Crystal Structure, One-and Two-photon Excited Fluorescence and Bioimaging of a D-π-A Structural Triphenylamine Derivative

An electron donor-π-bridge-electron acceptor(D-π-A) optical functional organic compound comprising a triphenylamine moiety as the electron donor and pyridine moiety as the electron acceptor was synthesized. The structure of the compound was solved by single-crystal X-ray diffraction analysis. It crystallizes in monoclinic, space group P21, with a = 9.753(5), b = 8.815(5), c = 25.554(5) ?, β = 96.315(5)°, V = 2184(2) ?~3, Z = 2, D_c = 1.136 g/m^3, F(000) = 792, Μr = 746.92, μ = 0.069 mm^(-1), the final R = 0.0658 and wR = 0.1730 for 6790 observed reflections with I > 2(I). Study of nonlinear optical properties shows that the compound exhibits excellent two-photon excited fluorescence with the two-photon absorption cross-section value of 116 GM. The structure-property relationship was researched in detail through X-ray crystallography and quantum chemical calculation. Result of living cell imaging experiment shows its potential in fluorescence microscopy bioimaging.

Plasmonic nanoparticles and nucleic acids hybrids for targeted gene delivery,bioimaging,and molecular recognition

Promising biomedical applications of hybrid materials composed of gold nanoparticles and nucleic acids have attracted strong interest from the nanobiotechnological community.The particular interest is owing to the robust and easy-to-make synthetic approaches,to the versatile optical and catalytic properties of gold nanoparticles combined with the molecular recognition and programmable properties of nucleic acids.The significant progress is made in the develop-ment of DNA-gold nanostructures and their applications,such as molecular recognition,cell and tissue bioimaging,targeted delivery of therapeutic agents,etc.This review is focused on the critical discussion of the recent applications of the gold nanoparticles-nucleic acids hybrids.The effect of particle size,surface,charge and thermal properties on the interactions with functional nucleic acids is discussed.For each of the above topics,the basic principles,recent advances,and current challenges are discussed.Emphasis is placed on the systematization of data over the theranostic systems on the basis of the gold nanoparticles-nucleic acids hybrids.Specifically,we start our discussion with observation of the recent data on interaction of various gold nano-particles with nucleic acids.Further we describe existing gene delivery systems,nucleic acids detection,and bioimaging technologies.Finally,we describe the phenomenon of the polymerase chain reaction improvement by gold nanoparticle additives and its potential underlying mechanisms.Lastly,we provide a short summary of reported data and outline the challenges and perspectives.

Early diagnosis and bioimaging of lung adenocarcinoma cells/organs based on spectroscopy machine learning

Early diagnosis and fast detection with a high accuracy rate of lung cancer are important to improve the treatment effect.In this research,an early fast diagnosis and in vivo imaging method for lung adenocarcinoma are proposed by collecting the spectral data from normal and patients'cells/tissues,such as Fourier infrared spectroscopy(FTIR),UV-vis absorbance,and fluorescence spectra using anthocyanin.The FTIR spectra of human normal lung epithelial cells(BEAS-2B cells)and human lung adenocarcinoma cells(A549 cells)were collected.After the data is cleaned,a feature selection algorithm is used to select important wavelengths,and then,the classification models of support vector machine(SVM)and the grid search method are used to select the optimal model parameters(accuracy:96.89%on the training set and 88.57%on the test set).The optimal model is used to classify all samples,and the accuracy is 94.37%.Moreover,the anthocyanin was prepared and used for the intracellular absorbance and fluorescence,and the optimized algorithm was used for classification(accuracy:91.38%on the training set and 80.77%on the test set).Most importantly,the in vivo cancer imaging can be performed using anthocyanin.The results show that there are differences between lung ade-nocarcinoma and normal lung tissues at the molecular level,reflecting the accuracy,intui-tiveness,and feasibility of this algorithm-assistant anthocyanin imaging in lung cancer diagnosis,thus showing the potential to become an accurate and effective technical means for basic research and clinical diagnosis.

