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. Herein, recent research progress on the design and construction of light‐activated nanoprobes to improve bioimaging and sensing performance in complex biological systems is introduced. First, recent innovative strategies and their underlying mechanisms for light‐controlled imaging are reviewed, including photoswitchable nanoprobes and phototargeted nanosystems. Subsequently, a short highlight is provided on the development of light‐activatable nanoprobes for biosensing, which offer possibilities for the remote control of biorecognition and sensing activity in a precise manner both temporally and spatially. Finally, perspectives and challenges in light‐activated nanoprobes are commented.     

Tunable Fabrication of Molybdenum Disulfide Quantum Dots for Intracellular MicroRNA Detection and Multiphoton Bioimaging

Molybdenum disulfide (MoS₂) quantum dots (QDs) (size <10 nm) possess attractive new properties due to the quantum confinement and edge effects as graphene QDs. However, the synthesis and application of MoS₂ QDs has not been investigated in great detail. Here, a facile and efficient approach for synthesis of controllable‐size MoS₂ QDs with excellent photoluminescence (PL) by using a sulfuric acid‐assisted ultrasonic route is developed for this investigation. Various MoS₂ structures including monolayer MoS₂ flake, nanoporous MoS₂, and MoS₂ QDs can be yielded by simply controlling the ultrasonic durations. Comprehensive microscopic and spectroscopic tools demonstrate that the MoS₂ QDs have uniform lateral size and possess excellent excitation‐independent blue PL. The as‐generated MoS₂ QDs show high quantum yield of 9.65%, long fluorescence lifetime of 4.66 ns, and good fluorescent stability over broad pH values from 4 to 10. Given the good intrinsic optical properties and large surface area combined with excellent physiological stability and biocompatibility, a MoS₂ QDs‐based intracellular microRNA imaging analysis system is successfully constructed. Importantly, the MoS₂ QDs show good performance as multiphoton bioimaging labeling. The proposed synthesis strategy paves a new way for facile and efficient preparing MoS₂ QDs with tunable‐size for biomedical imaging and optoelectronic devices application.     

A MoS2/PTCDA Hybrid Heterojunction Synapse with Efficient Photoelectric Dual Modulation and Versatility

Just as biological synapses provide basic functions for the nervous system, artificial synaptic devices serve as the fundamental building blocks of neuromorphic networks; thus, developing novel artificial synapses is essential for neuromorphic computing. By exploiting the band alignment between 2D inorganic and organic semiconductors, the first multi‐functional synaptic transistor based on a molybdenum disulfide (MoS₂)/perylene‐3,4,9,10‐tetracarboxylic dianhydride (PTCDA) hybrid heterojunction, with remarkable short‐term plasticity (STP) and long‐term plasticity (LTP), is reported. Owing to the elaborate design of the energy band structure, both robust electrical and optical modulation are achieved through carriers transfer at the interface of the heterostructure, which is still a challenging task to this day. In electrical modulation, synaptic inhibition and excitation can be achieved simultaneously in the same device by gate voltage tuning. Notably, a minimum inhibition of 3% and maximum facilitation of 500% can be obtained by increasing the electrical number, and the response to different frequency signals indicates a dynamic filtering characteristic. It exhibits flexible tunability of both STP and LTP and synaptic weight changes of up to 60, far superior to previous work in optical modulation. The fully 2D MoS₂/PTCDA hybrid heterojunction artificial synapse opens up a whole new path for the urgent need for neuromorphic computation devices.     

Cross‐Linkable and Dual Functional Hybrid Polymeric Electron Transporting Layer for High‐Performance Inverted Polymer Solar Cells

A cross‐linkable dual functional polymer hybrid electron transport layer (ETL) is developed by simply adding an amino‐functionalized polymer dopant (PN4N) and a light crosslinker into a commercialized n‐type semiconductor (N2200) matrix. It is found that the resulting hybrid ETL not only has a good solvent resistance, facilitating multilayers device fabrication but also exhibits much improved electron transporting/extraction properties due to the doping between PN4N and N2200. As a result, by using PTB7‐Th:PC₇₁BM blend as an active layer, the inverted device based on the hybrid ETL can yield a prominent power conversion efficiency of around 10.07%. More interestingly, photovoltaic property studies of bilayer devices suggest that the absorption of the hybrid ETL contributes to photocurrent and hence the hybrid ETL simultaneously acts as both cathode interlayer material and an electron acceptor. The resulting inverted polymer solar cells function like a novel device architectures with a combination of a bulk heterojunction device and miniature bilayer devices. This work provides new insights on function of ETLs and may be open up a new direction for the design of new ETL materials and novel device architectures to further improve device performance.     

