Bio-assembled smart nanocapsules for targeted delivery of KRAS shRNA and cancer cell bioimage

The five-year survival rate for pancreatic cancer is less than 5%. However, the current clinical multimodal therapy combined with first-line chemotherapy drugs only increases the patient’s median survival from 5.0 months to 7.2 months. Consequently, a new strategy of cancer treatments is urgently needed to overcome this high-fatality disease. Through a series of biometric analyses, we found that KRAS is highly expressed in the tumor of pancreatic cancer patients, and this high expression is closely related to the poor prognosis of patients. It shows that inhibiting the expression of KRAS has great potential in gene therapy for pancreatic cancer. Given those above, we have exploited the possibility of targeted delivery of KRAS shRNA with the intelligent and bio-responsive nanomedicine to detect the special oxidative stress microenvironment of cancer cells and realize efficient cancer theranostics. Our observations demonstrate that by designing the smart self-assembled nanocapsules of melanin with fluorescent nanoclusters we can readily achieve the bio-recognition and bioimaging of cancer cells in biological solution or serum.The self-assembled nanocapsules can make a significant bio-response to the oxidative stress microenvironment of cancer cells and generate fluorescent zinc oxide Nanoclusters in situ for targeted cell bioimaging. Moreover, it can also readily facilitate cancer cell suppression through the targeted delivery of KRAS shRNA and low-temperature hyperthermia. This raises the possibility to provide a promising theranostics platform and self-assembled nanomedicine for targeted cancer diagnostics and treatments through special oxidative stress-responsive effects of cancer cells.

Bioimage-based protein subcellular location prediction： a comprehensive review

Subcellular localization of proteins can provide key hints to infer their functions and structures in cells. With the breakthrough of recent molecule imaging techniques, the usage of 2D bioimages has become increasingly popular in automatically analyzing the protein subcellular location pat- terns. Compared with the widely used protein 1D amino acid sequence data, the images of protein distribution are more intuitive and interpretable, making the images a better choice at many applications for revealing the dynamic char- acteristics of proteins, such as detecting protein translocation and quantification of proteins. In this paper, we systemati- cally reviewed the recent progresses in the field of automated image-based protein subcellular location prediction, and clas- sified them into four categories including growing of bioim- age databases, description of subcellular location distribution patterns, classification methods, and applications of the pre- diction systems. Besides, we also discussed some potential directions in this field.

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.

A novelα-ketoamide reactivity-based two-photon fluorogenic probe for visualizing peroxynitrite in Parkinson's disease models

Peroxynitrite(ONOO^(-))contributes to oxidative stress and neurodegeneration in Parkinson's disease(PD).Developing a peroxynitrite probe would enable in situ visualization of the overwhelming ONOO^(-)flux and understanding of the ONOO^(-)stress-induced neuropathology of PD.Herein,a novelα-ketoamide-based fluorogenic probe(DFlu)was designed for ONOO^(-)
monitoring in multiple PD models.The results demonstrated that DFlu exhibits a fluorescence turn-on response to ONOO^(-)with high specificity and sensitivity.The efficacy of DFlu for intracellular ONOO^(-)
imaging was demonstrated systematically.The results showed that DFlu can successfully visualize endogenous and exogenous ONOO^(-)in cells derived from chemical and biochemical routes.More importantly,the two-photon excitation ability of DFlu has been well demonstrated by monitoring exogenous/endogenous ONOO^(-)production and scavenging in live zebraflsh PD models.This work provides a reliable and promising
α-ketoamide-based optical tool for identifying variations of ONOO^(-)in PD models.

Recent Advances of Persistent Luminescence Nanoparticles in Bioapplications

Persistent luminescence phosphors are a novel group of promising luminescent materials with afterglow properties after the stoppage of excitation.In the past decade,persistent luminescence nanoparticles(PLNPs)with intriguing optical properties have attracted a wide range of attention in various areas.Especially in recent years,the development and applications in biomedical fields have been widely explored.Owing to the efficient elimination of the autofluorescence interferences from biotissues and the ultra-long near-infrared afterglow emission,many researches have focused on the manipulation of PLNPs in biosensing,cell tracking,bioimaging and cancer therapy.These achievements stimulated the growing interest in designing new types of PLNPs with desired superior characteristics and multiple functions.In this review,we summarize the works on synthesis methods,bioapplications,biomembrane modification and biosafety of PLNPs and highlight the recent advances in biosensing,imaging and imaging-guided therapy.We further discuss the new types of PLNPs as a newly emerged class of functional biomaterials for multiple applications.Finally,the remaining problems and challenges are discussed with suggestions and prospects for potential future directions in the biomedical applications.

A Review on Graphene-Based Nanomaterials in Biomedical Applications and Risks in Environment and Health

Graphene-based nanomaterials(GBNs) have attracted increasing interests of the scientific community due to their unique physicochemical properties and their applications in biotechnology, biomedicine, bioengineering, disease diagnosis and therapy. Although a large amount of researches have been conducted on these novel nanomaterials, limited comprehensive reviews are published on their biomedical applications and potential environmental and human health effects. The present research aimed at addressing this knowledge gap by examining and discussing:(1) the history, synthesis,structural properties and recent developments of GBNs for biomedical applications;(2) GBNs uses as therapeutics,drug/gene delivery and antibacterial materials;(3) GBNs applications in tissue engineering and in research as biosensors and bioimaging materials; and(4) GBNs potential environmental effects and human health risks. It also discussed the perspectives and challenges associated with the biomedical applications of GBNs.

