Near-Infrared Photoresponsive Nanotransducers for Precise Regulation of Gene Expression

Abstract

Regulation of gene expression is conducive to understanding the physiological roles of specific genes and provides therapeutic potentials, which however still remains a great challenge. Nonviral carriers have some advantages for gene delivery compared to traditional physical delivery strategies, but they often fail to control the delivery of genes in targeting regions, and thus lead to off-target side effects. Although endogenous biochemical signal-responsive carriers have been used to improve the transfection efficiency, their selectivity and specificity are still poor because of the coexistence of biochemical signals in both normal tissues and disease sites. In contrast, light-responsive carriers can be adopted to precisely control gene transgenic behaviors at the specified locations and time, thus reducing the off-target gene editing at nontarget positions. Particularly, the near-infrared (NIR) light has better tissue penetration depth and lower phototoxicity than ultraviolet and visible light sources, showing great promise for intracellular gene expression regulation. In this review, we summarize the recent progress of NIR photoresponsive nanotransducers for precision regulation of gene expression. These nanotransducers can achieve controlled gene expression via three different mechanisms (photothermal activation, photodynamic regulation, and NIR photoconversion) to allow various applications, such as gene therapy of cancer, which will be discussed in detail. A conclusion and discussion of the challenges and outlook will be given at the end of this review.

Chiral Cell Nanomechanics Originated in Clockwise/Counterclockwise Biofunctional Microarrays to Govern the Nuclear Mechanotransduction of Mesenchymal Stem Cells

“…In particular, transcription cofactor YAP will give a response to biomechanical tension along with the stretched direction . YAP nuclear translocation may be related to cytoskeleton parallel stretch, FA kinase activation, and zyxin relocation by anisotropic cell nanomechanics. , Cell nanomechanics has been reported to suppress cell senescence and aging by the inhibition of cGAS-STING signaling due to YAP/TAZ mechanotransduction. , In addition, the nuclear shape is changed by cytoskeleton force to regulate chromatin remodeling and phenotype alternation. − Therefore, in this study, the nuclear DNA synthesis level could be regulated by the mechanotransduction from anisotropic YAP signaling and biased cell nanomechanics due to chiral FA formation and heterogeneous cytoskeleton assembly (Figure ).…”