 cells.
- Microscopy techniques (TEM, confocal) for uptake confirmation.
Main Results:
- EGF-functionalized nanoceria demonstrated enhanced cellular uptake by HT-1080 fibrosarcoma cells via EGFR targeting.
- Increased cytotoxicity and ROS production were observed for EGF-functionalized nanoceria compared to silanized versions.
- Silanized nanoceria showed minimal cytotoxicity to healthy cells initially, but significant accumulation-induced toxicity at 72 hours.
- Cancer cells exhibited considerable cytotoxicity from nanoceria at all tested time points.
Conclusions:
- EGFR-targeting significantly enhances nanoceria uptake in cancer cells, boosting therapeutic performance.
- EGF-functionalized ceria nanorods show potential as an effective anticancer nanomedicine for sarcomas.
- The balance between ceria catalysis, cell debris, and active site blockage influences ROS generation and cytotoxicity.
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