Engineering of Upconverted Metal–Organic Frameworks for Near-Infrared Light-Triggered Combinational Photodynamic/Chemo-/Immunotherapy against Hypoxic Tumors

Journal of the American Chemical Society, Год журнала: 2020, Номер 142(8), С. 3939 - 3946

Опубликована: Янв. 23, 2020

Metal-organic frameworks (MOFs) have shown great potential as nanophotosensitizers (nPSs) for photodynamic therapy (PDT). The use of such MOFs in PDT, however, is limited by the shallow depth tissue penetration short-wavelength light and oxygen-dependent mechanism that renders it inadequate hypoxic tumors. Here, to combat limitations, we rationally designed core-shell upconversion nanoparticle@porphyrinic (UCSs) combinational against UCSs were synthesized high yield through conditional surface engineering UCNPs subsequent seed-mediated growth strategy. heterostructure allows efficient energy transfer from UCNP core MOF shell, which enables near-infrared (NIR) light-triggered production cytotoxic reactive oxygen species. A hypoxia-activated prodrug tirapazamine (TPZ) was encapsulated nanopores shell heterostructures final construct TPZ/UCSs. We demonstrated TPZ/UCSs represent a promising system achieving improved cancer treatment vitro vivo via combination NIR light-induced PDT chemotherapy. Furthermore, integration nanoplatform with antiprogrammed death-ligand 1 (α-PD-L1) promotes abscopal effect completely inhibit untreated distant tumors generating specific tumor infiltration T cells. Collectively, this work highlights robust combining chemotherapy immunotherapy current limitations treatment.

Язык: Английский

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Nd³⁺‐Sensitized Upconversion Metal–Organic Frameworks for Mitochondria‐Targeted Amplified Photodynamic Therapy

Angewandte Chemie International Edition, Год журнала: 2019, Номер 59(7), С. 2634 - 2638

Опубликована: Ноя. 21, 2019

Abstract Herein, we report the design and synthesis of a mitochondria‐specific, 808 nm NIR light‐activated photodynamic therapy (PDT) system based on combination metal–organic frameworks (MOFs) upconversion photochemistry with an organelle‐targeting strategy. The was synthesized through growth porphyrinic MOF Nd 3+ ‐sensitized nanoparticles to achieve Janus nanostructures further asymmetric functionalization surface domain. PDT nanoplatform allows for photosensitizing light, which could effectively avoid laser‐irradiation‐induced overheating effect. Furthermore, mitochondria‐targeting amplify efficacy depolarization mitochondrial membrane initiation intrinsic apoptotic pathway. This work sheds light hybrid engineering MOFs combat their current limitations PDT.

Язык: Английский

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Nucleic Acid Tests for Clinical Translation

Chemical Reviews, Год журнала: 2021, Номер 121(17), С. 10469 - 10558

Опубликована: Июль 13, 2021

Nucleic acids, including deoxyribonucleic acid (DNA) and ribonucleic (RNA), are natural biopolymers composed of nucleotides that store, transmit, express genetic information. Overexpressed or underexpressed as well mutated nucleic acids have been implicated in many diseases. Therefore, tests (NATs) extremely important. Inspired by intracellular DNA replication RNA transcription, vitro NATs extensively developed to improve the detection specificity, sensitivity, simplicity. The principles can be general classified into three categories: hybridization, thermal-cycle isothermal amplification, signal amplification. Driven pressing needs clinical diagnosis prevention infectious diseases, evolved a rapidly advancing field. During past ten years, an explosive increase research interest both basic translation has witnessed. In this review, we aim provide comprehensive coverage progress analyze use recognition probes, construct devices based on utilize other important fields. We also discuss new frontiers field challenges addressed.

Язык: Английский

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Organelle‐Specific Photoactivation of DNA Nanosensors for Precise Profiling of Subcellular Enzymatic Activity

Angewandte Chemie International Edition, Год журнала: 2021, Номер 60(16), С. 8923 - 8931

Опубликована: Янв. 22, 2021

Understanding of the functions enzymes in diverse cellular processes is important, but design sensors with controllable localization for situ imaging subcellular levels enzymatic activity particularly challenging. We introduce herein a spatiotemporally controlled sensor technology that permits and photoactivated human apurinic/apyrimidinic endonuclease 1 (APE1) within an intracellular organelle choice (e.g., mitochondria or nucleus). The hybrid platform constructed by photoactivatable engineering DNA-based fluorescent probe further combination upconversion nanoparticle specific signal. Controlled NIR-light-mediated photoactivation "on demand" effectively constrains signal to interest, improved resolution. demonstrate application nanosensors APE1 translocation response oxidative stress live cells.

Язык: Английский

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Near-Infrared Light Controllable DNA Walker Driven by Endogenous Adenosine Triphosphate for in Situ Spatiotemporal Imaging of Intracellular MicroRNA

ACS Nano, Год журнала: 2021, Номер 15(9), С. 14253 - 14262

Опубликована: Авг. 19, 2021

As a powerful signal amplification tool, the DNA walker has been widely applied to detect rare microRNA (miRNA) in vivo. Despite significant advances, near-infrared (NIR) light controllable for powered by an endogenous initiator not realized, which is crucial spatiotemporal imaging of miRNA living cells with high sensitivity. Herein, we constructed NIR-photoactivatable system, was adenosine triphosphate (ATP) situ spatial and temporal resolution. The system very stable extremely low fluorescent background bioimaging cells. We employed upconversion nanoparticles (UCNPs) as carriers probe transducers converting NIR UV light. Coupled fueled intracellular ATP, smart based on initiated successfully developed precise control Triggered light, could autonomously progressively travel along track assistance ATP. different cell lines highly This strategy can expand photocontrol biological system.

