The interconnection of microRNAs (miRNAs) and metal ions governs multiple biological processes in disease development and progression. However, developing multiplexed tools for dynamic imaging of these regulators remains a significant challenge. Herein, we report a conceptual approach for the design of an optically controlled DNA nanomachine by introducing a ternary DNAzyme-based, UV light-cleavable DNA scaffold and upconversion nanoparticle to the activatable hybrid chain reaction. We demonstrate that this nanomachine is capable of being effectively operated either in the presence of an endogenous miRNA target or the coexistence of intracellular Zn 2+ and external near-infrared light, resulting in enhanced fluorescence resonance energy transfer signals. With this design, the logic-gated imaging of endogenous miR-21 and Zn 2+ is demonstrated in living cells. More importantly, taking advantages of photoacoustic imaging modality, a combinational logic circuit (AND/OR) is constructed for the bioorthogonal cascade imaging of miR-21 and Zn 2+ in vivo, realizing dynamic monitoring of the correlation of miRNA and metal ions levels. Collectively, our results suggest that this conceptual design possesses the ability to expand the DNA nanomachine toolbox for visualizing a broad spectrum of interconnected molecules and thus provides new perspectives to improve the diagnostic and therapeutic outcomes.

Raman spectroscopy facilitates the study of reacting molecules on single nanomaterials. In recent years, the temporal resolution of Raman spectral measurement has been remarkably reduced to the millisecond level. However, the classic scan-based imaging mode limits the application in the dynamical study of reactions at multiple nanostructures. In this paper, we propose a spatiotemporal-resolved Raman spectroscopy (STRS) technology to achieve fast (∼40 ms) and high spatial resolution (∼300 nm) hyperspectral Raman imaging of single nanostructures. With benefits of the outstanding electromagnetic field enhancement factor by surface plasmon resonance (∼1012) and the snapshot hyperspectral imaging strategy, we demonstrate the observation of stepwise Raman signals from single-particle plasmon-assisted reactions. Results reveal that the reaction kinetics is strongly affected by not only the surface plasmon-polariton generation but also the density of Raman molecules. In consideration of the spatiotemporal resolving capability of STRS, we anticipate that it provides a potential platform for further extending the application of Raman spectroscopy methods in the dynamic study of 1D or 2D nanostructures.

Abstract. Targeted drug delivery system (DDS) means to selectively transport drugs to targeted tissues, organs, and cells through a variety of drugs carrier. It is usually designed to improve the pharmacological and therapeutic properties of conventional drugs and to overcome problems such as limited solubility, drug aggregation, poor bio distribution and lack of selectivity, controlling drug release carrier and to reduce normal tissue damage. With the characteristics of nontoxic and biodegradable, it can increase the retention of drug in lesion site and the permeability, improve the concentration of the drug in lesion site.at present, there are some kinds of DDS using at test phase, such as slow controlled release drug delivery system, targeted drug delivery systems, transdermal drug delivery system, adhesion dosing system and so on. This paper makes a review for DDS.

Orthogonal therapy that combines CRISPR-based gene editing and prodrug-based chemotherapy is a promising approach to combat multidrug-resistant cancer. However, its potency to precisely regulate different therapeutic modalities in vivo is...

The cGAS‐STING (cyclic GMP‐AMP synthase/stimulator of interferon genes) pathway is emerging as a promising target for cancer immunotherapy. However, developing specific and effective strategies for activating the cGAS‐STING pathway in tumors is still challenging. Here, a microRNA‐21 (miR‐21)‐responsive nucleic acid system, as a STING signal amplifier, is designed based on the branched catalytic hairpin assembly (bCHA). The effects of three types of dsDNA structures (linear dsDNA, Y scaffold dsDNA, and dsDNA dendrimer) on cGAS‐STING activation are systematically studied. This study demonstrates that dsDNA dendrimer can induce the most effective liquid–liquid phase separation in a miR‐21‐dependent manner, allowing the controllable activation of cGAS‐STING in both cancer cells and dendritic cells. Given the programmable nature of nucleic acid structure, this study will enable a readily accessible platform for integrating with immunotherapeutic strategies while opening new avenues for controllable, tumor‐specific activation of STING agonists.