通过表皮生长因子受体在胰腺癌细胞中靶向递送雷帕霉素可抑制细胞增殖并诱导凋亡。

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

作者信息

Oluremi Adeolu S, Baldwin Christofer, Gustavison Nickolas, Bashiru Mujeebat, Oyebade Adeniyi, Siraj Noureen, Rao Raj Raghavendra, Ali Nawab

机构信息

Department of Biology, University of Arkansas at Little Rock, 2801 S. University Avenue, Little Rock, Arkansas 72004, United States.

Department of Biomedical Engineering, University of Arkansas, 1 University of Arkansas, Fayetteville, Arkansas 72701, United States.

出版信息

ACS Omega. 2025 Jul 19;10(29):31762-31775. doi: 10.1021/acsomega.5c02820. eCollection 2025 Jul 29.

Pancreatic cancer (PC) is aggressive and deadly; most PC cells overexpress an epidermal growth factor receptor (EGFR). EGFR-targeting peptide (GE11) was conjugated to gold nanoparticles (AuNPs) for delivering rapamycin (Rap), an mTOR inhibitor that reduces proliferation and induces apoptosis. Biophysical techniques confirmed the conjugation. Rap loading efficiency was 41.5%, with sustained release at a lower pH. Conjugates showed higher uptake in PANC-1 cells than unmodified AuNPs. It also inhibited proliferation and induced apoptosis via pathways involving reactive oxygen species, mitochondrial damage, and caspase activation. This approach represents a promising nanoparticle-based therapeutic strategy targeting PC cells, utilizing GE11-EGFR interactions to minimize toxicity and enhance the efficacy of the therapeutic drug.

胰腺癌（PC）具有侵袭性且致命；大多数胰腺癌细胞过度表达表皮生长因子受体（EGFR）。将靶向EGFR的肽（GE11）与金纳米颗粒（AuNP）偶联，用于递送雷帕霉素（Rap），一种可减少增殖并诱导细胞凋亡的mTOR抑制剂。生物物理技术证实了这种偶联。雷帕霉素的负载效率为41.5%，在较低pH值下具有持续释放特性。偶联物在PANC-1细胞中的摄取量高于未修饰的金纳米颗粒。它还通过涉及活性氧、线粒体损伤和半胱天冬酶激活的途径抑制增殖并诱导细胞凋亡。这种方法代表了一种有前景的基于纳米颗粒的胰腺癌治疗策略，利用GE11与EGFR的相互作用来最小化毒性并提高治疗药物的疗效。