Kalarikkal Charutha, Bhattacharjee Sarbani, Mapa Koyeli, P Chinna Ayya Swamy
Main group Organometallics Optoelectronic Materials and Catalysis lab, Department of Chemistry, National Institute of Technology, Calicut, 673601, India.
Protein Homeostasis Laboratory, Department of Life Sciences, School of Natural Sciences, Shiv Nadar Institution of Eminence, Delhi-NCR, Greater Noida, Gautam Buddha Nagar, Uttar Pradesh 201314, India.
J Mater Chem B. 2025 Jan 22;13(4):1474-1486. doi: 10.1039/d4tb02405b.
Lipid droplets (LDs) are dynamic, multifunctional organelles critical for regulating energy balance, cell signaling, membrane formation, and trafficking. Recent studies have highlighted LDs as emerging cancer biomarkers, with cancer cells typically exhibiting a higher number and viscosity of LDs compared to normal cells. This discovery paves the way for developing molecular probes that can monitor intracellular viscosity changes within LDs, offering a powerful tool for early cancer diagnosis, recurrence monitoring, and therapeutic interventions. In this study, we designed and synthesized two series of donor-acceptor (D-A) conjugated BODIPY-cyanostilbene based fluorophores (5a-c and 6a-c) by fine-tuning the cyanostilbene unit with three distinct substituents (OMe, H, Cl) and modulating the molecular conformation rigidifying the indacene core. While the terminal substituents had a minimal effect on the optical properties, changes in molecular conformation significantly impacted the photophysical behavior of the fluorophores. Compounds 5a-c function as molecular rotors, with the free rotation of the -biphenyl rings leading to non-radiative deactivation of the excited state, resulting in weak emission. Additionally, this structural feature makes them highly responsive to changes in viscosity. As the glycerol concentration increased from 0% to 99%, the fluorescence intensity of compounds 5a, 5b, and 5c increased dramatically by 17-fold, 78-fold, and 43-fold, respectively. In contrast, compounds 6a-c, with restricted phenyl ring rotation due to tetra-methyls on the indacene unit, showed only a modest 2-3-fold increment in fluorescence intensity under similar conditions. These fluorophores possess several key advantages, including high selectivity for LDs, good photostability, sensitivity to viscosity, and responsiveness to polarity and pH. Moreover, they effectively differentiate between normal and cancer cells, making them valuable tools for cancer diagnosis and potential therapeutic applications.
脂滴（LDs）是动态的多功能细胞器，对调节能量平衡、细胞信号传导、膜形成和运输至关重要。最近的研究强调脂滴是新兴的癌症生物标志物，与正常细胞相比，癌细胞通常表现出更高数量和更高粘度的脂滴。这一发现为开发能够监测脂滴内细胞内粘度变化的分子探针铺平了道路，为早期癌症诊断、复发监测和治疗干预提供了强大工具。在本研究中，我们通过用三种不同的取代基（甲氧基、氢、氯）微调氰基芪单元并调节分子构象使茚并核心刚性化，设计并合成了两个系列的供体-受体（D-A）共轭基于硼二吡咯-氰基芪的荧光团（5a-c和6a-c）。虽然末端取代基对光学性质影响最小，但分子构象的变化显著影响了荧光团的光物理行为。化合物5a-c用作分子转子，联苯环的自由旋转导致激发态的非辐射失活，从而导致发射较弱。此外，这一结构特征使它们对粘度变化高度敏感。随着甘油浓度从0%增加到99%，化合物5a、5b和5c的荧光强度分别急剧增加了17倍、78倍和43倍。相比之下，由于茚并单元上的四甲基导致苯环旋转受限，化合物6a-c在类似条件下荧光强度仅适度增加2-3倍。这些荧光团具有几个关键优势，包括对脂滴的高选择性、良好的光稳定性、对粘度的敏感性以及对极性和pH的响应性。此外，它们能有效区分正常细胞和癌细胞，使其成为癌症诊断和潜在治疗应用的有价值工具。
