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.

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.

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.

Recent progress on eco-friendly quantum dots for bioimaging and diagnostics

Semiconductor quantum dots(QDs),as promising fluorescent materials,have been widely applied in biomedical application due to their unique optical properties.Currently,the most intensively studied are Cd-containing QDs(Cd-based QDs),whose potential toxicity prevents their further commercialization.In recent years,the eco-friendly QDs with low toxicity and environmental friendliness have begun to be developed,showing great potential in biomedical applications.The high-quality synthesis of eco-friendly QDs and the appropriate surface modification are key to realize their applications.This review summarizes the progress of eco-friendly QDs for biomedical applications,including their designed preparation,optical properties,surface modification,toxicity,and their applications in bioimaging and diagnostics.Finally,the challenges of eco-friendly QDs for future bioimaging and diagnostics application were provided.We believe this review will provide important guidance for promoting the development of eco-friendly QDs in bioimaging and diagnostics.

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.

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.

Kilogram-scale synthesis of carbon quantum dots for hydrogen evolution, sensing and bioimaging

The development of large-scale synthetic methods for high quality carbon quantum dots(CQDs) is fundamental to their applications.However,the macroscopic preparation and scale up synthetic of CQDs is still in its infancy.Here,we report a facile,green,kilogram-scale synthesis of high quality fluorescent CQDs derived from poplar leaves via a one-step hydrothermal method.Notably,the throughput of CQDs can reach a level up to as high as 1.4975 kg in one pot.The structure and properties of the as-prepared CQDs were assessed through TEM,XRD,XPS and various spectroscopic methods.The obtained high quality CQD s with a photoluminescent quantum yield of 10.64% showed remarkable stability in aqueous media,rich functional groups,high photostability,consistent photoluminescence within biological pH range and low cytotoxicity.On account of these good properties,we demonstrated the multifunctional application to electrocatalytic water splitting,Fe^3+ sensing and bioimaging.It showed remarkable electrocatalytic activity,Fe^3+ sensitivity and good biocompatibility.This study provides a green,facile,inexpensive and large-scale method for producing high quality CQDs,which provides application value for large-scale production of CQDs.

Metal-Organic Frameworks-Based Fluorescent Nanocomposites for Bioimaging in Living Cells and in vivo

Metal-organic frameworks(MOFs)as a class of porous functional materials have attracted more and more attention for biomedical applications.To date,MOFs have been developed for bioimaging based on a series of advantages such as the large surface areas,high porosity,fluorescence functionalities and good biocompatibility.It is worth noting that organic or inorganic fluorescent materials such as fluorescent dyes,quantum dots,metal nanoclusters and nanosheets can combine MOFs or be encapsulated in MOFs to form fluorescent nanocomposites for excellent imaging function.Importantly,excellent imaging capabilities are of great significance in living cells and in vivo for detection,diagnosis and cancer therapy.In this review,we focus on the recent research of the bioimaging in living cells and in vivo based on various MOF-based nanocomposites and their potential biological clinical applications.

Recent advances in autofluorescence-free biosensing and bioimaging based on persistent luminescence nanoparticles

Persistent luminescence nanoparticles (PLNPs) are a series of emerging luminescent nanomaterials which can emit persistently after ceasing the external excitation. Due to the long decay time of persistent luminescence, the background autofluorescence in complex sample and tissues can be effectively eliminated, thus significantly improving the sensitivity of bioanalysis. Besides, such a long decay time of luminescence also makes PLNPs valuable for long-term bioimaging. Benefiting from these merits, PLNPs have been widely used for biomedical applications, especially biosensing and bioimaging. In this review,we conclude the progress in the application of PLNPs at biosensing and bioimaging in recent years, and also provide our understanding of the prospects.

Surface Modified Persistent Luminescence Probes for Biosensing and Bioimaging:A Review

Persistent luminescence materials(PLMs)are a class of unique luminescent materials that can remain luminescent for a few milliseconds to days without constant excitation.By virtue of the super long decay time,PLMs have been extensively explored in biosensing and bioimaging applications to elimin ate autofluorescence interference and improve signal-to-noise ratio in complex samples and tissues.However,nude PLMs often suffer from the poor stability,selectivity,and biocompatibility in biological system and in vivo,which greatly impedes their applications in biomedicine and bioanalysis.Remarkably,surface modification is a viable solution that endows PLMs with span-new features and can make PLMs suitable for organisms by altering PLMs’interaction with biological system.In this review,commonly used strategies for surface modification of PLMs are briefly introduced,and the applications of surface modified PLMs in biosensing and bioimaging as well as their challenges are summarized.