The role of surface functionalization of silica nanoparticles for bioimaging

Among the several types of inorganic nanoparticles available,silica nanoparticles(SNP)have earned their relevance in biological applications namely,as bioimaging agents.In fact,uorescent SNP(FSNP)have been explored in this-eld as protective nanocarriers,overcoming some limitations presented by conventional organic dyes such as high photobleaching rates.A crucial aspect on the use of uorescent SNP relates to their surface properties,since it determines the extent of interaction between nanoparticles and biological systems,namely in terms of colloidal stability in water,cellular recognition and internalization,tracking,biodistribution and speci-city,among others.Therefore,it is imperative to understand the mechanisms underlying the interaction between biosystems and the SNP surfaces,making surface functionalization a relevant step in order to take full advantage of particle properties.The versatility of the surface chemistry on silica platforms,together with the intrinsic hydrophilicity and biocompatibility,make these systems suitable for bioimaging applications,such as those mentioned in this review.

Conjugated 8-Hydroxylquinoline-Based Fluorescent Chemosensor for Zn^(2+) and Cd^(2+) and Bioimaging Application in Living Cells

A conjugated 8-hydroxyquinoline( 8-HQ)-based fluorescent chemosensor( 1) for Zinc ion( Zn^(2+)) and Cadmium ion( Cd^(2+)) was developed in aqueous solution and used for Zinc ion living cells bioimaging. The probe 1 was weakly fluorescent,but displayed a strong fluorescence at 580 nm with a large Stokes shift of150 nm in the presence of Zn^(2+) or Cd^(2+). This probe allows the detections of Zn^(2+) in the range of 0. 8-10 μmol/L and Cd^(2+) in the range of 0. 8-8 μmol/L,with the limit of detections of 0. 2 and 0. 6μmol/L for Zn^(2+) and Cd^(2+),respectively. The present probe was successfully used for fluorescence bioimaging of Zn^(2+) or Cd^(2+) in the living cells.

Hybridization chain reaction-based DNA nanomaterials for biosensing,bioimaging and therapeutics

DNA nanomaterials hold great promise in biomedical fields due to its excellent sequence programmability,molecular recognition ability and biocompatibility.Hybridization chain reaction(HCR)is a simple and efficient isothermal enzyme-free amplification strategy of DNA,generating nicked double helices with repeated units.Through the design of HCR hairpins,multiple nanomaterials with desired functions are assembled by DNA,exhibiting great potential in biomedical applications.Herein,the recent progress of HCR-based DNA nanomaterials for biosensing,bioimaging and therapeutics are summarized.Representative works are exemplified to demonstrate how HCR-based DNA nanomaterials are designed and constructed.The challenges and prospects of the development of HCR-based DNA nanomaterials are discussed.We envision that rationally designing HCR-based DNA nanomaterials will facilitate the development of biomedical applications.

Electrostatic interaction-mediated 1:1 complexes for high-contrast mitochondrial-targeted phosphorescence bioimaging

Organelle-targeted imaging can provide information on cellular functions and intracellular interactions,being significant for disease diagnosis.The use of room-temperature phosphorescence(RTP)in organelle-targeted imaging can fully utilize its unique characteristics of long wavelength and deep penetration.However,this technology has long been plagued by insufficient probe targeting and limited luminous intensity.In this work,we prepared a series of complexes composed of multicationic persulfurated arenes and biomacromolecules via electrostatic interactions in 1:1 stoichiometry for high-contrast mitochondrial-targeted RTP imaging.Such an electrostatic interaction design effectively prevented the self-aggregation of the probes,which is not conducive to mitochondrial targeting.Simultaneously,it suppressed the non-radiative decay to the maximum extent,enabling the probes to exhibit strong RTP signals both in aqueous solution and at the cellular level.Furthermore,the biomacromolecules can serve as carriers for an electrostatic interaction transfer of the persulfurated arenes to mitochondria.This leads to high mitochondrial targeting Pearson's correlation coefficients of the probes and high-contrast RTP imaging effects,as well as the independence of the co-incubated probe concentration.These results provide new insights for the development of targeted imaging technologies.

