A Multifunctional Peptide Nucleic Acid/Peptide Copolymer-Based Dual-Mode Biosensor with Macrophage-Hitchhiking for Enhanced Tumor Imaging and Urinalysis.

Biosensors are capable of diagnosing tumors through imaging or liquid biopsy, but they face the challenges of inefficient delivery into tumor sites and the lack of reliable tumor-associated biomarkers. Herein, we constructed a dual-mode biosensor based on a multifunctional peptide nucleic acid (PNA)/peptide copolymer and DNA tetrahedron for tumor imaging and urinalysis. The biosensor could enter the cancer cells to initiate a microRNA-21-specific catalytic hairpin assembly reaction after cleavage by matrix-metalloprotease (MMP) in the tumor microenvironment, and the MMP cleavage product was released into the bloodstream and then was filtered out by the kidney.

DNA nanodevice as a multi-module co-delivery platform for combination cancer immunotherapy.

A major challenge in combining cancer immunotherapy is the efficient delivery of multiple types of immunological stimulators to elicit a robust anti-tumor immune response and reprogram the immunosuppressive tumor microenvironment (TME). Here, we developed a DNA nanodevice that was generated by precisely assembling three types of immunological stimulators. The doxorubicin (Dox) component induced immunogenic cell death (ICD) in tumor cells and enhanced phagocytosis of antigen-presenting cells (APCs).

A DNA Logic Circuit Equipped with a Biological Amplifier Loaded into Biomimetic ZIF-8 Nanoparticles Enables Accurate Identification of Specific Cancers In Vivo.

DNA logic circuits (DLC) enable the accurate identification of specific cell types, such as cancer cells, but they face the challenges of weak output signals and a lack of competent platforms that can efficiently deliver DLC components to the target site in the living body. To address these issues, we rationally introduced a cascaded biological amplifier module based on the Primer Exchange Reaction inspired by electronic circuit amplifier devices. As a paradigm, three abnormally expressed Hela cell microRNAs (-30a, -17, and -21) were chosen as "AND" gate inputs.

Neutrophil-Membrane-Coated Biomineralized Metal-Organic Framework Nanoparticles for Atherosclerosis Treatment by Targeting Gene Silencing.

Antisense oligonucleotides (ASOs) are promising tools for gene silencing and have been exploited as therapeutics for human disease. However, delivery of therapeutic ASOs to diseased tissues or cells and subsequent escape from the endosomes and release of ASO in the cytosol remain a challenge. Here, we reported a neutrophil-membrane-coated zeolitic imidazolate framework-8 (ZIF-8) nanodelivery platform (AM@ZIF@NM) for the targeted transportation of ASOs against microRNA-155 (anti-miRNA-155) to the endothelial cells in atherosclerotic lesions.

Simultaneous Imaging and Visualizing the Association of Survivin mRNA and Telomerase in Living Cells by Using a Dual-Color Encoded DNA Nanomachine.

Simultaneous imaging and especially visualizing the association of survivin mRNA and telomerase in living cells are of great value for the diagnosis and prognosis of cancer because their co-expression facilitates the development of cancer and identifies patients at high risk of tumor-related death. The challenge is to develop methods that enable visualizing the association of multiplex targets and avoid the distorted signals due to the different delivery efficiency of probes. Herein, we engineered a DNA triangular prism nanomachine (DTPN) for simultaneous multicolor imaging of survivin mRNA and telomerase and visualizing their association in living cells.

Erythrocyte-Membrane-Enveloped Biomineralized Metal-Organic Framework Nanoparticles Enable Intravenous Glucose-Responsive Insulin Delivery.

A "closed-loop" insulin delivery system that can mimic the dynamic and glucose-responsive insulin secretion as islet β-cells is desirable for the therapy of type 1 and advanced type 2 diabetes mellitus (T1DM and T2DM). Herein, we introduced a kind of "core-shell"-structured glucose-responsive nanoplatform to achieve intravenous "smart" insulin delivery. A finely controlled one-pot biomimetic mineralization method was utilized to coencapsulate insulin, glucose oxidase (GOx), and catalase (CAT) into the ZIF-8 nanoparticles (NPs) to construct the "inner core", where an efficient enzyme cascade system (GOx/CAT group) served as an optimized glucose-responsive module that could rapidly catalyze glucose to yield gluconic acid to lower the local pH and effectively consume the harmful byproduct hydrogen peroxide (HO), inducing the collapse of pH-sensitive ZIF-8 NPs to release insulin.

mRNA-Activated Multifunctional DNAzyme Nanotweezer for Intracellular mRNA Sensing and Gene Therapy.

Deoxyribozyme (DNAzyme) is regarded as a promising gene therapy drug. However, poor cellular uptake efficacy and low biological stability limit the utilization of DNAzyme in gene therapy. Here, we report a well-known programmable DNAzyme-based nanotweezer (DZNT) that provides a new strategy for the detection of TK1 mRNA and survivin mRNA-targeted gene silencing therapy.

Biomineralized metal-organic framework nanoparticles enable a primer exchange reaction-based DNA machine to work in living cells for imaging and gene therapy.

