Nanomaterials for cell actuation at low light intensities of NIR light

Abstract

Electrical stimulation of tissues has a wide range of biomedical applications. However, current wired electro-stimulators are bulky and invasive. Wireless cell stimulation with opto-electric devices can be an alternative to generate local actuation with minimal invasiveness. However, most opto-electronic devices for cell electro-stimulation use visible light, limiting the applications to superficial tissues. Therefore, new wireless opto-electronics devices optimized to work under low intensity near infrared (NIR) light within the first or second biological spectral windows, in which light penetration in tissues is maximized, are highly demanded. NIR light is also used in cancer photodynamic therapies. However, typical photodynamic molecules have low efficiency in the NIR and poor stability. To solve this problem, novel nanomaterials are currently being explored to generate therapeutic reactive oxygen species with NIR light. In this line, the narrow bandgap, outstanding photocatalytic activity, and biocompatibility of MoS2 nanostructures position them as promising photodynamic agents. Within this framework, we have focused on the development of different opto-electronic devices for wireless cell stimulation and photodynamic therapy operated with low-intensity, safe, and high penetration NIR light. The first opto-electronic device was based on Si/Au nanowires with an in-built pn junction. Short and long nanowire arrays were fabricated through a cost-effective/scalable colloidal lithography technique. The short-Si/Au nanowires device, featuring a protected pn junction buried in the silicon structure, showed a very good opto-electrical performance under 810 nm illumination (first biological window). The Si/Au nanowires enhanced light absorption through hybrid plasmonic metal/dielectric resonances. These devices exhibited similar photovoltages, but much higher photocurrents compared to the standard flat Si pn junction, thus enabling cell stimulation through combined capacitive/faradaic processes. Si/Au nanowires exhibited high biocompatibility for osteoblast cells. Under very low intensity of 810 nm light (4. 5 µW/mm2), cells demonstrated enhanced proliferation over 21 days compared to dark conditions. Photo-induced signals triggered calcium influxes through activation of voltage-gated Ca2+ channels, even at 1 µW/mm2. Differentiation studies revealed increased alkaline phosphatase levels and calcium deposit formation under light actuation compared to dark conditions. Although, short-Si/Au nanowires produced lower photovoltages and photocurrents in the second biological window (1050 nm), they are promising for future experiments. In contrast, long-Si/Au nanowires with exposed pn junction to the electrolyte experienced a large drop in photovoltage/photocurrent. Protection strategies of the pn junction improved opto-electrical signals, showing potential for future studies. Long-Si/Au nanowires easily released from the silicon support to a liquid phase, which can be exploited for direct nanowire injection inside tissues or to develop soft implantable devices with minimal invasiveness. The second opto-electronic device was based on Si/Pt nanoneedle arrays, featuring Schottky junctions for cell stimulation within the second biological window. They exhibited good photo-electrical response although optimization is required for enhanced performance. Similar response was obtained by activation from the nanoneedles or flat silicon sides due to the high transparency of Si, being advantageous for biomedical applications. Osteoblast cells grew well attached on the nanoneedle surface. Although only 17% of the cells were activated upon illumination (3. 4-fold increase compared to dark condition), the biocompatibility and potential improvement capacity of the Si/Pt nanoneedle devices make them promising for further studies. Finally, SiO2/MoS2/Cu2O nanoreactors were explored as photodynamic platform in the first biological window for cancer therapy. The immobilized and dispersed nanoreactors demonstrated biocompatibility. Upon low intensity NIR illumination (660/808nm) a remarkable decrease in the viability of bone tumoral cells was observed due to the photogenerated reactive oxygen species. An apoptotic mechanism of cell death was detected. Internalization of the dispersed nanoreactors was low, requiring further optimization. This work offers promising avenues for advanced NIR photodynamic agents.

Date of Award	25 Apr 2024
Original language	English
Supervisor	Maria del Carme Nogues Sanmiquel (Director), Borja Sepúlveda Martínez (Director) & Maria Jose Esplandiu Egido (Director)