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Updated: Jul 12, 2025
Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids
Published on: November 22, 2021
Development of light and pH-dual responsive self-quenching theranostic SPION to make EGFR overexpressing micro tumors
Nihan Verimli1, S İrem Goralı1, Beyza Abisoglu2
1Research Institute for Health Science and Technologies (SABITA), 34810 Istanbul, Turkey; International School of Medicine, Medical Biochemistry, Istanbul Medipol University, 34810 Istanbul, Turkey.
Abstract:
Drug resistant and undetectable tumors easily escape treatment leading metastases and/or recurrence of the lethal disease. Therefore, it is vital to diagnose and destroy micro tumors using simple yet novel approaches. Here, we present fluorescence-based detection and light-based destruction of cancer cells that are known to be resistant to standard therapies. We developed a superparamagnetic iron oxide nanoparticle (SPION)-based theranostic agent that is composed of self-quenching light activated photosensitizer (BPD) and EGFR targeting ligand (Anti-EGFR ScFv or GE11 peptide). Photosensitizer (BPD) was immobilized to PEG-PEI modified SPION with acid-labile linker. Prior to stimulation of the theranostic system by light its accumulation within cancer cells is vital since BPD phototoxicity and fluorescence is activated by lysosomal proteolysis. As BPD is cleaved, the system switches from off to on position which triggers imaging and therapy. Targeting, therapeutic and diagnostic features of the theranostic system were evaluated in high and moderate level EGFR expressing pancreatic cancer cell lines. Our results indicate that the system distinguishes high and moderate EGFR expression levels and yields up to 4.3-fold increase in intracellular fluorescence intensity. Amplification of fluorescence signal was as low as 1.3-fold in the moderate or no EGFR expressing cell lines. Anti-EGFR ScFv targeted SPION caused nearly 2-fold higher cell death via apoptosis in high EGFR expressing Panc-1 cell line. The developed system, possessing advanced targeting, enhanced imaging and effective therapeutic features, is a promising candidate for multi-mode detection and destruction of residual drug-resistant cancer cells.
Insights
A novel superparamagnetic iron oxide nanoparticle (SPION) theranostic agent targets and destroys drug-resistant cancer cells. This system enhances fluorescence imaging and light-activated therapy for improved detection and treatment of residual tumors.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Drug-resistant tumors pose significant challenges, leading to metastasis and recurrence.
- Early diagnosis and destruction of micro-tumors are crucial for effective cancer treatment.
- Novel theranostic approaches are needed to overcome limitations of standard therapies.
Purpose of the Study:
- To develop and evaluate a superparamagnetic iron oxide nanoparticle (SPION)-based theranostic agent for fluorescence-based detection and light-activated destruction of drug-resistant cancer cells.
- To assess the targeting, imaging, and therapeutic capabilities of the developed theranostic system in pancreatic cancer cell lines with varying EGFR expression levels.
Main Methods:
- Development of a theranostic agent comprising SPIONs, a self-quenching photosensitizer (BPD), and an EGFR-targeting ligand (Anti-EGFR ScFv or GE11 peptide).
- Immobilization of BPD to PEG-PEI modified SPIONs using an acid-labile linker for light-activated phototoxicity and fluorescence.
- Evaluation of the theranostic system's targeting, fluorescence enhancement, and cell-killing efficacy in high and moderate EGFR-expressing pancreatic cancer cell lines.
Main Results:
- The theranostic system effectively distinguished between high and moderate EGFR expression levels, yielding up to a 4.3-fold increase in intracellular fluorescence intensity.
- A lower fluorescence signal amplification (1.3-fold) was observed in cell lines with moderate or no EGFR expression.
- Anti-EGFR ScFv targeted SPIONs induced a nearly 2-fold increase in apoptosis in high EGFR-expressing Panc-1 cells.
Conclusions:
- The developed SPION-based theranostic agent demonstrates advanced targeting, enhanced imaging, and effective therapeutic features.
- This system shows promise for multi-mode detection and destruction of residual drug-resistant cancer cells.
- The theranostic approach offers a novel strategy to combat challenging, therapy-resistant malignancies.
