EGFR（表皮生长因子受体）与MET（肝细胞生长因子受体）之间的相互作用在分子信号传导领域中带来了重大挑战。它们的复杂相互作用导致失调并促进了癌症进展和治疗抵抗力。β-谷甾醇（BS）是一种植物甾醇，具有抗癌的潜力，其研究在作为化学预防剂的可能性上有了增加。然而，由于其较低的效力，需要进行重要的改进以在癌细胞中传递BS。本研究旨在设计一种基于载体介导的递送系统，专门针对EGFR和MET受体相互作用的癌细胞。对BS进行了表面修饰，使用了超顺磁性氧化铁纳米颗粒（SPIONs）、聚乙二醇（PEG）和聚N-异丙基丙烯酰胺（PNIPAM），以增强BS在目标位点的递送。分别将BS与SPIONs（BS-S）、PNIPAM（BS-SP）、PEG和PNIPAM（BS-SPP）聚合物进行了连接，并对连接复合物进行了表征。结果显示，BS-S、BS-SP和BS-SPP的尺寸、稳定性和单分散性依次增加。药物封装效率在BS-SPP（82.5%）、BS-S（61%）和BS-SP（74.9%）中观察到最高值。BS-SP（82.6%）和BS-SPP（83%）都实现了持续药物释放。BS、BS-S、BS-SP和BS-SPP对MCF 7的IC50值分别为242 µg/mL、197 µg/mL、168 µg/mL和149 µg/mL，对HEPG2的IC50值分别为274 µg/mL、261 µg/mL、233 µg/mL和207 µg/mL，对NCIH 460的IC50值分别为191 µg/mL、185 µg/mL、175 µg/mL和164 µg/mL，表明对NCIH 460细胞具有最高的抑制作用。我们的结果表明，β-谷甾醇与SPION、PEG和PNIPAM结合可能是一种潜在的靶向疗法，可抑制EGFR和MET受体表达的癌细胞。

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.