Glowing Octopus-Inspired Nanomachine: A Versatile Aptasensor for Efficient Capture, Imaging, Separation, and NIR-Triggered Release of Cancer Cells.

The separation and analysis of circulating tumor cells (CTCs) in liquid biopsy significantly facilitated clinical cancer diagnosis and personalized therapy. However, current methods face challenges in simultaneous efficient capturing, separation, and imaging of CTCs, and most of the devices cannot be reused/regenerated. We present here an innovative glowing octopus-inspired nanomachine (GOIN), capable of capturing, imaging, separating, and controlling the release of cancer cells from whole blood and normal cells. The GOIN comprises an aptamer-decorated magnetic fluorescent covalent organic framework (COF), which exhibits a strong affinity for nucleolin-overexpressed cancer cells through a multivalent binding effect. The captured cancer cells can be directly imaged using the intrinsic stable fluorescence of the COF layer in the GOIN. Employing magnet and NIR laser assistance enables easy separation and mild photothermal release of CTCs from the normal cells and the nanomachine without compromising cell viability. Moreover, the GOIN demonstrates a reusing capability, as the NIR-triggered CTC release is mild and nondestructive, allowing the GOIN to be reused at least three times.

A covalent organic framework-derived M1 macrophage mimic nanozyme for precise tumor-targeted imaging and NIR-II photothermal catalytic chemotherapy.

Nanoprobes for efficient tumor-targeted imaging and therapy are urgently needed for clinical tumor theranostics. Herein, inspired by the heterogeneity of the tumor microenvironment, we report a covalent organic framework (COF)-derived biomimetic nanozyme for precise tumor-targeted imaging and NIR-II photothermal-catalysis-enhanced chemotherapy (PTCEC). Using a crystalline nanoscale COF as the precursor, a peroxidase-like porous N-doped carbonous nanozyme (PNC) was obtained, which was cloaked with an M1 macrophage cell membrane (M1m) to create a multifunctional biomimetic nanoprobe for tumor-targeted imaging and therapy. The M1m coating enabled the nanoprobe to target cancer cells and tumor tissues for highly efficient tumor imaging and drug delivery. The peroxidase-like activity of the PNC allowed for the conversion of intratumoral H2O2 into toxic ˙OH that synergized with its NIR-II photothermal effect to strengthen the chemotherapy. Therefore, highly efficient tumor-targeted imaging and NIR-II PTCEC were realized with an M1 macrophage mimic nanoprobe. This work provides a feasible tactic for a biomimetic theranostic nanoprobe and will inspire the development of new bioactive nanomaterials for clinical tumor theranostic applications.

Stimuli-responsive probes for amplification-based imaging of miRNAs in living cells.

MicroRNAs (miRNAs) have emerged as important biomarkers in biomedicine and bioimaging due to their roles in various physiological and pathological processes. Real-time and in situ monitoring of dynamic fluctuation of miRNAs in living cells is crucial for understanding these processes. However, current miRNA imaging probes still have some limitations, including the lack of effective amplification methods for low abundance miRNAs bioanalysis and uncontrollable activation, leading to background signals and potential false-positive results. Therefore, researchers have been integrating activatable devices with miRNA amplification techniques to design stimuli-responsive nanoprobes for "on-demand" and precise imaging of miRNAs in living cells. In this review, we summarize recent advances of stimuli-responsive probes for the amplification-based imaging of miRNAs in living cells and discuss the future challenges and opportunities in this field, aiming to provide valuable insights for accurate disease diagnosis and monitoring.

A gold nanoparticle engineered metal-organic framework nanoreactor for combined ferroptosis and mild photothermal therapy.

We demonstrate a gold nanoparticle engineered metal-organic framework nanoreactor with photothermal, glucose oxidase-like and GSH-consuming performance to achieve the accumulation of hydroxyl radicals and the enhancement of the thermal sensitivity for combined ferroptosis and mild photothermal therapy.

Tumor-targeted nanoflowers regulate glutamine metabolism and amplify oxidative stress for synergistic therapy.

We designed and synthesized tumor-targeted nanoflowers to inhibit glutamine metabolism and amplify oxidative stress, which could synergistically suppress tumor growth.

Pt nanozyme-bridged covalent organic framework-aptamer nanoplatform for tumor targeted self-strengthening photocatalytic therapy.

Covalent organic frameworks (COFs) have emerged as a promising platform for nanomedicine, while developing multifunctional COF nanoplatforms remains challenging due to the lack of efficient strategies for COF modification. Herein, we propose a nanozyme bridging (NZB) strategy for COF functionalization. Platinum nanoparticles (Pt NPs) as catalase mimics were in situ grown on the surface of COF NPs without reducing their drug loading capacity (CP), and thiol-terminated aptamer was further densely decorated onto CP NPs via a stable Pt-S bond (CPA). Pt nanozyme engineering and aptamer functionalization rendered the nanoplatform with excellent photothermal conversion, tumor targeting, and catalase-like catalytic performances. Using clinical-approved photosensitizer indocyanine green (ICG) as a model drug, we fabricated a nanosystem (ICPA) for tumor-targeted self-strengthening therapy. ICPA can effectively accumulate into tumor tissue and relieve the hypoxia microenvironment by decomposing the overexpressed H2O2 and generating O2. Under monowavelength NIR light irradiation, the catalase-like catalytic and singlet oxygen generation activities of ICPA can be significantly strengthened, leading to admirable photocatalytic treatment effects against malignant cells as well as tumor-bearing mice in a self-strengthening manner.

