Upconverting Nanorockers for Intracellular Viscosity Measurements During Chemotherapy

Abstract

molecules and organelles inside the cell. It is also a reliable indicator of the cellular state, which can be used to detect the appearance and onset of different diseases, including cancer. [1] The precise knowledge of the intracellular viscosity can be used to evaluate the effects caused by different treatments at the single-cell level. Indeed, cytoplasmic viscosity is modified when cancer cells are subjected to a chemotherapy process, so that variations in the intracellular viscosity can be used to assess the evolution of the treatment. [2] The intracellular environment is a composite of water and a variety of proteins and organelles. One of the main protein components of the cytoplasm is the cytoskeleton. This 3D network composed of filamentous proteins is a highly mobile, viscoelastic, and flexible entity that controls the cellular mechanics. [3] Particularly, alterations produced in the intracellular viscosity due to drug administration are governed by the effect of the chemical on the cytoskeleton of the cell. There are three major types of cytoskeletal filaments: microtubules, actin filaments, and intermediate filaments. They differ from each other in their molecular structure, function, and mechanical properties. These filamentous proteins, and other associated proteins, have Chemicals capable of producing structural and chemical changes on cells are used to treat diseases (e.g., cancer). Further development and optimization of chemotherapies require thorough knowledge of the effect of the chemical on the cellular structure and dynamics. This involves studying, in a noninvasive way, the properties of individual cells after drug administration. Intracellular viscosity is affected by chemical treatments and it can be reliably used to monitor chemotherapies at the cellular level. Here, cancer cell monitoring during chemotherapeutic treatments is demonstrated using intracellular allocated upconverting nanorockers. A simple analysis of the polarized visible emission of a single particle provides a real-time readout of its rocking dynamics that are directly correlated to the cytoplasmic viscosity. Numerical simulations and immunodetection are used to correlate the measured intracellular viscosity alterations to the changes produced in the cytoskeleton of cancer cells by anticancer drugs (colchicine and Taxol). This study evidences the possibility of monitoring cellular properties under an external chemical stimulus for the study and development of new treatments. Moreover, it provides the biomedical community with new tools to study intracellular dynamics and cell functioning.

Initiating revolutions for optical manipulation: the origins and applications of rotational dynamics of trapped particles

“…The particle undergoes libration, which is a harmonic motion about the polarisation axis with a spring constant κ θ which linearly increases with the trapping power. Alignment and librational motion have been demonstrated in over-and under-damped conditions for a wide range of particles such as fluorinated polyimide microparticles [80], wax microdisks [70] (Figure 2(d)), nanodumbbells [81], anisotropic diamond crystals [75], nanofabricated silicon cylinders [82], YLF crystals [83], and non-spherical birefringent NaYF 4 particles [18].…”

“…The control over the alignment of the particle can be used to enhance the light-particle interaction, e.g. to increase the percentage of laser power absorbed by the particle [83] (Section 5.4), while the librational motion can be used to study properties of the environment such as viscosity [18] (Section 5.3) and the temperature of the particle itself [83] (Section 5.4).…”

“…This motivated the search for novel optically anisotropic materials such as liquid-crystal emulsions [47,148,149] (Figure 5(c)), polymers [70,80] or birefringent synthetic crystals. Micro and nanoparticles made of fluoride crystals, such as LiYF 4 (YLF) [83,150] and NaYF 4 [17,18,61,151,152] (Figure 5(d)), have also been aligned and spun in optical traps. The main feature of these particles is that the synthesis procedure allows them to be doped with rare-earth ions that provide them with special characteristics such as the ability to control [83,150] and measure [152] temperature.…”

“…The rotation of the particle can also be monitored via the rotational Doppler effect [179]. Finally, the spectral shape of the emission of certain types of luminescent particles is orientation-dependent and can therefore also be used to track the rotational motion [18,61].…”

“…Optical manipulation inside living cells [13] and even living animals [14,15] has been proven. Either endogenous or exogenous (whether inserted [16] or internalised [17,18]) material can be manipulated, which enables the in situ study of biological processes. Separately, optical tweezers in liquid environments has given major insights into several physical phenomena including thermodynamics.…”