Pulsatilla chinensis functions as a novel antihyperlipidemic agent by upregulating LDLR in an ERK-dependent manner.

Background: Pulsatilla chinensis (PC) is a traditional Chinese medicine (TCM) known for its beneficial activities. It has been historically used to treat dysentery, vaginal trichomoniasis, bacterial infections, and malignant tumors. The therapeutic potential of PC in the management of hypercholesterolemia remains largely unexplored.

Modulating the Gut Microbiota and Metabolites with Traditional Chinese Medicines: An Emerging Therapy for Type 2 Diabetes Mellitus and Its Complications.

Currently, an estimated 537 million individuals are affected by type 2 diabetes mellitus (T2DM), the occurrence of which is invariably associated with complications. Glucose-lowering therapy remains the main treatment for alleviating T2DM. However, conventional antidiabetic agents are fraught with numerous adverse effects, notably elevations in blood pressure and lipid levels.

Protease-Triggered, Spatially Controlled DNA Assembly in Apoptotic Cells for Early Evaluation of Therapeutic Efficacy.

Despite numerous advances in the use of DNA as building blocks to assemble complex structures, the dearth of strategies that allow for protease-controlled in situ DNA assembly in living cells remains a bottleneck in this field. Here, we present a modular engineering approach to achieve protease-triggered self-assembly of DNA in apoptotic cells for early evaluation of tumor response to drug treatment. In the design, peptide nucleic acid is introduced as a building bridge to engineer DNA building blocks with peptides and thus to suppress their self-assembly activity, while caspase-3 (Casp-3) protease-mediated enzymatic cleavage of the peptide substrate enables the activation of the DNA assembly, generating fluorescence signal output for real-time monitoring of Casp-3 activity.

Spatially resolved in vivo imaging of inflammation-associated mRNA via enzymatic fluorescence amplification in a molecular beacon.

The in vivo optical imaging of RNA biomarkers of inflammation is hindered by low signal-to-background ratios, owing to non-specific signal amplification in healthy tissues. Here we report the design and in vivo applicability, for the imaging of inflammation-associated messenger RNAs (mRNAs), of a molecular beacon bearing apurinic/apyrimidinic sites, whose amplification of fluorescence is triggered by human apurinic/apyrimidinic endonuclease 1 on translocation from the nucleus into the cytoplasm specifically in inflammatory cells. We assessed the sensitivity and tissue specificity of an engineered molecular beacon targeting interleukin-6 (IL-6) mRNA in live mice, by detecting acute inflammation in their paws and drug-induced inflammation in their livers.

Spatiotemporally Selective Molecular Imaging via Upconversion Luminescence-Controlled, DNA-Based Biosensor Technology.

DNA-based biosensor technologies have shown great potential in chemical and biological detection. These biosensors have been actively developed as probes for molecular imaging in live cells and in animals, allowing in situ detection of analytes in complex biological systems, elucidation of the roles of key molecules in biological processes, and the development of non-invasive diagnosis and image-guided surgery. Despite the progress made, improving the spatial-temporal precision remains a challenge in this field.

Mild Acidosis-Directed Signal Amplification in Tumor Microenvironment via Spatioselective Recruitment of DNA Amplifiers.

DNA biotechnology offers intriguing opportunities for amplification-based sensitive detection. However, spatiotemporally-controlled manipulation of signal amplification for in situ imaging of the tumor microenvironment remains an outstanding challenge. Here, we demonstrate a DNA-based strategy that can spatial-selectively amplify the acidic signal in the extracellular milieu of the tumor to achieve specific imaging with improved sensitivity.

Peptide Nucleic Acid (PNA)-Guided Peptide Engineering of an Aptamer Sensor for Protease-Triggered Molecular Imaging.

Protease-triggered control of functional DNA has remained unachieved, leaving a significant gap in activatable DNA biotechnology. Herein, we report the design of a protease-activatable aptamer system that can perform molecular sensing and imaging in a tumor-specific manner. The system is constructed by locking the structure-switching activity of an aptamer using a rationally designed PNA-peptide-PNA triblock copolymer.

One-Step Synthesis of Single-Stranded DNA-Bridged Iron Oxide Supraparticles as MRI Contrast Agents.

Despite progress on DNA-assembled nanoparticle (NP) superstructures, their complicated synthesis procedures hamper their potential biomedical applications. Here, we present an exceptionally simple strategy for the synthesis of single-stranded DNA (ssDNA) assembled FeO supraparticles (DFe-SPs) as magnetic resonance contrast agents. Unlike traditional approaches that assemble DNA-conjugated NPs via Watson-Crick hybridization, our DFe-SPs are formed with a high yield through one-step synthesis and assembly of ultrasmall FeO NPs via ssDNA-metal coordination bridges.

Core-shell gold nanorod@mesoporous-MOF heterostructures for combinational phototherapy.

Despite the increasing usage of porphyrinic metal-organic frameworks (MOFs) for combination therapy, the controlled encapsulation of inorganic nanoparticle-based therapeutics into such MOFs with specific structures has remained a major obstacle for improved tumor therapy. Here, we report the synthesis of a mesoporous MOF shell on the surface of gold nanorods (AuNRs), wherein a single AuNR is captured individually in single-crystalline MOFs with a controlled crystallographic orientation, for combinational phototherapy against solid tumors. The core-shell heterostructures have the benefits of a mesoporous structure and photoinduced singlet oxygen generation behavior characterized by the porphyrinic MOF shell, together with the plasmonic photothermal conversion characteristic of AuNRs.