In vivo dissolution of poorly water-soluble drugs:Proof of concept based on fluorescence bioimaging

In vitro-in vivo correlation(IVIVC)of solid dosage forms should be established basically between in vitro and in vivo dissolution of active pharmaceutical ingredients.Nevertheless,in vivo dissolution profles have never been accurately portrayed.The current practice of IVIVC has to resort to in vivo absorption fractions(Fa).In this proof-of-concept study,in vivo dissolution of a model poorly watersoluble drug fenofbrate(FNB)was investigated by fuorescence bioimaging.FNB crystals were frst labeled by near-infrared fuorophores with aggregation-caused quenching properties.The dyes illuminated FNB crystals but quenched immediately and absolutely once been released into aqueous media,enabling accurate monitoring of residual drug crystals.The linearity established between fuorescence and crystal concentration justifed reliable quantifcation of FNB crystals.In vitro dissolution was frst measured following pharmacopoeia monograph protocols with well-documented IVIVC.The synchronicity between fuorescence and in vitro dissolution of FNB supported using fuorescence as a measure for determination of dissolution.In vitro dissolution correlated well with in vivo dissolution,acquired by either live or ex vivo imaging.The newly established IVIVC was further validated by correlating both in vitro and in vivo dissolution with Faobtained from pharmacokinetic data.

Design strategy and bioimaging of small organic molecule multicolor fluorescent probes

Multicolor fluorescent probes based on small organic molecules have the advantages of low cost, good biocompatibility, easily modifiable molecular structures and adjustable fluorescence performance. In addition, small molecule multicolor fluorescent probes generally undergo multi-site or multi-step reactions, which means that they can be used for the specific detection of structurally similar substances in complex bio-systems. In this review, we focus on the design and application of multicolor fluorescent probes based on small organic molecules: single fluorophores with multiple reaction sites, multiple fluorophores with single reaction sites, or multiple fluorophores with multiple reaction sites. Moreover, a design strategy for multicolor fluorescent probes and its application in biological imaging are also summarized, providing a systematic plan for future research on fluorescent probes functionalized by small organic molecules. It will also play an important role in the development of additional functions for small organic molecule fluorescent probes.

NIR-IIb excitable bright polymer dots with deep-red emission for in vivo through-skull three-photon fluorescence bioimaging

It is of great significance to study the brain structure and function in deep-tissue for neuroscience research and bio-medical applications because of the urgent demand for precise theranostics.Three-photon fluorescence microscopic(3PFM)bioimaging excited by the light in near-infrared IIb(NIR-IIb,1,500–1,700 nm)spectral region is one of the most promising imaging techniques with the advantages of high spatial resolution,large imaging depth,and reduced scattering.Herein,a type of NIR-IIb light excitable deep-red emissive semiconducting polymer dots(P-dots)with bright 3PF and large three-photon absorption cross-section(σ3)at 1,550 nm was prepared.Then the P-dots were functionalized with polystyrene polymer polystyrene graft ethylene oxide functionalized with carboxyl groups(PS-PEG-COOH)and modified with NH2-poly(ethylene glycol)(PEG)to synthesis photochemically stable and biocompatible P-dots nanoparticles(NPs).Further the P-dots NPs were utilized for in vivo 3PFM bioimaging of cerebral vasculature with and without the brain skull under 1,550 nm femtosecond(fs)laser excitation.In vivo 3PFM bioimaging of the mice cerebral vasculature at various vertical depths was obtained.Moreover,a vivid three-dimensional structure of the mice vascular architecture beneath the skull was reconstructed.At the depth of 350μm beneath the brain skull,3.8μm blood vessels could still be clearly recognized.NIR-IIb excitable P-dots assisted 3PFM bioimaging has great potential in accurate deep tissue bioimaging.

Fluorescence turn-on chemosensor for Hg^(2+) based on a rhodamine derivative and its application in bioimaging

A fluorescence turn-on chemosensor based on rhodamine B derivative (FD10) has been developed as a highly sensitive chemosensor for Hg2+. A prominent fluorescence enhancement was measured in the presence of Hg2+, which was in agreement with the changes in the absorption spectrum. Furthermore, by means of laser scanning fluorescence microscopy experiments, it was demonstrated that FD10 was cell-permeable and could be used as a fluorescent probe for monitoring Hg2+ in living cells.