Ilangovan Shanmuga Sundari, Mahanty Biswanath, Perumal Venkatesan, Sen Shampa
Department of Biotechnology, Bannari Amman Institute of Technology, Sathyamangalam 638401, India.
Division of Biotechnology, Karunya Institute of Technology and Sciences, Coimbatore 641114, India.
Pharmaceutics. 2023 Aug 19;15(8):2158. doi: 10.3390/pharmaceutics15082158.
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.
表皮生长因子受体（EGFR）与肝细胞生长因子受体（MET）之间的相互作用给分子信号传导领域带来了重大挑战。它们复杂的相互作用导致失调，并促进癌症进展和治疗抗性。β-谷甾醇（BS）是一种具有潜在抗癌特性的植物甾醇，其作为化学预防剂的潜力受到越来越多的研究。然而，由于其疗效较低，需要进行重大改进才能将BS递送至癌细胞。目前的工作旨在设计一种载体介导的递送系统，专门靶向具有EGFR和MET受体相互作用的癌细胞。通过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）对BS进行表面修饰，以增强BS在靶位点的递送。BS分别与SPIONs（BS-S）、PNIPAM（BS-SP）、PEG和PNIPAM（BS-SPP）聚合物共轭，并对共轭复合物进行表征。结果表明，BS-S、BS-SP和BS-SPP的尺寸、稳定性和单分散性依次增加。与BS-S（61%）和BS-SP（74.9%）相比，观察到BS-SPP的药物包封效率最高（82.5%）。BS-SP（82.6%）和BS-SPP（83%）均实现了药物的持续释放。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细胞的抑制作用最强。我们的结果表明，与SPION、PEG和PNIPAM共轭的β-谷甾醇可能是抑制表达EGFR和MET受体的癌细胞的一种潜在靶向治疗方法。