Waterproof Perovskite Quantum Dots for In-vivo Photoluminescence Bioimaging

Perovskite quantum dots(PQDs)have demonstrated great promise in bioimaging applications owing to their outstanding photophysical properties.Nonetheless,their practicality is seriously limited by the instability of PQDs against moisture.Here we develop a post-synthetic ligand exchange strategy to construct silica-coated PQD(PQD@SiO_(2))nanocrystals,which results in the simultaneous improvement of photoluminescence efficiency and moisture stability.More importantly,compared to the classical in-situ ligand exchange method of fabricating PQD@SiO_(2),the issues of chemical etching and resultant photoluminescence degradation are judiciously overcome.Employing the proposed PQD@SiO_(2),we showcase their robust usefulness in labeling chlorella,paving the way for PQD-based in-vivo photoluminescence bioimaging methodology.

A non-peptide-based chymotrypsin-targeted long-wavelength emission fluorescent probe with large Stokes shift and its application in bioimaging

As a hydrolase,chymotrypsin(CHT)is involved in many physiological activities,and its abnormal activity is closely related to diabetes,pancreatic fibrosis,chronic pancreatitis and pancreatic cancer.In this work,an innovative long-wavelength emission fluorescent probe TCF-CHT was designed and synthesized for the high specificity detection of CHT,which utilized TCF-OH and a mimetic peptide substrate 4-bromobutyryl as chromogenic group and recognition group,respectively.TCF-CHT exhibited excellent selectivity and eye-catching sensitivity(8.91 ng/m L)towards CHT,“off-on”long-wavelength emission at 670 nm and large Stokes shift(140 nm).Furthermore,the successful fulfillment and perfect performance in imaging endogenous CHT in complex organisms(P815 cells,HepG2 cells,zebrafish and tumor-bearing mice)verified its potential as a powerful tool for the recognition of CHT in complicated biological environments.

Organic Host-Guest Materials with Bright Red Room-Temperature Phosphorescence for Persistent Bioimaging

Organic room-temperature phosphorescence(RTP)materials have attracted immense attention in bioimaging due to their long emission lifetime and large Stokes shift.RTP materials with long emission wavelength can improve the penetration depth for bioimaging.However,the design of red persistent RTP materials is still challenging.In this study,a fused-ring structure has been proposed to effectively decrease the triplet energy level,thus extending the emission wavelength of phosphorescence.In addition,the fused-ring structure exhibits a high molar extinction coefficient(ɛ)and high luminescence efficiency due to the rigid structure.A new class of crystalline hosts(iminodibenzyl,IDB)are developed to stabilize the triplet excitons that are generated from the fused-ring molecules.The maximum RTP wavelength of doping materials can reach 635 nm with a lifetime of 9.35 ms.Water-disperse nanoparticles are successfully prepared for in vivo time-resolved bioimaging,which eliminates the background fluorescence interference from biological tissues.These reveal a delicate design strategy for the construction of long-wavelength emissive RTP materials for high-resolution bioimaging.

Emerging NIR-Ⅱ Luminescent Gold Nanoclusters for In Vivo Bioimaging

Gold nanoclusters(AuNCs)with near-infraredⅡ(NIR-Ⅱ)photoluminescence(PL)have emerged as novel bioimaging probes for in vivo disease diagnosis.So far,it still lacks a systematic review focusing on the synthesis,PL tuning,and in vivo imaging of NIR-Ⅱluminescent AuNCs.In this review,we briefly introduce the synthesis of NIR-Ⅱluminescent AuNCs using various surface ligands.We discuss the origins and properties of NIR-ⅡPL in AuNCs,and summarize the strategies for improving and/or tuning NIR-ⅡPL emissions.We also provide an overview of the recent progress in the application of AuNCs in tumor-targeted imaging,molecular imaging,and other areas(such as the sensitive imaging of bones,vessels,lymph nodes,etc.).Finally,we present the prospects and challenges in the field of NIR-Ⅱluminescent AuNCs and related imaging applications,expecting to offer comprehensive understanding of this field,and thereby deepening and broadening the biological application of AuNCs.

