Department of Soft Condensed Matter, Institute of Physical Chemistry PAS, 01-224 Warsaw, Poland.
Department of Medicine, Poznan University of Medical Sciences, 61-701 Poznan, Poland.
J Phys Chem Lett. 2023 Feb 9;14(5):1272-1278. doi: 10.1021/acs.jpclett.2c03590. Epub 2023 Jan 31.
Bevacizumab is a biological drug that is now extensively studied in clinics against various types of cancer. Although bevacizumab's action is preferably extracellular, there are reports suggesting its internalization into cancer cells, consequently decreasing its therapeutic potential. Here we are solving this issue by applying fluorescence correlation spectroscopy in living cells. We tracked single molecules of fluorescent bevacizumab in MDA-MB-231 and HeLa cells and proved that mobility measurements bring significant added value to standard imaging techniques. We confirmed the presence of the drug in intracellular vesicles. Additionally, we explicitly excluded the presence of a free cytosolic fraction of bevacizumab in both studied cell types. Extracellular and intracellular concentrations of the drug were measured, giving a partition coefficient on the order of 10, comparable with the spontaneous uptake of biologically inert nanoparticles. Our work presents how techniques and models developed for physics can answer biological questions.
贝伐珠单抗是一种生物药物，目前在临床上广泛研究用于治疗各种类型的癌症。尽管贝伐珠单抗的作用最好是在细胞外，但有报道表明它可以被内化到癌细胞中，从而降低其治疗潜力。在这里，我们通过在活细胞中应用荧光相关光谱来解决这个问题。我们在 MDA-MB-231 和 HeLa 细胞中跟踪了荧光贝伐珠单抗的单个分子，并证明了流动性测量为标准成像技术带来了显著的附加价值。我们证实了药物存在于细胞内囊泡中。此外，我们明确排除了在这两种研究细胞类型中存在游离胞质部分的贝伐珠单抗。测量了药物的细胞外和细胞内浓度，得到了约 10 的分配系数，与生物惰性纳米颗粒的自发摄取相当。我们的工作展示了为物理学开发的技术和模型如何回答生物学问题。