Язык: Английский

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Spatially Selective Imaging of Mitochondrial MicroRNAs via Optically Programmable Strand Displacement Reactions

Angewandte Chemie International Edition, Год журнала: 2021, Номер 60(33), С. 17937 - 17941

Опубликована: Июнь 12, 2021

Abstract MicroRNA (miRNA) functions are tightly regulated by their sub‐compartmental location in living cells, and the ability to imaging of mitochondrial miRNAs (mitomiRs) is essential for understanding related pathological processes. However, most existing DNA‐based methods could not be used this purpose. Here, we report development a DNA nanoreporter technology mitomiRs cells through near‐infrared (NIR) light‐controlled strand displacement reactions. The sensing function nanoreporters silent (OFF) during delivery process, but can photoactivated (ON) with NIR light after targeted localization, enabling spatially‐restricted two types cancer‐related improved detection accuracy. Furthermore, demonstrate vivo spatiotemporally‐controlled activation. Therefore, study illustrates simple methodology that may broadly applicable investigating mitomiRs‐associated physiological events.

Язык: Английский

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Construction of an Autocatalytic Hybridization Assembly Circuit for Amplified In Vivo MicroRNA Imaging

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(19)

Опубликована: Янв. 25, 2022

Lowly expressed analyte in complex cytoplasmic milieu necessitates the development of non-enzymatic autocatalytic DNA circuits with high amplification and anti-interference performance. Herein, we engineered a versatile robust stimuli-responsive hybridization assembly (AHA) circuit for high-performance vivo bioanalysis. Under moderately confined condition, initiator motivated autonomous cooperative cross-activation cascade reaction catalytic generating an exponentially amplified readout without parasite steric hindrance random diffusion side effects. The AHA was systematically investigated by series experimental studies theoretical simulations. successively guaranteed target recognition synergistically accelerated signal-amplification enabled sensitive selective detection analyte, realized miRNA imaging living cells mice. This could substantially expand toolbox accurate diagnosis programmable therapeutics.

Язык: Английский

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Advanced Near‐Infrared Light for Monitoring and Modulating the Spatiotemporal Dynamics of Cell Functions in Living Systems

Advanced Science, Год журнала: 2020, Номер 7(8)

Опубликована: Фев. 27, 2020

Abstract Light‐based technique, including optical imaging and photoregulation, has become one of the most important tools for both fundamental research clinical practice, such as cell signal sensing, cancer diagnosis, tissue engineering, drug delivery, visual regulation, neuromodulation, disease treatment. In particular, low energy near‐infrared (NIR, 700–1700 nm) light possesses lower phototoxicity higher penetration depth in living systems compared with ultraviolet/visible light, making it a promising tool vivo applications. Currently, NIR light‐based photoregulation strategies have offered possibility to real‐time sense and/or modulate specific cellular events deep tissues subcellular accuracy. Herein, recent progress respect monitoring modulating spatiotemporal dynamics functions are summarized. applications techniques theranostics, regenerative medicine, neuroscience systematically introduced discussed. addition, challenges prospects sensing regulating comprehensively

Язык: Английский

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The Recent Development of Hybridization Chain Reaction Strategies in Biosensors

ACS Sensors, Год журнала: 2020, Номер 5(10), С. 2977 - 3000

Опубликована: Сен. 18, 2020

With the continuous development of biosensors, researchers have focused increasing attention on various signal amplification strategies to pursue superior performance for more applications. In comparison with other strategies, hybridization chain reaction (HCR) as a powerful technique shows its certain charm owing nonenzymatic and isothermal features. Recently, basis conventional HCR, this has been developed improved rapidly, variety HCR-based biosensors excellent reported. Herein, we present systematic critical review research progress HCR in last five years, including newly such multibranched migration localized situ netlike so on, well combination techniques, nanomaterials, functional DNA molecules. By illustrating some representative works, also summarize advantage challenge offer deep discussion latest future trends biosensors.

Язык: Английский

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Activating a DNA Nanomachine via Computation across Cancer Cell Membranes for Precise Therapy of Solid Tumors

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(37), С. 15233 - 15242

Опубликована: Сен. 13, 2021

Taking advantage of cancer cells' endogenous characters, the responsive activation DNA nanomachines has achieved great success in tumor therapy. Combining with extra stimuli such as external light irradiation provided spatiotemporal control nanomachine activation. However, specific at cellular level is still challenging considering macroscopic-scale exposure area usual sources. logic gates located cell membrane contributed to specificity, but free diffusion input strands during operation process would impair efficiency and result side effects circumjacent normal cells solid tumors. Here we design a transmembrane logical computation strategy activate only from complex microenvironment. The multishell UCNPs-DNA prepared by modifying on upconversion nanoparticles. LA-apt, strand anchoring overexpressed receptor, intracellular miRNA-21 served inputs 1 2, respectively. Hybridization not exposes recognition region nanomachine, also delivers it into cells. cascade hybridization 2 completes "AND" gate releases L2 output. acts trigger operate correspondingly activates photosensitizer Rose Bengal for reactive oxygen species generation. Through across membrane, highly precise therapy microenvironment, which could become promising modality

Язык: Английский

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