Exogenously and Endogenously Sequential Regulation of DNA Nanodevices Enables Organelle‐Specific Signal Amplification in Subcellular ATP Profiling

Angewandte Chemie International Edition, Год журнала: 2025, Номер unknown

Опубликована: Янв. 9, 2025

Abstract Adenosine triphosphate (ATP), the primary energy currency in cells, is dynamically regulated across different subcellular compartments. The ATP interplay between mitochondria and endoplasmic reticulum (ER) underscores their coordinated roles various biochemical processes, highlighting necessity for precise profiling of dynamics. Here we present an exogenously endogenously dual‐regulated DNA nanodevice spatiotemporally selective, subcellular‐compartment specific signal amplification sensing. system allows exogenous NIR light‐controlled spatiotemporal localization activation aptamer sensor or ER, while a endogenous enzyme organelles further drives via consumption molecular beacon fuels, resulting significantly enhanced sensitivity spatial precision organelle interest. Furthermore, demonstrate application this robust monitoring fluctuations ER following drug interventions. This advancement provides powerful tool improving our understanding cellular energetics at level holds potential development targeted therapeutics.

Язык: Английский

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Self‐Assembled DNA Nanospheres Driven by Carbon Dots for MicroRNAs Imaging in Tumor via Logic Circuit

Small, Год журнала: 2024, Номер 20(25)

Опубликована: Янв. 17, 2024

Abstract DNA nanostructures with diverse biological functions have made significant advancements in biomedical applications. However, a universal strategy for the efficient production of is still lacking. In this work, facile and mild method presented self‐assembling polyethylenimine‐modified carbon dots (PEI‐CDs) into nanospheres called CANs at room temperature. This makes universally applicable to multiple applications involving various types DNA. Due ultra‐small size strong cationic charge PEI‐CDs, exhibit dense structure high loading capacity encapsulated while providing excellent stability by protecting from enzymatic hydrolysis. Additionally, Mg 2+ incorporated form Mg@CANs which enriches performance enables subsequent imaging exogenous . Especially, DNAzyme logic gate system that contains AND OR constructed successfully delivered tumor cells vitro vivo. They can be specifically activated endogenic human apurinic/apyrimidinic endonuclease 1 recognize expression levels miRNA‐21 miRNA‐155 sites biocomputing. A versatile pattern delivery flexible circuits miRNAs are developed.

Язык: Английский

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A Self‐Cascade Oxygen‐Generating Nanomedicine for Multimodal Tumor Therapy

Small, Год журнала: 2024, Номер 20(44)

Опубликована: Июль 5, 2024

Natural and artificial enzyme oxygen-generating systems for photodynamic therapy (PDT) are developed tumor treatment, yet they have fallen short of the desired efficacy. Moreover, both enzymes photosensitizers usually need carriers efficient delivery to sites. Here, a self-cascade-enhanced multimodal is by ingeniously integrating PDT with Zn

Язык: Английский

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Recent Advances in Zeolitic Imidazolate Frameworks as Drug Delivery Systems for Cancer Therapy

Asian Journal of Pharmaceutical Sciences, Год журнала: 2025, Номер 20(1), С. 101017 - 101017

Опубликована: Янв. 10, 2025

Biological nanotechnologies based on functional nanoplatforms have synergistically catalyzed the emergence of cancer therapies. As a subtype metal-organic frameworks (MOFs), zeolitic imidazolate (ZIFs) exploded in popularity field biomaterials as excellent protective materials with advantages conformational flexibility, thermal and chemical stability, controllability. With these superior properties, applications ZIF-based combination various therapies for treatment grown rapidly recent years, showing remarkable achievements great potential. This review elucidates advancements use ZIFs drug delivery agents therapy. The structures, synthesis methods, modifiers used oncotherapy are presented. Recent advances application nanoparticles single or tumor treatments reviewed. Furthermore, future prospects, potential limitations, challenges nanomaterials discussed. We except to fully explore present clear outline their an effective help them achieve early clinical application.

Язык: Английский

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A Biomimetic Mineralization Strategy for the Long‐Term Preservation of Exosomes Through Non‐Destructive Encapsulation Within Zeolite Imidazolate Frameworks‐8

Small, Год журнала: 2025, Номер unknown

Опубликована: Март 19, 2025

Abstract Exosomes, which are extracellular vesicles derived from endosomes, play a crucial role in mediating intercellular communication and widely used medical diagnostics drug delivery. Conventional cryopreservation strategies can damage the integrity of exosomes, hindering their further application biomedical field. Here, novel approach is developed for exosome storage, shell intact exosomes holding (SHIELD), packages zeolite imidazolate frameworks‐8 (ZIF‐8) as protective shell. ZIF‐8 be quickly removed, meanwhile, inherent morphology biological function preserved, thereby mitigating potential biocompatible risks associated with ZIF‐8. Notably, SHIELD‐protected maintained cellular uptake capacity, 76% original protein content kept even after being stored one month. Overall, development SHIELD overcomes challenges traditional techniques preservation broadens applications exosomes.