COF-DNA Bicolor Nanoprobes for Imaging Tumor-Associated mRNAs in Living Cells.

Developing probes for the simultaneous detection of multiple tumor-associated mRNAs is beneficial for the precise diagnosis and early therapy of cancer. In this work, we prepared two COF-DNA bicolor probes at room temperature and freezing conditions and evaluated their performances in simultaneous imaging of intracellular tumor-associated mRNAs. By loading dye-labeled survivin- and TK1-mRNA recognition sequences on porphyrin COF NPs, nucleic acid-specific "off-on" nanoprobes were obtained. The nanoprobe prepared by the freezing method exhibits higher ssDNA loading density and better fluorescence quenching efficiency. Moreover, its signal-to-noise ratio is significantly higher than that prepared at room temperature, and the target recognition effect was unaffected. Significantly, the freezing-method-prepared nanoprobe has higher signal intensities in target-overexpressed cells compared to the room-temperature-prepared probe, while their signals in cells with low target expression are similar. Thus, the freezing-method-prepared nanoprobe is a promising tool for improved cancer diagnostic imaging. This work can offer new insights into the exploration of high-performance COF-based nanoprobes for multiple biomarker detection.

Multicolor Covalent Organic Framework-DNA Nanoprobe for Fluorescence Imaging of Biomarkers with Different Locations in Living Cells.

Precisely detecting biomarkers in living systems holds tremendous promise for disease diagnosis and monitoring. Herein, we developed a covalent organic framework (COF)-based tricolor fluorescent nanoprobe for simultaneously imaging biomarkers with different spatial locations in living cells. Briefly, a TAMRA-labeled survivin mRNA antisense nucleotide and a Cy5-labeled transmembrane glycoprotein mucin 1 (MUC1) aptamer were adsorbed on a nanoscale fluorescent COF. To enhance the interactions between COF nanoparticles (NPs) and nucleic acid molecules, a freezing method was employed for improving the nucleic acid loading density and ensuring detection performance. The fluorescence signals of dyes on DNAs were first quenched by the COF NPs. Internalization and distribution of the nanoprobes can be real-time visualized by the autofluorescence of COF NPs. In living cells, recognition between MUC1 with MUC1 aptamers causes fluorescence signal recovery of Cy5, while hybridization between survivin mRNA and its antisense DNA induces the signal recovery of TAMRA. Therefore, this COF-based multicolor nanoprobe could be employed for visualizing MUC1 on the cell membrane and survivin mRNA in the cytoplasm. Cancer cell-specific diagnostic imaging and monitoring of the process of cancer cell exosomes infecting normal cells using the nanoprobe were achieved. This work not only offers a versatile nanoprobe for bioanalysis but also provides new insights for developing novel COF-based nanoprobes.

Covalent Organic Framework-Based Spherical Nucleic Acid Probe with a Bonding Defect-Amplified Modification Strategy.

Developing spherical nucleic acids with new structures holds great promise for nanomedicine and bioanalytical fields. Covalent organic frameworks (COFs) are emerging promising materials with unique properties for a wide range of applications. However, devising COF-based spherical nucleic acid is challenging because methods for the preparation of functionalized COFs are still limited. We report here a bonding defect-amplified modification (BDAM) strategy for the facile preparation of functionalized COFs. Poly(acrylic acid) was employed as the defect amplifier to modify the surface of COF nanoparticles by the formation of amide bonds with amino residues, which successfully converted and amplified the residues into abundant reactive carboxyl groups. Then, amino terminal-decorated hairpin DNA was densely grafted onto the surface of COF nanoparticles (NPs) to give rise to a spherical nucleic acid probe (SNAP). A series of experiments and characterizations proved the successful preparation of the COF-based SNAP, and its application in specifically lighting up RNA biomarkers in living cells for cancer diagnostic imaging was demonstrated. Therefore, the COF-based SNAP is a promising candidate for biomedical applications and the proposed BDAM represents a useful strategy for the preparation of functionalized COFs for diverse fields.

Ultrathin functionalized covalent organic framework nanosheets for tumor-targeted photodynamic therapy.

We developed a modification-facilitated exfoliation strategy for the one-step preparation of ultrathin 2D functionalized covalent organic framework nanosheets (COF NSs). Hyaluronic acid-functionalized ultrathin porphyrin COF NSs (about 5-8 nm) with enhanced reactive oxygen species (ROS) generation effect were readily prepared for tumor-targeted photodynamic therapy.

Covalent organic framework-engineered polydopamine nanoplatform for multimodal imaging-guided tumor photothermal-chemotherapy.

A covalent organic framework (COF)-engineered polydopamine core-shell nanoplatform (PDA@COF) was developed. The ultrasmall pores and abundant functional sites of the COF endowed the nanoplatform with enhanced drug loading capacity and diminished drug leakage effect. Multimodal imaging-guided photothermal chemo-synergistic tumor-targeted therapy was realized after rational functionalization. This work offers new insights for developing COF-based multifunctional theranostic systems.

A biomimetic MOF nanoreactor enables synergistic suppression of intracellular defense systems for augmented tumor ablation.

A homotypic cancer cell membrane camouflaged MOF-based nanoreactor with the photothermal-starvation effect has been developed for synergistic suppression of intracellular defensive systems for enhanced cancer treatment.