Ionic current rectification (ICR) based nanopipettes allow accurate monitoring of cellular behavior in single living cells. Herein, we proposed a 30 nm nanopipette functionalized with G‐quadruplex ...DNAzyme as an efficient biomimetic recognizer for ROS generation at subcellular level via the changes of current–voltage relationship. Taking advantages of the ultra‐small tip, the nanopipette could penetrate into a single living cell repeatedly or keep measuring for a long time without compromising the cellular functions. Coupled with precision nanopositioning system, generation of ROS in mitochondria in response to cell inflammation was determined with high spatial resolution. Meanwhile, the changes of aerobic metabolism in different cell lines under drug‐induced oxidative stress were monitored continuously. We believe that the ICR‐nanopipette could be developed as a powerful approach for the study of cellular activities via electrochemical imaging in living cells.
Electrochemical imaging: An ionic current rectification (ICR) based nanopipette with a 30 nm nanotip was fabricated for continuous monitoring of aerobic metabolism processes in single living cells at subcellular level. The cells produced reactive oxygen species (ROS) in mitochondria. The inner surface of the nanopipette was functionalized with G‐quadruplex DNAzyme.
We report here a tumor‐pretargted theranostic approach for multimodality imaging‐guided synergistic cancer PDT by cascade alkaline phosphatase (ALP)‐mediated in situ self‐assembly and bioorthogonal ...inverse electron demand Diels–Alder (IEDDA) reaction. Using the enzymatic catalysis of ALP that continuously catalyses the dephosphorylation and self‐assembly of trans‐cyclooctene (TCO)‐bearing P‐FFGd‐TCO, a high density of fluorescent and magnetic TCO‐containing nanoparticles (FMNPs‐TCO) can be synthesized and retained on the membrane of tumor cells. They can act as ‘artificial antigens’ amenable to concurrently capture lately administrated tetrazine (Tz)‐decorated PS (775NP‐Tz) and carbonic anhydrase (CA) inhibitor (SA‐Tz) via the fast IEDDA reaction. This two‐step pretargeting process can further induce FMNPs‐TCO regrowth into microparticles (FMNPs‐775/SA) directly on tumor cell membranes, which is analyzed by bio‐SEM and fluorescence imaging. Thus, efficient enrichment of both SA‐Tz and 775NP‐Tz in tumors can be achieved, allowing to alleviate hypoxia by continuously inhibiting CA activity and improving PDT of tumors. Findings show that subcutaneous HeLa tumors could be completely eradicated and no tumor recurred after irradiation with an 808 nm laser (0.33 W cm−2, 10 min). This pretargeted approach may be applied to enrich other therapeutic agents in tumors to improve targeted therapy.
A two‐step tumor‐pretargeted approach for multimodal imaging‐guided cancer theranostics via cascade alkaline phosphatase (ALP)‐mediated in situ self‐assembly and bioorthogonal inverse electron demand Diels–Alder (IEDDA) reaction enhances the accumulation of carbonic anhydrase inhibitors (SA‐Tz) and photosensitizers (775NP‐Tz) at the tumor site, efficiently alleviating hypoxic tumors and augmenting synergistic PDT efficacy in vivo.
Rational utilization of the rich light‐bio‐matter interplay taking place in single‐cell analysis represents a new technological direction in the field. The light‐fueled operation is expected to ...achieve advanced photoelectrochemical (PEC) single‐cell analysis with unknown possibilities. Here, a PEC nanoreactor capable of single‐cell sampling and near zero‐background Faradaic detection of intracellular microRNA (miR) is devised by the construction of a small reaction chamber accommodating the target‐triggered hybridization chain reaction for binding the metallointercalator of Ru(bpy)2(dppz)2+ as the signal reporter. Light stimulation of the dsDNA/metallointercalator adduct will induce the generation of photocurrents, underpinning a zero‐biased and near zero‐background PEC method toward Faradaic detection of non‐electrogenic miR at the single‐cell level. Using this nanotool, lower miR concentration in the near‐nucleus region than that in the main cytosol was revealed.