An orthogonally regulatable DNA nanodevice for spatiotemporally controlled biorecognition and tumor treatment.

Despite the potential of nanodevices for intelligent drug delivery, it remains challenging to develop controllable therapeutic devices with high spatial-temporal selectivity. Here, we report a DNA nanodevice that can achieve tumor recognition and treatment with improved spatiotemporal precision under the regulation of orthogonal near-infrared (NIR) light. The nanodevice is built by combining an ultraviolet (UV) light-activatable aptamer module and a photosensitizer (PS) with up-conversion nanoparticle (UCNP) that enables the operation of the nanodevice with deep tissue-penetrable NIR light.

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

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 of tissue penetration of short-wavelength light and the oxygen-dependent mechanism that renders it inadequate for hypoxic tumors. Here, to combat such limitations, we rationally designed core-shell upconversion nanoparticle@porphyrinic MOFs (UCSs) for combinational therapy against hypoxic tumors.

Nd -Sensitized Upconversion Metal-Organic Frameworks for Mitochondria-Targeted Amplified Photodynamic Therapy.

Herein, we report the design and synthesis of a mitochondria-specific, 808 nm NIR light-activated photodynamic therapy (PDT) system based on the combination of metal-organic frameworks (MOFs) and upconversion photochemistry with an organelle-targeting strategy. The system was synthesized through the growth of a porphyrinic MOF on Nd -sensitized upconversion nanoparticles to achieve Janus nanostructures with further asymmetric functionalization of the surface of the MOF domain. The PDT nanoplatform allows for photosensitizing with 808 nm NIR light, which could effectively avoid the laser-irradiation-induced overheating effect.

NIR-light-mediated spatially selective triggering of anti-tumor immunity via upconversion nanoparticle-based immunodevices.

Immunomodulatory therapies are becoming a paradigm-shifting treatment modality for cancer. Despite promising clinical results, cancer immunotherapy is accompanied with off-tumor toxicity and autoimmune adverse effects. Thus, the development of smarter systems to regulate immune responses with superior spatiotemporal precision and enhanced safety is urgently needed.

An Acidic-Microenvironment-Driven DNA Nanomachine Enables Specific ATP Imaging in the Extracellular Milieu of Tumor.

Extracellular ATP is an emerging target for cancer treatment because it is a key messenger for shaping the tumor microenvironment (TME) and regulating tumor progression. However, it remains a great challenge to design biochemical probes for targeted imaging of extracellular ATP in the TME. A TME-driven DNA nanomachine (Apt-LIP) that permits spatially controlled imaging of ATP in the extracellular milieu of tumors with ultrahigh signal-to-background ratio is reported.

Engineering Multifunctional DNA Hybrid Nanospheres through Coordination-Driven Self-Assembly.

Developing simple and general approaches for the synthesis of nanometer-sized DNA materials with specific morphologies and functionalities is important for various applications. Herein, a novel approach for the synthesis of a new set of DNA-based nanoarchitectures through coordination-driven self-assembly of Fe ions and DNA molecules is reported. By fine-tuning the assembly, Fe-DNA nanospheres of precise sizes and controlled compositions can be produced.

Light-Activated Nanoprobes for Biosensing and Imaging.

Fluorescent nanoprobes are indispensable tools to monitor and analyze biological species and dynamic biochemical processes in cells and living bodies. Conventional nanoprobes have limitations in obtaining imaging signals with high precision and resolution because of the interference with biological autofluorescence, off-target effects, and lack of spatiotemporal control. As a newly developed paradigm, light-activated nanoprobes, whose imaging and sensing activity can be remotely regulated with light irradiation, show good potential to overcome these limitations.

Trace water mediated growth of oriented single-crystalline mesoporous metal-organic frameworks on gold nanorods.

Here we report, for the first time, the growth of single-crystalline mesoporous MOFs with well-controlled orientation on the surface of gold nanorods. Importantly, it showed that trace amounts of water could induce the formation of MOFs of different phases and shapes, which was critical for the synthesis of such mesoporous heterostructures.

Imparting Designer Biorecognition Functionality to Metal-Organic Frameworks by a DNA-Mediated Surface Engineering Strategy.

Surface functionality is an essential component for processing and application of metal-organic frameworks (MOFs). A simple and cost-effective strategy for DNA-mediated surface engineering of zirconium-based nanoscale MOFs (NMOFs) is presented, capable of endowing them with specific molecular recognition properties and thus expanding their potential for applications in nanotechnology and biotechnology. It is shown that efficient immobilization of functional DNA on NMOFs can be achieved via surface coordination chemistry.

Upconversion Luminescence-Activated DNA Nanodevice for ATP Sensing in Living Cells.

Designer DNA nanodevices have attracted extensive interest for detection of specific targets in living cells. However, it still remains a great challenge to construct DNA sensing devices that can be activated at desired time with a remotely applied stimulus. Here we report a rationally designed, synthetic DNA nanodevice that can detect ATP in living cells in an upconversion luminescence-activatable manner.

Heterodimers Made of Upconversion Nanoparticles and Metal-Organic Frameworks.

Creating nanoparticle dimers has attracted extensive interest. However, it still remains a great challenge to synthesize heterodimers with asymmetric compositions and synergistically enhanced functions. In this work, we report the synthesis of high quality heterodimers composed of porphyrinic nanoscale metal-organic frameworks (nMOF) and lanthanide-doped upconversion nanoparticles (UCNPs).