Tetrapeptide self-assembled multicolor fluorescent nanoparticles for bioimaging applications

The biocompatibility and biodegradability of peptide self-assembled materials makes them suitable for many biological applications,such as targeted drug delivery,bioimaging,and tracking of therapeutic agents.According to our previous research,self-assembled fluorescent peptide nanoparticles can overcome the intrinsic optical properties of peptides.However,monochromatic fluorescent nanomaterials have many limitations as luminescent agents in biomedical applications.Therefore,combining different fluorescent species into one nanostructure to prepare fluorescent nanoparticles with multiple emission wavelengths has become a very attractive research area in the bioimaging field.In this study,the tetrapeptide Trp-Trp-Trp-Trp(WWWW)was self-assembled into multicolor fluorescent nanoparticles(TPNPs).The results have demonstrated that TPNPs have the blue,green,red and near infrared(NIR)fluorescence emission wavelength.Moreover,TPNPs have shown excellent performance in multicolor bioimaging,biocompatibility,and photostability.The facile preparation and multicolor fluorescence features make TPNPs potentially useful in multiplex bioanalysis and diagnostics.

How temperature and hydrostatic pressure impact organic room temperature phosphorescence from H-aggregation of planar triarylboranes and the application in bioimaging

Highly efficient persistent organic room temperature phosphorescence(RTP) has attracted increasing attention because of promising applications in fields of chemical sensors, optoelectronic devices, information security, and bioimaging, etc. Wherein,the crystal engineering of H-aggregation offers stabilization for long-lived triplet exciton for RTP, but the related research is rare because of the scarcity of ideal phosphorescent H-aggregate. Herein, we designed planar tricoordinate organoboron derivatives with molecular arrangement in ideal H-aggregation. The integration of Br atom can largely enhance RTP efficiency through increasing SOC effect, while the antiparallel molecular arrangement causes annihilation of triplet exciton. Thanks to good selfassembly property, their RTP can even be observed in PMMA matrix with doping ratio of merely 1 wt%. We further found that the cryogenic temperature contributes to stabilizing triplet exciton in H-aggregation, leading to red-shifted phosphorescence. By applying high hydrostatic pressure, the phosphorescence was largely enhanced and redshifted, demonstrating the crucial role of H-aggregation on RTP property. In phosphorescent tissue imaging of live mouse, nanoparticles of BrBA exhibited high contrast image via eliminating the interference of autofluorescence.

Recent Advances in Triplet-Triplet Annihilation Upconversion for Bioimaging and Biosensing

Photon upconversion is an anti-Stokes process that converts low-energy photons into high-energy photons.The use of upconversion luminescence can avoid the autofluorescence of biological tissue and realize background-free bioimaging with a high signal-to-noise ratio at a low power density.In addition,the excitation of red or near-infrared light facilitates the reduction of photodamage in biological tissues and subsequent bioimaging of deep tissue features in vivo.Meanwhile,upconversion emission-mediated bio sensing offers both high sensitivity and low detection limits for quantitative analysis of the target substances in complicated biological samples.Due to its high upconversion quantum yield,low excitation power density,and tunable absorption and emission wavelengths,triplet-triplet annihilation upconversion(TTA-UC)has garnered considerable interest for bioimaging and biosensing.This review will introduce the fundamental concepts of TTA-UC,the factors that influence TTA-UC materials,and the methodologies for preparing TTA-UC materials.The important progress of TTA-UC in bioimaging and bio sensing in recent years will also be discussed in detail in vitro and in vivo.Furthermore,the current challenges of TTA-UC in bioimaging and biosensing will be discussed,along with potential solutions.

