Abstract
T cell activation is vital for immune response initiation and modulation. Except for the strength of the interaction between T cell receptors (TCR) and peptides on major histocompatibility complex molecules (MHC), mechanical force, mediated by professional mechanosensitive ion channels, contributes to activating T cells. The intrinsic characteristic of synthetic micro/nanomotors that convert diverse energy sources into physical movement and force, opening up new possibilities for T cell regulation. In this work, Pd/Au nanomotors with spiky morphology were fabricated, and in the presence of low concentrations of hydrogen peroxide fuel, the motors exhibited continuous locomotion in the cellular biological environment. Physical cues (force and pressure) generated by the dynamic performance are sensed by mechanosensitive ion channels of T cells and trigger Ca2+ influx and subsequent activation. The successful demonstration that mechanical signals generated in the bio microenvironment can potentiate T cells activation, represents a potential approach for cell-based cancer immunotherapy.
Highlights
A micro/nanomotor is a biomimetic system of natural molecular motors and micro-organisms that converts energy into movement and force (Abdelmohsen et al, 2014)
The Pd nanoparticles with special morphology were obtained by removing the oleic acid (OA)/OAm templates with ethanol washing
These results demonstrate the successful preparation of spiky-like nanomotors, indicating its geometrical asymmetry ensures an asymmetrical generation of forces
Summary
A micro/nanomotor is a biomimetic system of natural molecular motors and micro-organisms that converts energy into movement and force (Abdelmohsen et al, 2014). To propel in biological media, these artificial machines rely on either chemically powered [including hydrogen peroxide (Wilson et al, 2013), glucose (Ma et al, 2015), urea (Hortelão et al, 2018), etc.] or external energy sources [such as light (Ibele et al, 2009), ultrasonic (Lu et al, 2019) or magnetic fields (Liu et al, 2020), etc.] Such unbound tiny machines have inherent advantages such as active transport, high tissue penetration, and motion controllability, indicating immense potentials for a variety of biomedical applications in targeted drug/cell delivery (Tu et al, 2017a; Tu et al, 2017b) minimally invasive surgery (Malachowski et al, 2014; He et al, 2016) and biosensing (Molinero-Fernandez et al, 2020), etc., serving as a revolutionary toolbox for cancer diagnosis and therapy. Benefiting from the signal transduction of the immune cascade, methods have been developed to activate T cells with various cytokines (IL-6, IFN-γ, CXCL10, etc.) While effective treatment, it faces the risk of causing excessive activation of T cells and eventually leading to a cytokine storm.
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