Hydrophobicity Regulation of Energy Acceptors Confined in Mesoporous Silica Enabled Reversible Activation of Optogenetics for Closed-Loop Glycemic Control

Abstract

Optogenetics-based synthetic biology holds great promise as a cell-based therapy strategy for many clinical incurable diseases; however, precise control over genetic expression strength and timing through disease state-related closed-loop regulation remains a challenge due to the lack of reversible probes to indicate real-time metabolite fluctuations. Here, based on a novel mechanism of analyte-induced hydrophobicity regulation of energy acceptors confined in mesoporous silica, we developed a smart hydrogel platform comprising glucose reversible responsive upconversion nanoprobes and optogenetic engineered cells, in which the upconverted blue light strength was adaptively tuned through blood glucose levels to control optogenetic expressions for insulin secretion. The intelligent hydrogel system enabled convenient maintenance of glycemic homeostasis through simple near-infrared illuminations without any additional glucose concentration monitoring, which efficiently avoided genetic overexpression-induced hypoglycemia. This proof-of-concept strategy efficiently combines diagnostics with optogenetics-based synthetic biology for mellitus therapy, opening up a new avenue for nano-optogenetics.

Nanothermometry for cellular temperature monitoring and disease diagnostics

“…[55][56][57][58] Lanthanide luminescent nanomaterials utilize the sensitizer and activator of lanthanide ions to absorb photon energy and convert it into luminescence. 59,60 The temperature sensitivity of lanthanide luminescent nanoparticles is shown by the thermal response distribution of excited states, energy transfer between lanthanide ions, or between lanthanide ions and phonons. 61 The temperature-dependent emission for a single type of lanthanide ion conforms to the Boltzmann statistical distribution theory.…”

“…63 Lanthanide luminescent nanomaterials are divided into down-conversion and upconversion luminescence. 60,64 There are many applications of downconversion luminescence nanoparticles in in vivo temperature detection. For example, Jacinto et al designed the co-doped Yb 3þ /Nd 3þ core/shell nanoparticles to measure subcutaneous thermal transients in small animal models to obtain fundamental properties such as absorption coefficient and thermal diffusivity of the relevant tissues.…”

Nano-optogenetics for Disease Therapies

“…Recently, our group has designed a glucose-reversible responsive nanoprobe to dynamic regulation of optogenetic activation for secreting of insulin (Figure 12b). 115 In detail, the phenylboronic acid-modified fluorescein molecule exhibits reversible hydrophobic properties before and after reaction with glucose so that it can achieve reversible inward/outward migration in the hydrophobic pores of the mesoporous silica layer, change its energy transfer efficiency with nanoparticles, and dynamically adjust the blue light intensity of UCNPs. The reversible probe was further encapsulated with optogenetically engineered cells to form an intelligent hydrogel, in which the blue fluorescence initiated a downstream cascade pathway that synthesized GLP-1, and stimulated islet cells to synthesize insulin and reduce blood glucose concentration.…”

Near-infrared light responsive intensified multiphoton ultraviolet upconversion in nanostructures towards efficient reactive oxygen species generation

“…Among multiple types of upconversion emission, high-order multiphoton UV upconversion has attracted much attention and has been applied in the frontier fields of biological detection, 10–14 drug delivery, 6,15,16 optogenetics and photochemistry. 17,18…”

“…Among multiple types of upconversion emission, high-order multiphoton UV upconversion has attracted much attention and has been applied in the frontier fields of biological detection, [10][11][12][13][14] drug delivery, 6,15,16 optogenetics and photochemistry. 17,18 At present, most of the popular lanthanide-doped UCNPs with high-efficiency UV emission are focused in Yb 3+ -sensitized systems excited using a 980 nm laser, which seriously overlaps with the absorption of water and limits the penetration depth. 19,20 What's more, the resulting overheating effect will cause a certain degree of damage to cells and biological tissues.…”