A photoelectrochemical nanoreactor was devised for single‐cell sampling and near zero‐background faradic detection of intracellular microRNA. This platform provided a new perspective for exploring light‐biomatter interplay toward single‐cell studies.
With reduced background and high sensitivity, photoelectrochemistry (PEC) may be applied as an intracellular nanotool and open a new technological direction of single‐cell study. Nevertheless, the ...present palette of single‐cell tools lacks such a PEC‐oriented solution. Here a dual‐functional photocathodic single‐cell nanotool capable of direct electroosmotic intracellular drug delivery and evaluation of oxidative stress is devised by engineering a target‐specific organic molecule/NiO/Ni film at the tip of a nanopipette. Specifically, the organic molecule probe serves simultaneously as the biorecognition element and sensitizer to synergize with p‐type NiO. Upon intracellular delivery at picoliter level, the oxidative stress effect will cause structural change of the organic probe, switching its optical absorption and altering the cathodic response. This work has revealed the potential of PEC single‐cell nanotool and extended the boundary of current single‐cell electroanalysis.
An integrated photocathodic nanotool was fabricated for dual‐functional intracellular drug delivery and evaluation of cellular oxidative stress in single live cell.
Two-photon excitation (TPE) nanoparticle-based photosensitizers (PSs) that combine the advantages of TPE and nanotechnology have emerged as attractive therapeutic agents for near-infrared red (NIR) ...light excited photodynamic therapy (PDT) for cancer treatment. TPE PDT is characterized by nonlinear absorption of two relatively low-energy photons of NIR light with the resulting emission of high-energy visible light. This high-energy light can sensitize oxygen to produce cytotoxic reactive oxygen species (ROS) and singlet oxygen (
O
) which can kill cancer cells. The long-wavelength light used to excite TPE NPs allows for deeper tissue penetration to achieve efficient PDT of deep-seated tumors. Moreover, TPE nanoparticles normally have large two-photon absorption (TPA) cross-sections, which hold great potential as efficient two-photon donors in PDT. In this review, we will summarize the recent advances made in the development of TPE nanoparticles for cancer PDT. Five different TPE nanoparticles, including quantum dots (QDs), carbon nanomaterials, silica nanoparticles, gold nanomaterials, and polymer nanoparticles, are summarized in detail, and the existing challenges as well as the future perspectives are also discussed.
Efficient water splitting through electrocatalysis holds great promise for producing hydrogen fuel in modern energy devices. Its real application however suffers from sluggish reaction kinetics due ...to the lack of high-performance catalysts except noble metals such as platinum. Herein, we report an active system of plasmonic-metal Au nanorods/molybdenum disulfide (MoS2) nanosheets hybrids for the hydrogen evolution reaction (HER). The plasmonic Au–MoS2 hybrids dramatically improve the HER, leading to a ∼3-fold increase of current under excitation of Au localized surface plasmon resonance (LSPR). A turnover of 8.76 s–1 at 300 mV overpotential is measured under LSPR excitation, which by far exceeds the activity of MoS2 catalysts reported recently. The HER enhancement can be largely attributed to the increase of carrier density in MoS2 induced by the injection of hot electrons of Au nanorods. We demonstrate that the synergistic effect of the hole scavengers can further facilitate electron–hole separation, resulting in a decrease of the overpotential of HER at MoS2 to ∼120 mV. This study highlights how metal LSPR activates the HER and promises novel opportunities for enhancing intrinsic activities of semiconducting materials.
Noble metal nanoparticles are promising catalysts in electrochemical reactions, while understanding the relationship between the structure and reactivity of the particles is important to achieve ...higher efficiency of electrocatalysis, and promote the development of single‐molecule electrochemistry. Electrogenerated chemiluminescence (ECL) was employed to image the catalytic oxidation of luminophore at single Au, Pt, and Au‐Pt Janus nanoparticles. Compared to the monometal nanoparticles, the Janus particle structure exhibited enhanced ECL intensity and stability, indicating better catalytic efficiency. On the basis of the experimental results and digital simulation, it was concluded that a concentration difference arose at the asymmetric bimetallic interface according to different heterogeneous electron‐transfer rate constants at Au and Pt. The fluid slip around the Janus particle enhanced local redox reactions and protected the particle surface from passivation.