Sensitive tumor imaging and precise tumor therapy play critical roles in the cancer combat. Herein, we build a DNA machine based on a primer exchange reaction (PER) for mRNA imaging and gene therapy. By using zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) to co-deliver the components including a primer, hairpin and strand displacing polymerase to the living cells, the PER-based DNA machine can be initiated by intracellular survivin mRNA and continuously produce Bcl-2 antisense DNA (ASD), which enables the DNA machine not only to image survivin mRNA but also to implement gene therapy.

Engineering a Biodegradable Nanocarrier for Enhancing the Response of T98G Cells to Temozolomide.

Temozolomide (TMZ), the most common DNA alkylating agent, is predominantly mediated by O-methylguanine DNA lesions for the treatment of glioblastoma (GBM). When O-methylguanine-DNA methyltransferase (MGMT) is present, TMZ-induced O-methylguanine lesions are repaired, resulting in the emergence of resistance to chemotherapy. Herein, we attempted to enhance the response of T98G cells to TMZ by gene silencing of MGMT.

A photocontrolled and self-powered bipedal DNA walking machine for intracellular microRNA imaging.

In this work, we report a photocontrolled and self-powered DNA walking machine with bipedal DNAzyme walkers for intracellular microRNA imaging.

An RNase H-powered DNA walking machine for sensitive detection of RNase H and the screening of related inhibitors.

Ribonuclease H (RNase H), an intracellular ribonuclease, plays a crucial role in cellular processes and especially relates to many disease processes. Here, we report a novel signal amplification strategy based on an RNase H-powered DNA walking machine for specific and sensitive RNase H activity detection. The DNA walking machine is composed of a small quantity of DNA walker strands and abundant FAM-labeled DNA-RNA chimeric strands on a single gold nanoparticle (AuNP).

An enzyme-initiated DNAzyme motor for RNase H activity imaging in living cell.

In this work, we have developed a novel DNAzyme motor initiated by endogenous enzyme for sensitive imaging of intracellular RNase H activity.

Aptamer-Functionalized DNA Origami for Targeted Codelivery of Antisense Oligonucleotides and Doxorubicin to Enhance Therapy in Drug-Resistant Cancer Cells.

Drug resistance is a major obstacle to the efficient therapy of drug-resistant cancer. To overcome this problem, we constructed a multifunctional DNA origami-based nanocarrier for codelivery of a chemotherapeutic drug (doxorubicin, Dox) and two different antisense oligonucleotides (ASOs; B-cell lymphoma 2 (Bcl2) and P-glycoprotein (P-gp)) into drug-resistant cancer cells for enhanced therapy. To increase the targeting ability of origami, staple strands with 5'-end extended MUC1 sequences were used in the preparation of aptamer-functionalized origami carrying ASOs (Apt-origami-ASO).

Molecular Switching of a Self-Assembled 3D DNA Nanomachine for Spatiotemporal pH Mapping in Living Cells.

DNA nanomachines have received great interest due to their potential to mimic various natural biomolecular machines. Intracellular pH sensing and imaging are of great significance to understand cellular behaviors and disease diagnostics. In this work, we report the novel molecular switching of a self-assembled 3D DNA triangular prism nanomachine (TPN) for pH sensing and imaging in living cells.

Biomineralized Metal-Organic Framework Nanoparticles Enable Enzymatic Rolling Circle Amplification in Living Cells for Ultrasensitive MicroRNA Imaging.

The enzymatic amplification strategy in living cells faces challenges of highly efficient intracellular codelivery of amplification reagents including DNA polymerase. In this work, we develop biomineralized metal-organic framework nanoparticles (MOF NPs) as a carrier system for intracellular codelivery of ϕ29 DNA polymerase (ϕ29DP) and nucleic acid probes and realize a polymerization amplification reaction in living cells. A pH-sensitive biodegradable MOF NP of zeolitic imidazolate framework-8 (ZIF-8) is utilized to encapsulate ϕ29DP and adsorb nucleic acid probes.

Target-assisted self-cleavage DNAzyme probes for multicolor simultaneous imaging of tumor-related microRNAs with signal amplification.

In this work, we have developed a novel and highly selective signal amplification strategy based on target-assisted self-cleavage DNAzyme probes for multicolor and simultaneous imaging of miRNA-222 and miRNA-223 in living cells. The fluctuation of miRNA-222 and miRNA-223 expression levels could also be monitored.

In Situ Synthesis of Ultrathin ZIF-8 Film-Coated MSNs for Codelivering Bcl 2 siRNA and Doxorubicin to Enhance Chemotherapeutic Efficacy in Drug-Resistant Cancer Cells.

Multiple drug resistance is a persistent obstacle for efficient chemotherapy of cancer. Herein, we report a novel drug delivery platform. A zeolitic imidazole framework-8 (ZIF-8) film with a few nanometer thickness was in situ synthesized on the surface of carboxylated mesoporous silica (MSN-COOH) nanoparticles (NPs) for pore blocking and efficient loading of small interfering RNAs to fabricate a pH-responsive drug delivery system.