Detecting telomerase activity at the single-cell level using a CRISPR-Cas12a-based chip.

The intimate association between telomerase activity and cancer has driven the exploration of diverse methodologies for its precise detection. However, detecting telomerase activity at the single-cell level remains a significant challenge. Herein, we present a MOF-DNA barcode-amplified CRISPR-Cas12a strategy integrated with a single-cell microfluidic chip for ultrasensitive detection of telomerase activity.

Self-Metallized Whole Cell Vaccines Prepared by Microfluidics for Bioorthogonally Catalyzed Antitumor Immunotherapy.

Tumor whole cell, carrying a complete set of tumor-associated antigens and tumor-specific antigens, has shown great potential in the construction of tumor vaccines but is hindered by the complex engineering means and limited efficacy to cause immunity. Herein, we provided a strategy for the self-mineralization of autologous tumor cells with palladium ions in microfluidic droplets, which endowed the engineered cells with both immune and catalytic functions, to establish a bioorthogonally catalytic tumor whole-cell vaccine. This vaccine showed strong inhibition both in the occurrence and recurrence of tumor by invoking the immediate antitumor immunity and building a long-term immunity.

Self-Generating Gold Nanocatalysts in Autologous Tumor Cells for Targeted Catalytic Immunotherapy.

Employing tumor whole cells for tumor immunotherapy is a promising tumor therapy proposed in the early stage, but its therapeutic efficacy is weakened by the methods of eliminating pathogenicity and the mass ratio of the effective antigen carried by itself. Here, by adding gold ion to live cancer cells in the microfluidic droplets, this work obtains dead tumor whole cells with NIR-controlled catalytic ability whose pathogenicity is removed while plenary tumor antigens, major structure, and homing ability are reserved. The engineered tumor cell (Cell-Au) with the addition of prodrug provides O in an O-free Russell mechanism, which serves better in a hypoxic tumor microenvironment.

Erratum: Author correction to "Tumor-microenvironment activated duplex genome-editing nanoprodrug for sensitized near-infrared titania phototherapy" [Acta Pharm Sin B (2022) 4224-4234].

[This corrects the article DOI: 10.1016/j.apsb.

Logic-gated tumor-microenvironment nanoamplifier enables targeted delivery of CRISPR/Cas9 for multimodal cancer therapy.

Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies. However, the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression. Here, we propose a self-amplifying logic-gated gene editing strategy for gene/HO-mediated/starvation multimodal cancer therapy.

A Nanoinhibitor Targeting cGAS-STING Pathway to Reverse the Homeostatic Imbalance of Inflammation in Psoriasis.

Psoriasis is a chronic skin inflammation characterized by dysregulated crosstalk between immune cells and keratinocytes. Here we show that the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is a key regulator of psoriatic inflammation in a mouse model. Platinum-doped positively charged carbon dots (Pt-CDs) were designed to inhibit the cGAS-STING pathway.

Biodegradable Hollow Nanoscavengers Restore Liver Functions to Reverse Insulin Resistance in Type 2 Diabetes.

Type 2 diabetes (T2D) results from the cells' insulin resistance, and to date, insulin therapy and diabetes medications targeting glycemic management have failed to reverse the increase in T2D prevalence. Restoring liver functions to improve hepatic insulin resistance by reducing oxidative stress is a potential strategy for T2D treatment. Herein, the liver-targeted biodegradable silica nanoshells embedded with platinum nanoparticles (Pt-SiO) are designed as reactive oxygen species (ROS) nanoscavengers and functional hollow nanocarriers.

Glenohumeral joint trajectory tracking for improving the shoulder compliance of the upper limb rehabilitation robot.

Background: Exoskeletons have become an important tool to help patients with upper extremity motor dysfunction in rehabilitation training and life assistance. In the study of the upper limb exoskeleton, the human glenohumeral joint will produce accompanying movement during the movement of the shoulder joint. This phenomenon causes a positional deviation between the shoulder joint and the exoskeleton, which affects the accuracy of exoskeleton-assisted human movement and the wearing comfort.

In-Tumor Biosynthetic Construction of Upconversion Nanomachines for Precise Near-Infrared Phototherapy.

Targeted construction of therapeutic nanoplatforms in tumor cells with specific activation remains appealing but challenging. Here, we design a cancer-motivated upconversion nanomachine (UCNM) based on porous upconversion nanoparticles (p-UCNPs) for precise phototherapy. The nanosystem is equipped with a telomerase substrate (TS) primer and simultaneously encapsulates 5-aminolevulinic acid (5-ALA) and d-arginine (d-Arg).