A High-Performance Hybrid Biofuel Cell with a Honeycomb-Like Ti3C2Tx/MWCNT/AuNP Bioanode and a ZnCo2@NCNT Cathode for Self-Powered Biosensing

This work focusses on developing a hybrid enzyme biofuel cell-based self-powered biosensor with appreciable stability and durability using murine leukemia fusion gene fragments (tDNA) as a model analyte. The cell consists of a Ti₃C₂T_x/multiwalled carbon nanotube/gold nanoparticle/glucose oxidase bioanode and a Zn/Co-modified carbon nanotube cathode. The bioanode uniquely exhibits strong electron transfer ability and a high surface area for the loading of 1.14 × 10⁻⁹ mol cm⁻² glucose oxidase to catalyze glucose oxidation. Meanwhile, the abiotic cathode with a high oxygen reduction reaction activity negates the use of conventional bioenzymes as catalysts, which aids in extending the stability and durability of the sensing system. The biosensor offers a 0.1 fm –1 nm linear range and a detection limit of 0.022 fm tDNA. Additionally, the biosensor demonstrates a reproducibility of ≈4.85% and retains ≈87.42% of the initial maximal power density after a 4-week storage at 4 °C, verifying a significantly improved long-term stability.     

Intrinsic 3D Prestressing: A New Route for Increasing Strength and Improving Toughness of Hybrid Inorganic Biocements

Cement is the most consumed resource and is the most widely used material globally. The ability to extrinsically prestress cementitious materials with tendons usually made from steel allows the creation of high‐strength bridges and floors from this otherwise brittle material. Here, a dual setting cement system based on the combination of hydraulic cement powder with an aqueous silk fibroin solution that intrinsically generates a 3D prestressing during setting, dramatically toughening the cement to the point it can be cut with scissors, is reported. Changes of both ionic concentration and pH during cement setting are shown to create an interpenetrating silk fibroin inorganic composite with the combined properties of the elastic polymer and the rigid cement. These hybrid cements are self‐densifying and show typical ductile fracture behavior when dry and a high elasticity under wet conditions with mechanical properties (bending and compressive strength) nearly an order of magnitude higher than the fibroin‐free cement reference.     

Traceable Bioinspired Nanoparticle for the Treatment of Metastatic Breast Cancer via NIR‐Trigged Intracellular Delivery of Methylene Blue and Cisplatin

Cytotoxic T lymphocyte (CTL) eliminates abnormal cells through target recognition‐triggered intracellular toxin delivery. Chimeric antigen receptor T‐cell improves cancer cell recognition of CTL, but its effectiveness and safety in solid tumor treatment are still hampered by poor tumor infiltration, suppressive tumor microenvironment, and severe on‐target off‐tumor toxicity. Given the functionality and challenges of CTL in cancer therapy, herein, a CTL‐inspired nanovesicle (MPV) with a cell membrane–derived shell and a methylene blue (MB) and cisplatin (Pt) loaded gelatin nanogel core is created. The MPV generates contrast for tumor photoacoustic imaging, and produces hyperthermia upon laser irradiation, enabling photothermal imaging and deep tumor penetration. Meanwhile, it releases MB and Pt, and then delivers them into the cytosol of cancer cells, which process can be visualized by imaging the recovery of MB‐derived fluorescence. The localized hyperthermia, photodynamic therapy, and chemotherapy together kill 4T1 breast cancer cells effectively, resulting in primary tumor regression and 97% inhibition of pulmonary metastasis, without significant toxicity to the animals. Taken together, the MPV shows tumor‐specific and stimuli‐triggered intracellular toxin delivery with advantages in traceable accumulation and activation, high tumor penetration, and triple combination therapy, and thus can be an effective nanomedicine for combating metastatic breast cancer.     