Near-infrared fluorophores with absolute aggregation-caused quenching and negligible fluorescence re-illumination for in vivo bioimaging of nanocarriers

Environment-responsive fluorophores with aggregation-caused quenching(ACQ)properties have been applied to track nanocarriers with reduced artefacts caused by unbound or free fluorophores but suffer from incomplete fluorescence quenching and significant re-illumination,which undermine bioimaging accuracy.Herein,through structural modifications to reinforce the hydrophobicity,planarity and rigidity of fluorophores with an aza-BODIPY framework,probes featuring absolute ACQ(aACQ)and negligible re-illumination are developed and evaluated in various nanocarriers.aACQ probes,FD-B21 and FD-C7,exhibit near-infrared emission,high quantum yield,photostability,water sensitivity,and negligible re-illumination in blood,plasma and 1%Tween-80 in contrast to ACQ probe P2 and conventional probe DiR.All nanocarriers can be labeled efficiently by the tested fluorophores.Polymeric micelles(PMs)labeled by different aACQ probes manifest similar biodistribution patterns,which however differ from that of DiR-labeled PMs and could be ascribed to the appreciable re-illumination of DiR.Significantly lower re-illumination is also found in aACQ probes(2%-3%)than DiR(20%-40%)in Caco-2,Hela,and Raw264.7 cells.Molecular dynamics simulations unravel the molecular mechanisms behind aggregation and re-illumination,supporting the hypothesis of planarity dependency.It is concluded that aACQ fluorophores demonstrate excellent water sensitivity and negligible fluorescence re-illumination,making themselves useful tools for more accurate bioimaging of nanocarriers.

Engineering CRISPR/Cas-based nanosystems for therapeutics, diagnosis and bioimaging

CRISPR/Cas system has been utilized to rationally manipulate intracellular genes,and it has been engineered as versatile and efficient gene editing tools with precise site-specificity and excellent targeting ability for therapeutics,diagnostics,and bioimaging.Here,the evolution and application of CRISPR/Cas systems were sketched chronologically.Landmark works were exemplified to illustrate the design principles of CRISPR/Cas systems.Furthermore,the delivery vectors of CRISPR/Cas system especially DNA nanomaterials-based vectors were categorized and illuminated.DNA nanomaterials are suitable for CRISPR/Cas system delivery via base pairing due to its sequence programmability and biocompatibility.Then the applications of CRISPR/Cas in diagnosis and genomic imaging were highlighted.At the end of the review,the challenges and opportunities of CRISPR/Cas systems were deeply discussed.We envision that the grant advances on CRISPR/Cas systems will promote the development of interdisciplinary fields in chemistry,biology and medicine.

Endogenous formaldehyde responsive fluorescent probe for bioimaging

Formaldehyde(FA),as the simplest endogenous carbonyl molecule,participates in many biosynthesis and metabolism in living organisms,such as nucleotides and adenosine triphosphate(ATP).FA concentrations are sub-millimolar in the normal healthy body,but can rise significantly in a number of disease pathologies.As a result,detecting endogenous FA is critical for illness diagnosis and rehabilitation therapy monitoring.Recent studies have focused on the FA-responsive turn-on fluorescence probe,which has huge promise in the detection and visualization of FA in living cells and organisms,as well as exceptional use in disease diagnosis and therapeutic monitoring.This review summarizes the fluorescence luminescence mechanism and design concepts of FA fluorescent probes,as well as their recent applications in bioimaging and illness diagnostics.Additionally,this article indicates the present dilemma of FA-responsive fluorescent probe,including selectivity,specificity,and detection mode,which may provide references for the development of FA-responsive fluorescent probes.

