In vitrointeraction and biocompatibility of titanate nanotubes with microglial cells

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Abstract

Titanate nanotubes (TiONts) are promising agents for biomedical applications. Microglial activation and associated oxidative burst are major challenges in drug delivery applications across the brain. Here, TiONts were designed for drug delivery systems by functionalizing them with (3-aminopropyl) triethoxysilane (APTES), their interactions and biocompatibility were studied in vitro using murine microglial BV-2 cells. TiONts-APTES exposure resulted in increased ROS production and transient mitochondrial hyperpolarization. However, there was no indication of microglial proliferation in BV-2 cells as suggested by cell cycle analysis and morphology evaluation. The endocytosis as well as passive diffusion mediated TiONts-APTES internalization were proved by transmission electron microscopy (TEM) with and without amiloride, an endocytosis inhibiting agent. In addition, the TiONts-APTES exhibited good biocompatibility on microglial BV-2 cells as revealed by the plasma membrane integrity, lysosmal membrane integrity, morphology and viability analysis.

Graphical abstract

(3-aminopropyl) triethoxysilane (APTES) functionalized titanate nanotubes (named TiONts on the scheme) enter the BV-2 cell both via endocytosis and passive diffusion. Inside cell, TiONts-APTES are capable of inducing superoxide radicals which later get converted to peroxides by SOD activity. TiONts-APTES interact with mitochondria to induce a transient increase in ΔΨm which further gives way to mitochondria mediated ROS production. TiONts-APTES do not affect lysosomal integrity or cell cycle pattern. At high concentration TiONts-APTES probably induce caspase-mediated apoptosis in BV-2 cells leading to PARP cleavage.

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