开发新的和-药物合物,以向FGFR2受体表达瘤细胞和3D球状体
Mary A Biggs1, Amrita Das1, Beatriz G Goncalves1
1Department of Chemistry and Biochemistry, Fordham University, 441 East Fordham Road, Bronx, NY 10458, USA.
Biomimetics (Basel, Switzerland)
|September 27, 2024
概括
这项研究引入了针对FGFR2过度表达瘤细胞的新型联. 该Trimer-pep-DOX结合体显示出优异的药物输送和细胞毒性对胃癌细胞和3D瘤.
科学领域:
- 生物模拟化学是生物模拟化学.
- 分子生物学分子生物学
- 药物输送系统是药物输送系统.
背景情况:
- 纤维细胞生长因子受体2 (FGFR2) 在各种瘤细胞中过度表达,使其成为潜在的治疗点.
- 来自自然资源的简短生物活性具有针对性药物递送的潜力.
研究的目的:
- 研究新序列 (A-pep,L-pep,Trimer-pep) 与FGFR2激酶域的结合相互作用.
- 开发用于向癌症治疗的类药物联合体.
- 评估这些结合物的有效性,以向瘤细胞和3D瘤.
主要方法:
- 分子对接和动力学模拟以分析-FGFR2相互作用.
- 酸-多克索鲁比 (DOX) 结合物的合成.
- 表面等离子体共振 (SPR) 用于结合确认.
- 在KATO III胃癌细胞上的体外细胞毒性测定.
- 使用共同培养的瘤细胞和癌症相关纤维细胞 (CAFs) 的3D球形透研究.
主要成果:
- 酸ACSAG (A-pep) 和LPHVLTPEAGAT (L-pep),以及它们的融合Trimer-pep,与FGFR2激酶域结合.
- 与正常细胞相比,-DOX合物对KATO III细胞具有增强的细胞毒性.
- 三元--DOX合物显示了对3D球体的透率最高,其次是ACSAG合物.
结论:
- 开发的联体显示出针对FGFR2表达瘤的向药物递送的前景.
- 特里默-pep对开发用于胃癌和其他FGFR2驱动的恶性瘤的先进治疗方法具有显著的潜力.
- 对这些联体的进一步探索可能会导致新的癌症治疗策略.
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