Язык: Английский

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DNA Robots for CRISPR/Cas12a Activity Management and Universal Platforms for Biosensing

Analytical Chemistry, Год журнала: 2024, Номер 96(6), С. 2620 - 2627

Опубликована: Янв. 13, 2024

The CRISPR/Cas12a system is a revolutionary genome editing technique that widely employed in biosensing and molecular diagnostics. However, there are few reports on precisely managing the trans-cleavage activity of Cas12a by simple modification since traditional methods to manage often require difficult rigorous regulation core components. Hence, we developed novel regulatory mechanism, named DNA Robots for Enzyme Activity Management (DREAM), introducing two robots, apurinic/apyrimidinic site (AP site) or nick target activator. First, revealed mechanism how DREAM strategy regulated through different binding affinities. Second, was found improve selectivity identifying base mismatch. Third, modular biosensor excision repair enzymes based utilizing diversified generation ways multi-signal output platform such as fluorescence, colorimetry, visual lateral flow strip constructed. Furthermore, extended logic sensing circuits overcome barrier could not detect simultaneously single tube. Overall, only provided new prospects programmable systems but also enabled portable, specific, humanized detection with great potential

Язык: Английский

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Aptamer‐Based DNA Allosteric Switch for Regulation of Protein Activity

Advanced Science, Год журнала: 2024, Номер 11(30)

Опубликована: Июнь 12, 2024

Allostery is a fundamental way to regulate the function of biomolecules playing crucial roles in cell metabolism and proliferation deemed second secret life. Given limited understanding structure natural allosteric molecules, development artificial molecules brings huge opportunity transform mechanism into practical applications. In this study, concept bionics introduced design an DNA switch with activity site based on two aptamers for selective inhibition thrombin activity. Compared single aptamer, possesses significantly enhanced ability, which can be precisely regulated by converting states. Moreover, dynamic further subjected control threshold circuit realizing automatic concentration determination thrombin. These compelling results confirm that equipped self-sensing information-processing modules puts new slant research mechanisms application tactics chemical biomedical fields.

Язык: Английский

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Integration of STING activation and COX-2 inhibition via steric-hindrance effect tuned nanoreactors for cancer chemoimmunotherapy

Biomaterials, Год журнала: 2024, Номер 311, С. 122695 - 122695

Опубликована: Июнь 29, 2024

Язык: Английский

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Sequence-Unconstrained DNA Computing: DSN cycling and PER circuitry for dynamic miRNAs analysis and multifunctional logic operations

Chemical Engineering Journal, Год журнала: 2024, Номер unknown, С. 156045 - 156045

Опубликована: Сен. 1, 2024

Язык: Английский

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FRAME: flap endonuclease 1-engineered PAM module for precise and sensitive modulation of CRISPR/Cas12a trans-cleavage activity

Nucleic Acids Research, Год журнала: 2024, Номер 52(19), С. 11884 - 11894

Опубликована: Сен. 24, 2024

Abstract CRISPR/Cas12a system, renowned for its precise recognition and efficient nucleic acid cleavage capabilities, has demonstrated remarkable performance in molecular diagnostics biosensing. However, the reported Cas12a activity regulation methods often involved intricate CRISPR RNA (crRNA) structural adjustments or costly chemical modifications, which limited their applications. Here, we a unique enzyme engineering strategy using flap endonuclease 1 (FEN1) to regulate accessibility of protospacer adjacent motif (PAM) module double-stranded DNA activator (FRAME). By identifying three-base overlapping structure between target inputs substrate, FEN1 selectively cleaved released 5′-flap containing ‘TTTN’ sequence, triggered secondary while forming nicked PAM, ultimately achieving sensitive switching Cas12a’s activity. The FRAME exemplified ‘two birds with one stone’ principle, as it not only precisely programmed but also simultaneously isothermal cyclic amplification. Moreover, was applied construct sensing platform detecting myeloperoxidase miR-155, high sensitivity specificity. Importantly, proved versatility multiple targets single crRNA without redesign. Collectively, opens up novel avenue modulating activity, promising immense potential realm medical diagnostics.

Язык: Английский

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