Targeted Delivery of Rapamycin via Epidermal Growth Factor Receptors in Pancreatic Cancer Cells Inhibits Cell...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Pancreatic cancer (PC) is highly aggressive with poor prognosis.
• Overexpression of epidermal growth factor receptor (EGFR) in most PC cells presents a therapeutic target.
• Rapamycin (Rap) is an mTOR inhibitor with anti-proliferative and pro-apoptotic effects.

Purpose of the Study:

• To develop and evaluate EGFR-targeted gold nanoparticles (AuNPs) for delivering rapamycin (Rap) to pancreatic cancer cells.
• To investigate the efficacy of GE11-conjugated AuNPs loaded with Rap in inhibiting PC cell proliferation and inducing apoptosis.

Main Methods:

• Conjugation of EGFR-targeting peptide (GE11) to gold nanoparticles (AuNPs).
• Loading of rapamycin (Rap) onto GE11-AuNPs and assessment of drug loading efficiency and release kinetics.
• Evaluation of cellular uptake of conjugates in PANC-1 cells (a PC cell line).
• Assessment of anti-proliferative and pro-apoptotic effects of the therapeutic conjugates in vitro.

Main Results:

• Successful conjugation of GE11 peptide to AuNPs was confirmed.
• Rapamycin loading efficiency was 41.5%, with sustained release observed at lower pH.
• GE11-AuNP-Rap conjugates demonstrated enhanced cellular uptake in PANC-1 cells compared to unmodified AuNPs.
• The conjugates effectively inhibited cell proliferation and induced apoptosis, involving pathways of reactive oxygen species, mitochondrial damage, and caspase activation.

Conclusions:

• GE11-conjugated AuNPs represent a promising nanoparticle-based strategy for targeted pancreatic cancer therapy.
• This approach enhances the delivery and efficacy of rapamycin, potentially minimizing off-target toxicity.
• The GE11-EGFR interaction facilitates targeted delivery, offering a novel therapeutic avenue for pancreatic cancer treatment.