Metal-Organic Framework-DNA Bio-Barcodes Amplified CRISPR/Cas12a Assay for Ultrasensitive Detection of Protein Biomarkers.

CRISPR/Cas12a shows excellent potential in disease diagnostics. However, insensitive signal conversion strategies hindered its application in detecting protein biomarkers. Here, we report a metal-organic framework (MOF)-based DNA bio-barcode integrated with the CRISPR/Cas12a system for ultrasensitive detection of protein biomarkers.

Metal Organic Framework-Based Bio-Barcode CRISPR/Cas12a Assay for Ultrasensitive Detection of MicroRNAs.

CRISPR/Cas12a has shown great potential in molecular diagnostics, but its application in sensing of microRNAs (miRNAs) was limited by sensitivity and complexity. Here, we have sensitively and conveniently detected microRNAs by reasonably integrating metal-organic frameworks (OFs) based bioarcodes with CRISPR/as12a ssay (designated as MBCA). In this work, DNA-functionalized Zr-MOFs were designed as the converter to convert and amplify each miRNA target into activators that can initiate the -cleavage activity of CRISPR/Cas12a to further amplify the signal.

Tumor-microenvironment activated duplex genome-editing nanoprodrug for sensitized near-infrared titania phototherapy.

Near-infrared (NIR)-light-triggered nanomedicine, including photodynamic therapy (PDT) and photothermal therapy (PTT), is growing an attractive approach for cancer therapy due to its high spatiotemporal controllability and minimal invasion, but the tumor eradication is limited by the intrinsic anti-stress response of tumor cells. Herein, we fabricate a tumor-microenvironment responsive CRISPR nanoplatform based on oxygen-deficient titania (TiO ) for mild NIR-phototherapy. In tumor microenvironment, the overexpressed hyaluronidase (HAase) and glutathione (GSH) can readily destroy hyaluronic acid (HA) and disulfide bond and releases the Cas9/sgRNA from TiO to target the stress alleviating regulators, , nuclear factor E2-related factor 2 (NRF2) and heat shock protein 90 (HSP90), thereby reducing the stress tolerance of tumor cells.

Activation of the cGAS-STING pathway combined with CRISPR-Cas9 gene editing triggering long-term immunotherapy.

Effective activation of cGAS-STING pathway combined with immune checkpoint blockade (ICB) within the immunosuppressive tumor microenvironment to induce stronger immune responsiveness yet remains challenging. CRISPR-Cas9 gene editing technology, which offers the benefits of permanence and irreversibility, could recognize the target genome sequence with sgRNA (Guide RNA) and guide the Cas9 protease to knock down the target gene. Herein, a nanoplatform (HMnMPH) for dual activation of cGAS-STING pathway in combination with CRISPR-Cas9 gene editing to silence programmed death ligand 1 (PD-L1) to trigger long-term immunotherapy was reported.

Multistage-Responsive Gene Editing to Sensitize Ion-Interference Enhanced Carbon Monoxide Gas Therapy.

As a promising therapeutic modality targeting cancer, gas therapy still faces critical challenges, especially in enhancing therapeutic efficacy and avoiding gas poisoning risks. Here, a pH/glutathione (GSH) dual stimuli-responsive CRISPR/Cas9 gene-editing nanoplatform combined with calcium-enhanced CO gas therapy for precise anticancer therapy, is established. In the tumor microenvironment (TME), the fast biodegradation of the CaCO layer via pH-induced hydrolyzation allows glucose oxidase (GOx) to catalyze glucose for H O production, which further reacts with manganese carbonyl (MnCO) and achieves the precise release of CO gas.

Hollow covalent organic framework-sheltering CRISPR/Cas12a as an in-vivo nanosensor for ATP imaging.

In addition to applications in genome editing, clustered regularly interspaced short palindromic repeats (CRISPR) have recently been engineered for medical diagnostics based on their trans-cleavage activity owing to their high base resolution and isothermal signal amplification. However, trans-cleavage activity is too fragile to be applied in vivo. Herein, we introduce a hollow covalent organic framework (COF)-sheltering CRISPR/aptamer-based sensor (h-CCS) for ATP imaging in living animals.

Hypoxia-Responsive Platinum Supernanoparticles for Urinary Microfluidic Monitoring of Tumors.

Cancer has become a leading cause of morbidity and mortality, and there is an increasing need for versatile tools to enable sensitive, simple and early cancer monitoring. Here, we report platinum supernanoparticles as an exogenous nanosensor which can dissociate into ultrasmall platinum nanoclusters (PtNCs) under tumor-specific hypoxia conditions. The resulting PtNCs can be filtered through the kidney as urinary reporters to be quantified by a companion volumetric bar-chart chip (V-Chip) for point-of-care analysis.