Biological Interaction and Imaging of Ultrasmall Gold Nanoparticles

Ultrasmall gold nanoparticles(AuNPs)typically includes atomically precise gold nanoclusters(AuNCs)and AuNPs with a core size below 3 nm.Serving as a bridge between small molecules and traditional inorganic nanoparticles,the ultrasmall AuNPs show the unique advantages of both small molecules(e.g.,rapid distribution,renal clearance,low non-specific organ accumulation)and nanoparticles(e.g.,long blood circulation and enhanced permeability and retention effect).The emergence of ultrasmall AuNPs creates significant opportunities to address many challenges in the health field including disease diagnosis,monitoring and treatment.Since the nano–bio interaction dictates the overall biological applications of the ultrasmall AuNPs,this review elucidates the recent advances in the biological interactions and imaging of ultrasmall AuNPs.We begin with the introduction of the factors that influence the cellular interactions of ultrasmall AuNPs.We then discuss the organ interactions,especially focus on the interactions of the liver and kidneys.We further present the recent advances in the tumor interactions of ultrasmall AuNPs.In addition,the imaging performance of the ultrasmall AuNPs is summarized and discussed.Finally,we summarize this review and provide some perspective on the future research direction of the ultrasmall AuNPs,aiming to accelerate their clinical translation.

Dopant-Controlled Synthesis of Water-Soluble Hexagonal NaYF_(4) Nanorods with Efficient Upconversion Fluorescence for Multicolor Bioimaging

A novel strategy is proposed to directly synthesize water-soluble hexagonal NaYF4 nanorods by doping rare-earth ions with large ionic radius (such as La^(3+), Ce^(3+), Pr^(3+), Nd^(3+), Sm^(3+), Eu^(3+), and Gd^(3+)), and the dopant- controlled growth mechanism is studied. Based on the doping effect, we fabricated water-soluble hexagonal NaYF4:(Yb,Er)/La and NaYF4:(Yb,Er)/Ce nanorods, which exhibited much brighter upconversion fluorescence than the corresponding cubic forms. The sizes of the nanorods can be adjusted over a broad range by changing the dopant concentration and reaction time. Furthermore, we successfully demonstrated a novel depth-sensitive multicolor bioimaging for in vivo use by employing the as-synthesized NaYF4:(Yb,Er)/La nanorods as probes.

Recent progress in engineering near-infrared persistent luminescence nanoprobes for time-resolved biosensing/bioimaging

Persistent luminescence nanoprobes (PLNPs) can remain luminescent after ceasing excitation.Due to the ultra-long decay time of persistent luminescence (PersL),autofluorescence interference can be efficiently eliminated by collecting PersL signal after autofluorescence decays completely,thus the imaging contrast and sensing sensitivity can be significantly improved.Since near-infrared (NIR) light shows reduced scattering and absorption coefficient in penetrating biological organs or tissues,near-infrared persistent luminescence nanoprobes (NIR PLNPs) possess deep tissue penetration and offer a bright prospect in the areas of in vivo biosensing/bioimaging.In this review,we firstly summarize the design of different types of NIR PLNPs for biosensing/bioimaging,such as transition metal ions-doped NIR PLNPs,lanthanide ions-doped NIR PLNPs,organic molecules-based NIR PLNPs,and semiconducting polymer self-assembled NIR PLNPs.Notably,organic molecules-based NIR PLNPs and semiconductor self-assembled NIR PLNPs,for the first time,were introduced to the review of PLNPs.Secondly,the effects of different types of charge carriers on NIR PersL and luminescence decay of NIR PLNPs are significantly emphasized so as to build up an in-depth understanding of their luminescence mechanism.It includes the regulation of valence band and conduction band of different host materials,alteration of defect types,depth and concentration changes caused by ion doping,effective radiation transitions and energy transfer generated by different luminescence centers.Given the design and potential of NIR PLNPs as long-lived luminescent materials,the current challenges and future perspective in this rapidly growing field are also discussed.