Morphological Dynamics of Leukemia Cells on TiO2 Nanoparticle Coatings Studied by AFM

Jaime Andres Garcia Diosa,Ruben Jesus Camargo Amado,Adrian Keller,Guido Grundmeier,Alejandro Gonzalez Orive

doi:10.3390/app11219898

Jaime Andres Garcia Diosa, Ruben Jesus Camargo Amado + Show 3 more

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https://doi.org/10.3390/app11219898

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Abstract

Coatings of modified TiO2 nanoparticles (TiO2-m) have been shown to effectively and selectively trap non-adherent cancer cells, with an enormous potential for applications in photodynamic therapy (PDT). Leukemia cells have a remarkable affinity for TiO2-m coatings, adhering to the surface by membrane structures and exhibiting morphologic characteristics of amoeboid locomotion. However, the details of the cell–substrate interaction induced by the TiO2-m coating remain elusive. With the aim to obtain a better understanding of this phenomenon, leukemia cell adhesion to such coatings was characterized by atomic force microscopy (AFM) for short contact times up to 60 min. The cell and membrane morphological parameters mean cell height, contact area, cell volume, and membrane roughness were determined at different contact times. These results reveal cell expansion and contraction phases occurring during the initial stage of adhesion. Subsequently, the leukemic cells reach what appears to be a new resting state, characterized by pinning of the cell membrane by TiO2-m nanoparticle aggregates protruding from the coating surface.

Highlights

Photodynamic therapy (PDT) is an approach to treating infections and cancer by exploiting the production of reactive oxygen species (ROS) by illumination of an administered photosensitizer (PS)
TiO2 nanoparticles have already been employed in the PDT treatment of different types of adherent cancer cells such as prostate, cervical, breast, and colon cancer, among others [6,7,8,9]
We found that leukemia cell adhesion to TiO2 -m nanoparticle coatings starts with rapid movements of expansion and contraction, after which the cells seem to enter an immobile state with their cell membranes being pinned by TiO2 -m nanoparticle aggregates protruding from the coating surface

Summary

Introduction

Photodynamic therapy (PDT) is an approach to treating infections and cancer by exploiting the production of reactive oxygen species (ROS) by illumination of an administered photosensitizer (PS). PSs such as KillerRed [4], as well as various nanomaterials With regard to the latter, TiO2 nanoparticles have attracted particular attention because they present numerous advantages over other established PSs, such as low production cost and straightforward synthesis, chemical stability, biological inertness, and high light conversion efficiency [5,6]. It is rather challenging to treat advanced disseminated disease or non-adherent cancers such as leukemia with PDT. This is because the PS would have to freely travel through the patient’s bloodstream and require whole body irradiation, which is often impractical and sometimes even impossible [11,12]. There are only a few published in vivo or ex vivo studies on the PDT treatment of leukemia [13]

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