Electrocatalytic oxidation of a luminophore at single Au, Pt, and Au‐Pt Janus nanoparticles was studied using electrogenerated chemiluminescence (ECL) microscopy. Compared to the monometal nanoparticles, the Janus particle structure exhibited enhanced ECL intensity and stability, indicating better catalytic efficiency.
Starvation therapy kills tumor cells via consuming glucose to cut off their energy supply. However, since glucose oxidase (GOx)‐mediated glycolysis is oxygen‐dependent, the cascade reaction based on ...GOx faces the challenge of a hypoxic tumor microenvironment. By decomposition of glycolysis production of H2O2 into O2, starvation therapy can be enhanced, but chemodynamic therapy is limited. Here, a close‐loop strategy for on demand H2O2 and O2 delivery, release, and recycling is proposed. The nanoreactor (metal‐protein‐polyphenol capsule) is designed by incorporating two native proteins, GOx and hemoglobin (Hb), in polyphenol networks with zeolitic imidazolate framework as sacrificial templates. Glycolysis occurs in the presence of GOx with O2 consumption and the produced H2O2 reacts with Hb to produce highly cytotoxic hydroxyl radicals (•OH) and methemoglobin (MHb) (Fenton reaction). Benefiting from the different oxygen carrying capacities of Hb and MHb, oxygen on Hb is rapidly released to supplement its consumption during glycolysis. Glycolysis and Fenton reactions are mutually reinforced by oxygen supply, consuming more glucose and producing more hydroxyl radicals and ultimately enhancing both starvation therapy and chemodynamic therapy. This cascade nanoreactor exhibits high efficiency for tumor suppression and provides an effective strategy for oxygen‐mediated synergistic starvation therapy and chemodynamic therapy.
A tandem nanoreactor that responds to intracellular adenosine triphosphate and glutathione is designed through introducing native protein, glucose oxidase, and hemoglobin, into protein‐polyphenol networks. The artificial enzyme can trigger glycolysis and Fenton reaction in tumor tissue. Simultaneous release of oxygen and free radicals reinforces tumor starvation and chemodynamic therapy.
New tools for single‐cell interrogation enable deeper understanding of cellular heterogeneity and associated cellular behaviors and functions. Information of RNA expression in single cell could ...contribute to our knowledge of the genetic regulatory circuits and molecular mechanism of disease development. Although significant progresses have been made for intracellular RNA analysis, existing methods have a trade‐off between operational complexity and practical feasibility. We address this challenge by combining the ionic current rectification property of nanopipette reactor with duplex‐specific nuclease‐assisted hybridization chain reaction for signal amplification to realize a simple and practical intracellular nanosensor with minimal invasiveness, which enables single‐cell collection and electrochemical detection of intracellular RNA with cell‐context preservation. Systematic studies on differentiation of oncogenic miR‐10b expression levels in non‐malignant breast cells, metastatic breast cancer cells as well as non‐metastatic breast cancer cells were then realized by this nanotool accompanied by assessment of different drugs effects. This work has unveiled the ability of electrochemistry to probe intracellular RNA and opened new opportunities to study the gene expression and heterogeneous complexity under physiological conditions down to single‐cell level.
A DSN‐assisted ICR‐nanopipette was fabricated for tracking the drug‐induced variation of the oncogenic miR‐10b expression levels of a dynamic manner. This method unveils the ability of electrochemistry to probe intracellular RNA and to study the gene expression and heterogeneous complexity under physiological conditions down to single‐cell level.
A dual-recognition carbon dot-based nanoprobe with controllable G-quadruplex release is developed for ratiometric fluorescence detection of pathogenic bacteria in a fast and precise way, which opens ...a promising avenue for efficient detection and early warning of pathogenic bacteria in food matrices.
A dual-recognition nanoprobe with controllable G-quadruplex release was developed for fast and precise ratiometric fluorescence detection of pathogenic bacteria.