Hypoxia-Responsive Gene Editing to Reduce Tumor Thermal Tolerance for Mild-Photothermal Therapy.

Near-infrared (NIR)-light-triggered photothermal therapy (PTT) is usually associated with undesirable damage to healthy organs nearby due to the high temperatures (>50 °C) available for tumor ablation. Low-temperature PTT would therefore have tremendous value for clinical application. Here, we construct a hypoxia-responsive gold nanorods (AuNRs)-based nanocomposite of CRISPR-Cas9 for mild-photothermal therapy via tumor-targeted gene editing.

Nano-immunosorbent assay based on Cas12a/crRNA for ultra-sensitive protein detection.

Apart from the great potential in genome editing, the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas system has recently been widely used in biosensing. However, due to the complex and inefficient signal conversion strategies, most of the works focused on nucleic acid analysis rather than protein biomarkers. Herein, by employing DNA-AuNPs (gold nanoparticles) nanotechnology to activate trans-cleavage activity of CRISPR/Cas12a, a universal signal transduction strategy was established between trans-cleavage of CRISPR/Cas12a and protein analytes.

Recent near-infrared light-activated nanomedicine toward precision cancer therapy.

Light has been present throughout the history of mankind and even the universe. It is of great significance to human life, contributing to energy, agriculture, communication, and much more. In the biomedical field, light has been developed as a switch to control medical processes with minimal invasion and high spatiotemporal selectivity.

Mesopore to Macropore Transformation of Metal-Organic Framework for Drug Delivery in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic relapsing autoimmune disease that is characterized by segmental intestinal inflammation. There is an urgent need for more efficient inflammation-targeting strategies to improve therapeutic effect and reduce systemic drug exposure. Herein, an oxidation-responsive metal-organic framework material (Ce-MOF@PSS) is reported that preferentially adheres to inflamed intestine via enema.

Cerium metal organic framework mediated molecular threading for point-of-care colorimetric assays.

This work prepared a Cerium metal organic framework (Ce-MOF), which exhibits colorimetric and fluorescent response for HO simultaneously. The Ce-MOF was integrated in the origami paper SlipChip to directly analyze glucose and uric acid level in serum without sample handling or extra analytical equipment except for a smartphone. Its excellent stability in wide pH and temperature, which ranges from pH 1 to 12 and from 20 to 90 °C respectively, provides wider application prospects than conventional colorimetric strategy in the horseradish peroxidase (HRP) based detection.

The pharmacokinetic interaction between irinotecan and sunitinib.

The previous clinical trials found that the co-administration of irinotecan with sunitinib exhibited a synergistic antitumor effect. In the current study, we aimed to investigate whether the synergistic effect is related to a potential pharmacokinetic interaction between sunitinib and irinotecan. The inhibitory effects of sunitinib on SN-38 glucuronidation were determined by measuring the formation rates for SN38 glucuronide using recombinant human UGT isoforms and human liver microsomes (HLMs) in the absence or presence of sunitinib.

The label-free detection and distinction of CYP2C9-expressing and non-expressing cells by surface-enhanced Raman scattering substrates based on bimetallic AuNPs-AgNWs.

Cytochrome P450 2C9 (CYP2C9) is capable of catalyzing the biotransformation of endogenous compounds in cells, indicating that this enzyme could change the intracellular environment and is related to the pathogenesis of diseases. Currently, it is still a challenge to study the differences in cellular components between CYP2C9-expressing and non-expressing cells. In this study, employing a Au nanoparticles-Ag nanowires (AuNPs-AgNWs) decorated silicon wafer as a novel non-destructive and label-free tool, we applied surface-enhanced Raman scattering (SERS) spectroscopy to detect and distinguish the cellular composition of CYP2C9-expressing cells (293T-Mig-2C9) and non-expressing cells (293T-Mig-R1).

Near-infrared upconversion-activated CRISPR-Cas9 system: A remote-controlled gene editing platform.

As an RNA-guided nuclease, CRISPR-Cas9 offers facile and promising solutions to mediate genome modification with respect to versatility and high precision. However, spatiotemporal manipulation of CRISPR-Cas9 delivery remains a daunting challenge for robust effectuation of gene editing both in vitro and in vivo. Here, we designed a near-infrared (NIR) light-responsive nanocarrier of CRISPR-Cas9 for cancer therapeutics based on upconversion nanoparticles (UCNPs).