Department of Chemistry, Pilani Campus, BITS, Pilani, Rajasthan 333031, India.
Dalton Trans. 2018 Mar 26;47(13):4613-4624. doi: 10.1039/c7dt04232a.
Advanced biomedical research has established that cancer is a multifactorial disorder which is highly heterogeneous in nature and responds differently to different treatment modalities, due to which constant monitoring of therapy response is becoming extremely important. To accomplish this, different theranostic formulations have been evaluated. However, most of them are found to suffer from several limitations extending from poor resolution, radiation damage, to high costs. In order to develop a better theranostic modality, we have designed and synthesized a novel platinum(ii)-based 'aggregation induced emission' (AIE) molecule (named BMPP-Pt) which showed strong intra-cellular fluorescence and also simultaneously exhibited potent cytotoxic activity. Due to this dual functionality, we wanted to explore the possibility of using this compound as a single molecule based theranostic modality. This compound was characterized using elemental analysis, NMR and IR spectroscopy, mass spectrometry and single crystal X-ray structure determination. BMPP-Pt was found to exhibit a high AIE property with emission maxima at 497 nm. For more efficient cancer cell targeting, BMPP-Pt was encapsulated into mesoporous silica nanoparticles (Pt-MSNPs) and the MSNPs were further surface modified with an anti-EpCAM aptamer (Pt-MSNP-E). Pt-MSNPs exhibited higher intracellular fluorescence compared to free BMPP-Pt, though both of them induced a similar degree of cell death via the apoptosis pathway, possibly via cell cycle arrest in the G1 phase. Anti-EpCAM aptamer modification was found to increase both cytotoxicity and intracellular fluorescence compared to unmodified MSNPs. Our study showed that EpCAM functionalized BMPP-Pt loaded MSNPs can efficiently internalize and induce apoptosis of cancer cells as well as show strong intracellular fluorescence. This study provides clues towards the development of a potential single compound based theranostic modality in future.
先进的生物医学研究已经确定,癌症是一种多因素疾病,本质上高度异质,对不同的治疗方式有不同的反应,因此对治疗反应的持续监测变得极其重要。为此,已经评估了不同的治疗诊断制剂。然而,大多数制剂都存在从较差的分辨率、辐射损伤到高成本等多种限制。为了开发更好的治疗诊断方法,我们设计并合成了一种新型的基于铂(ii)的“聚集诱导发射”(AIE)分子(命名为 BMPP-Pt),该分子表现出强烈的细胞内荧光,同时也表现出很强的细胞毒性。由于这种双重功能,我们希望探索将该化合物用作基于单分子的治疗诊断方法的可能性。该化合物通过元素分析、NMR 和 IR 光谱、质谱和单晶 X 射线结构测定进行了表征。BMPP-Pt 表现出很高的 AIE 特性,发射最大值在 497nm 处。为了更有效地靶向癌细胞,BMPP-Pt 被包封在介孔硅纳米颗粒(Pt-MSNPs)中,然后用抗 EpCAM 适体(Pt-MSNP-E)进一步表面修饰。Pt-MSNPs 表现出比游离 BMPP-Pt 更高的细胞内荧光,尽管它们都通过细胞凋亡途径诱导相似程度的细胞死亡,可能通过 G1 期细胞周期停滞。与未修饰的 MSNPs 相比,EpCAM 适体修饰增加了细胞毒性和细胞内荧光。我们的研究表明,EpCAM 功能化的 BMPP-Pt 负载的 MSNPs 可以有效地内化并诱导癌细胞凋亡,并显示出强烈的细胞内荧光。这项研究为未来开发基于单一化合物的治疗诊断方法提供了线索。