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Cellular programming of naïve T cells can improve the efficacy of adoptive T-cell therapy. However, the current ex vivo engineering of T cells requires the pre-activation of T cells, which causes them to lose their naïve state. In this study, cationic-polymer-functionalized nanowires were used to pre-program the fate of primary naïve CD8+T cells to achieve a therapeutic response in vivo. This was done by delivering single or multiple microRNAs to primary naïve mouse and human CD8+T cells without pre-activation. The use of nanowires further allowed for the delivery of large, whole lentiviral particles with potential for long-term integration. The combination of deletion and overexpression of miR-29 and miR-130 impacted the ex vivo T-cell differentiation fate from the naïve state. The programming of CD8+T cells using nanowire-delivered co-delivery of microRNAs resulted in the modulation of T-cell fitness by altering the T-cell proliferation, phenotypic and transcriptional regulation, and secretion of effector molecules. Moreover, the in vivo adoptive transfer of murine CD8+T cells programmed through the nanowire-mediated dual delivery of microRNAs provided enhanced immune protection against different types of intracellular pathogen (influenza and Listeria monocytogenes). In vivo analyses demonstrated that the simultaneous alteration of miR-29 and miR-130 levels in naïve CD8+T cells reduces the persistence of canonical memory T cells whereas increases the population of short-lived effector T cells. Nanowires could potentially be used to modulate CD8+T-cell differentiation and achieve a therapeutic response in vivo without the need for pre-activation.

Wearable pressure sensors with wide operating pressure ranges and enhanced wearability via seamless integration with circuits can greatly improve the fields of digital healthcare, prosthetic limbs, and human–machine interfaces. Herein, we report an approach based on a conductive-island-bridging nanonetwork to realize wearable resistive pressure sensors that are operative over ultrawide pressure ranges >400 kPa and are circuit-compatible. The sensor has a simple two-layered structure, where nanonetworks of single-walled carbon nanotubes selectively patterned on a surface-modified elastomeric film interface and bridge conductive Au island patterns on printed circuit boards (PCBs). We show that varying the design of the Au islands and the conductivity of the nanonetworks systematically tunes the sensitivity, linearity, and the operation range of the pressure sensor. In addition, introducing microstructured lead contacts into the sensor based on a Au-island-bridging nanonetwork produces a record-high sensitivity of 0.06 kPa–1at 400 kPa. Furthermore, the PCB that serves as the bottom layer of the pressure sensor and contains embedded interconnects enables facile integration of the sensor with measurement circuits and wireless communication modules. The developed sensor enables the monitoring of wrist pulse waves. Moreover, an insole-shaped PCB-based pressure-sensing system wirelessly monitors pressure distributions and gait kinetics during walking. Our scheme can be extended to other nanomaterials and flexible PCBs and thus provides a simple yet powerful platform for emerging wearable applications.

Flexible piezoresistive sensors have huge potential for health monitoring, human–machine interfaces, prosthetic limbs, and intelligent robotics. A variety of nanomaterials and structural schemes have been proposed for realizing ultrasensitive flexible piezoresistive sensors. However, despite the success of recent efforts, high sensitivity within narrower pressure ranges and/or the challenging adhesion and stability issues still potentially limit their broad applications. Herein, we introduce a biomaterial-based scheme for the development of flexible pressure sensors that are ultrasensitive (resistance change by 5 orders) over a broad pressure range of 0.1–100 kPa, promptly responsive (20 ms), and yet highly stable. We show that employing biomaterial-incorporated conductive networks of single-walled carbon nanotubes as interfacial layers of contact-based resistive pressure sensors significantly enhances piezoresistive response via effective modulation of the interlayer resistance and provides stable interfaces for the pressure sensors. The developed flexible sensor is capable of real-time monitoring of wrist pulse waves under external medium pressure levels and providing pressure profiles applied by a thumb and a forefinger during object manipulation at a low voltage (1 V) and power consumption (<12 μW). This work provides a new insight into the material candidates and approaches for the development of wearable health-monitoring and human–machine interfaces.