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Modulating the Effect of β-Sitosterol Conjugated with Magnetic Nanocarriers to Inhibit EGFR and Met Receptor Cross
Shanmuga Sundari Ilangovan1, Biswanath Mahanty2, Venkatesan Perumal3
1Department of Biotechnology, Bannari Amman Institute of Technology, Sathyamangalam 638401, India.
Abstract:
The cross-talk between the EGFR (Epidermal Growth Factor Receptor) and MET (Hepatocyte Growth Factor Receptor) poses a significant challenge in the field of molecular signaling. Their intricate interplay leads to dysregulation and contributes to cancer progression and therapeutic resistance. β-Sitosterol (BS), a plant sterol with promising anticancer properties, shows increased research on its potential as a chemopreventive agent. However, significant modifications are required to deliver BS in cancer cells due to its lower efficacy. The present work aims to design a carrier-mediated delivery system specifically targeting cancer cells with EGFR and MET receptor cross-talk. Surface modification of BS was performed with superparamagnetic iron oxide nanoparticles (SPIONs), polyethylene glycol (PEG), and poly(N-isopropylacrylamide) (PNIPAM) to enhance the delivery of BS at the target site. BS was conjugated with SPIONs (BS-S), PNIPAM (BS-SP), PEG, and PNIPAM (BS-SPP) polymers, respectively, and the conjugated complexes were characterized. Results showed an increase in size, stability, and monodispersity in the following order, BS-S, BS-SP, and BS-SPP. The drug encapsulation efficiency was observed to be highest in BS-SPP (82.5%), compared to BS-S (61%) and BS-SP (74.9%). Sustained drug release was achieved in both BS-SP (82.6%) and BS-SPP (83%). The IC 50 value of BS, BS-S, BS-SP, and BS-SPP towards MCF 7 was 242 µg/mL,197 µg/mL, 168 µg/mL, and 149 µg/mL, HEPG2 was 274 µg/mL, 261 µg/mL, 233 µg/mL and 207 µg/mL and NCIH 460 was 191 µg/mL, 185 µg/mL, 175 and 164 µg/mL, indicating highest inhibition towards NCIH 460 cells. Our results conclude that β-sitosterol conjugated with SPION, PEG, and PNIPAM could be a potential targeted therapy in inhibiting EGFR and MET receptor-expressing cancer cells.
Insights
This study developed a targeted drug delivery system using β-sitosterol (BS) conjugated with nanoparticles to treat cancers driven by EGFR and MET receptor cross-talk. The novel formulation enhanced BS efficacy and showed potent inhibition against cancer cells.
Area of Science:
- Biotechnology and Nanomedicine
- Molecular Oncology
- Drug Delivery Systems
Background:
- Cross-talk between Epidermal Growth Factor Receptor (EGFR) and Hepatocyte Growth Factor Receptor (MET) drives cancer progression and therapeutic resistance.
- β-Sitosterol (BS), a plant sterol, exhibits anticancer properties but requires improved delivery for enhanced efficacy.
- Targeted delivery systems are crucial for overcoming limitations in delivering therapeutic agents to cancer cells.
Purpose of the Study:
- To design and characterize a carrier-mediated delivery system for β-sitosterol (BS) targeting cancer cells with EGFR and MET receptor cross-talk.
- To enhance the delivery and efficacy of BS using surface-modified superparamagnetic iron oxide nanoparticles (SPIONs), polyethylene glycol (PEG), and poly(N-isopropylacrylamide) (PNIPAM).
Main Methods:
- Surface modification of β-sitosterol (BS) with SPIONs, PEG, and PNIPAM to create conjugated complexes (BS-S, BS-SP, BS-SPP).
- Characterization of the conjugated complexes for size, stability, and monodispersity.
- Evaluation of drug encapsulation efficiency, sustained drug release, and in vitro cytotoxicity against cancer cell lines (MCF 7, HEPG2, NCIH 460).
Main Results:
- The BS-SPP complex exhibited the highest drug encapsulation efficiency (82.5%) and demonstrated sustained drug release.
- The conjugated BS formulations (BS-S, BS-SP, BS-SPP) showed significantly lower IC50 values compared to free BS across all tested cancer cell lines.
- BS-SPP demonstrated the highest inhibition against NCIH 460 cells, indicating superior anticancer activity.
Conclusions:
- β-Sitosterol conjugated with SPION, PEG, and PNIPAM (BS-SPP) represents a promising targeted therapy for inhibiting EGFR and MET receptor-expressing cancers.
- The developed nanocarrier system effectively enhances BS delivery and anticancer efficacy.
- This approach offers a potential strategy for overcoming therapeutic resistance in specific cancer types.
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