Hybrid Protein Nano‐Reactors Enable Simultaneous Increments of Tumor Oxygenation and Iodine‐131 Delivery for Enhanced Radionuclide Therapy

It is hard for current radionuclide therapy to render solid tumors desirable therapeutic efficacy owing to insufficient tumor‐targeted delivery of radionuclides and severe tumor hypoxia. In this study, a biocompatible hybrid protein nanoreactor composed of human serum albumin (HSA) and catalase (CAT) molecules is constructed via glutaraldehyde‐mediated crosslinking. The obtained HSA‐CAT nanoreactors (NRs) show retained and well‐protected enzyme stability in catalyzing the decomposition of H₂O₂ and enable efficient labeling of therapeutic radionuclide iodine‐131 (¹³¹I). Then, it is uncovered that such HSA‐CAT NRs after being intravenously injected into tumor‐bearing mice exhibit efficient passive tumor accumulation as vividly visualized under the fluorescence imaging system and gamma camera. As the result, such HSA‐CAT NRs upon tumor accumulation would significantly attenuate tumor hypoxia by decomposing endogenous H₂O₂ produced by cancer cells to molecular oxygen, and thereby remarkably improve the therapeutic efficacy of radionuclide ¹³¹I. This study highlights the concise preparation of biocompatible protein nanoreactors with efficient tumor homing and hypoxia attenuation capacities, thus enabling greatly improved tumor radionuclide therapy with promising potential for future clinical translation.     

Dual Intratumoral Redox/Enzyme‐Responsive NO‐Releasing Nanomedicine for the Specific,High‐Efficacy,and Low‐Toxic Cancer Therapy

Chemotherapy suffers numbers of limitations including poor drug solubility, nonspecific biodistribution, and inevitable adverse effects on normal tissues. Tumor‐targeted delivery and intratumoral stimuli‐responsive release of drugs by nanomedicines are considered to be highly promising in solving these problems. Compared with traditional chemotherapeutic drugs, high concentration of nitric oxide (NO) exhibits unique anticancer effects. The development of tumor‐targeting and intratumoral microenvironment‐responsive NO‐releasing nanomedicines is highly desired. Here a novel kind of organic–inorganic composite nanomedicine (QM‐NPQ@PDHNs) is presented by encapsulating a glutathione S‐transferases π (GSTπ)‐responsive drug O²‐(2,4‐dinitro‐5‐{[2‐(β‐d ‐galactopyranosyl olean‐12‐en‐28‐oate‐3‐yl)‐oxy‐2‐oxoethyl] piperazine‐1‐yl} phenyl) 1‐(methylethanolamino)diazen‐1‐ium‐1,2‐dilate (NPQ) as NO donor and an aggregation‐induced‐emission (AIE) red fluorogen QM‐2 into the cores of the hybrid nanomicelles (PEGylated disulfide‐doped hybrid nanocarriers (PDHNs)) with glutathione (GSH)‐responsive shells. The QM‐NPQ@PDHN nanomedicine is able to respond to the intratumoral over‐expressed GSH and GSTπ, resulting in the responsive biodegradation of the protective organosilica shell and NPQ release, and subsequent NO release within the tumor, respectively, and thus normal organs remain unaffected. This work demonstrates a paradigm of dual intratumoral redox/enzyme‐responsive NO‐release nanomedicine for tumor‐specific and high‐efficacy cancer therapy.     

Design of a Molecular Hybrid of Dual Peptide Inhibitors Coupled on AuNPs for Enhanced Inhibition of Amyloid β‐Protein Aggregation and Cytotoxicity

Aggregation of amyloid‐β protein (Aβ) is a pathological hallmark of Alzheimer's disease (AD), so the inhibition of Aβ aggregation is an important strategy for the prevention and treatment of AD. Herein, we proposed to design molecular hybrids of peptide inhibitors by combining two peptide inhibitors, VVIA and LPFFD, into single sequences and examined their effects on Aβ₄₂ aggregation and cytotoxicity. The hybrid peptides exhibit increased but moderate inhibitory activity as compared to their two precursors. By conjugating the peptides onto gold nanoparticles (AuNPs), however, the inhibition activity of the corresponding peptide@AuNPs against Aβ₄₂ aggregation and cytotoxicity is greatly improved. Among them, VVIACLPFFD (VCD10)@AuNP is the most effective, which increases cell viability from 48% to 82% at a dosage as low as 0.1 nmol L^?1 (NPs) or 40 nmol L^?1 (peptide). The superior capacity of VCD10@AuNPs is considered due to its branched dual‐inhibitor sequence, and its special surface orientation and conformation. These structural features promote its synergetic interactions with Aβ on AuNP surface, leading to strong inhibitions of Aβ oligomerization and fibrillation and the cytotoxicity caused by the aggregation species. The findings suggest that potent inhibitors can be derived by hybridization of multiple peptide inhibitors with the hybrid products coupled onto nanoparticles.