Titanate nanotubes: towards a novel and safer nanovector for cardiomyocytes*

Abstract

Actively contractile cardiomyocyte (CM) monolayer represents an interesting tool to study both cardiac diseases and injuries. However, this model is poorly transfectable with conventional agents. Consequently, there is a need to develop new carriers that could overcome this problem. Titanate nanotubes (TiONts) could be a potential candidate due to possibly higher cell uptake as a direct consequence of their shape. On the basis of this rationale, TiONts were assessed for their cytotoxicity and internalization pathways. Cytotoxicity was assessed for TiONts either functionalized with PEI or unfunctionalized and its spherical counterpart P25 TiO2. No cytotoxic effect was observed under TiONts, TiONts-PEI1800 and P25 TiO2 exposed conditions. The tubular morphology was found to be an important parameter promoting internalization while reversing the charge was assessed as non-additional. Internalization was found to occur by endocytosis and diffusion through the membrane. A preliminary transfection study indicated the potential of TiONts as a nanocarrier.

Toxicological Risk Assessment of Emerging Nanomaterials: Cytotoxicity, Cellular Uptake, Effects on Biogenesis and Cell Organelle Activity, Acute Toxicity and Biodistribution of Oxide Nanoparticles

“…Interestingly, the degree of ion exchange via acid treatment, which partly or entirely substitutes sodium cations by hydrogen cations, is a key parameter that drives the cytotoxicity of titanate nanowires [30]. Titanate nanotubes that were not treated with acid did not induce significant cytotoxic effect in cardiomyocytes, as seen by MTT assay performed between 1 and 10 μg/mL TiONts [31]. Similarly, TiONts concentration ranging up to 100 μg/mL do not induce detectable cytotoxicity in glioblastoma cell lines [32].…”

“…Indeed, due to their needle-like morphology, bare TiONts are internalized in cells not only by endocytosis, but also by diffusion across the plasma membrane, as observed by TEM analysis for cardiomyocytes [31], SNB19 and U87-MG glioblastoma cell lines [32]. Nanotubes display a significant higher specific surface compared to their spherical counterparts [2] and this potentially modifies their degree of interaction with plasma proteins and cells.…”

“…Nanotubes display a significant higher specific surface compared to their spherical counterparts [2] and this potentially modifies their degree of interaction with plasma proteins and cells. Our group has observed that even by incubating 4 times more spherical TiO 2 than TiONts with cardiomyocyte cells to account for the difference in specific surface values, TiONts were internalized in much more cells than spherical TiO 2 [31]. Cell penetration via diffusion, along with their increased specific area, potentially makes them an excellent candidate as a new nanomedicine platform after careful assessment of their cytotoxicity in each targeted cell model.…”

“…The cytotoxicity of titanate nanotubes made by hydrothermal treatment has been assessed in H596 human lung tumor cells [30], cardiomyocytes [31], SNB19 and U87-MG glioblastomas [32], Caco-2 cells [33], as well as 22Rv1 prostate cancer cells [8]. Interestingly, the degree of ion exchange via acid treatment, which partly or entirely substitutes sodium cations by hydrogen cations, is a key parameter that drives the cytotoxicity of titanate nanowires [30].…”

“…For instance, we have observed that ZnO nanoparticles induce a loss of lysosome membrane integrity in BV2 cells at high-dose exposure (80 mg/mL) as seen by flow cytometry detection of acridine orange (Figure 2). Additionally, double-membrane vesicles closely resembling autophagosomes have been observed by TEM, following 6 h of cardiomyocyte incubation with TiONts [31]. As the lysosomal pathway may have beneficial or detrimental effects on cell activity, a panel of assays is required to define the influence of nanoparticles on this organelle and its potential consequences in major diseases (metabolic diseases, cancer and neurodegenerative diseases).…”