Photostable and Biocompatible Fluorescent Silicon Nanoparticles for Imaging-Guided Co-Delivery of siRNA and Doxorubicin to Drug-Resistant Cancer Cells

The development of effective and safe vehicles to deliver small interfering RNA(siRNA) and chemotherapeutics remains a major challenge in RNA interference-based combination therapy with chemotherapeutics,which has emerged as a powerful platform to treat drug-resistant cancer cells.Herein,we describe the development of novel all-in-one fluorescent silicon nanoparticles(SiNPs)-based nanomedicine platform for imaging-guided co-delivery of siRNA and doxorubicin(DOX).This approach enhanced therapeutic efficacy in multidrug-resistant breast cancer cells(i.e.,MCF-7/ADR cells).Typically,the SiNP-based nanocarriers enhanced the stability of siRNA in a biological environment(i.e.,medium or RNase A) and imparted the responsive release behavior of siRNA,resulting in approximately 80% down-regulation of P-glycoprotein expression.Co-delivery of P-glycoprotein siRNA and DOX led to>35-fold decrease in the half maximal inhibitory concentration of DOX in comparison with free DOX,indicating the pronounced therapeutic efficiency of the resultant nanocomposites for drug-resistant breast cancer cells.The intracellular time-dependent release behaviors of siRNA and DOX were revealed through tracking the strong and stable fluorescence of SiNPs.These data provide valuable information for designing effective RNA interference-based co-delivery carriers.

Insights into Theranostic Properties of Titanium Dioxide for Nanomedicine

Titanium dioxide(TiO2)nanostructures exhibit a broad range of theranostic properties that make them attractive for biomedical applications.TiO2 nanostructures promise to improve current theranostic strategies by leveraging the enhanced quantum confinement,thermal conversion,specific surface area,and surface activity.This review highlights certain important aspects of fabrication strategies,which are employed to generate multifunctional TiO2 nanostructures,while outlining post-fabrication techniques with an emphasis on their suitability for nanomedicine.The biodistribution,toxicity,biocompatibility,cellular adhesion,and endocytosis of these nanostructures,when exposed to biological microenvironments,are examined in regard to their geometry,size,and surface chemistry.The final section focuses on recent biomedical applications of TiO2 nanostructures,specifically evaluating therapeutic delivery,photodynamic and sonodynamic therapy,bioimaging,biosensing,tissue regeneration,as well as chronic wound healing.

Ⅰ-Ⅲ-Ⅵ chalcogenide semiconductor nanocrystals:Synthesis,properties,and applications

Colloidal semiconductor nanocrystals have been proven to be promising candidates for applications in low‐cost and high‐performance photovoltaics,bioimaging,and photocatalysis due to their novel size‐and shape‐dependent properties.Among the colloidal systems,I‐III‐VI semiconductor nanocrystals(NCs)have drawn much attention in the past few decades.Compared to binary NCs,ternary I‐III‐VI NCs not only exhibit low toxicity,but also a high performance similar to that of binary NCs.In this review,we mainly focus on the synthesis,properties,and applications of I‐III‐VI NCs.We summarize the major synthesis methods,analyze their photophysical and electronic properties,and highlight some of the latest applications of I‐III‐VI NCs in solar cells,light‐emitting diodes,bioimaging,and photocatalysis.Finally,based on the information reviewed,we highlight the existing problems and challenges.

Fluorescence lifetime imaging of fluorescent proteins as an effective quantitative tool for noninvasive study of intracellular processes

Fluorescence litime imaging(FLIM)is an effective noninvasive bioanalytical tol based onmeasuring fuorescent lifetime of fuorophores.A growing number of FLIM studies utilizes ge-netically engineered fluorescent proteins targeted to specific subcellular structures to probe localmolecular environment,which opens new directions in cell science.This paper highlights theunconventional applications of FLIM for studies of molecular processes in diverse organelles oflive cultured cells.

Biomass-Derived Carbon Dots and Their Applications

Carbon dots(CDs) have received much attention due to their superior properties including water solubility, low toxicity, biocompatibility, small size,fluorescence, and ease of modification. The use of a more environmentally friendly method to prepare high-quality CDs is still an urgent question waiting for solve. The use of renewable, inexpensive, and green biomass resources not only meets the urgent need for large-scale synthesis biomass CDs(BCDs), but also promotes the development of sustainable applications.In this article, we summarize the representative methods for synthesizing BCDs in green and simple ways using biomass as a carbon source, including hydrothermal carbonization, and microwave, pyrolysis. The prepared BCDs have a uniform particle size distribution and a relatively high throughput,which provide a method to scale up industrial production. Moreover, the integration of specific optical properties, that is, tunable photoluminescence and up-photoluminescence, has led to remarkable use in bioimaging, sensing,and drug delivery. But the current review is not particularly comprehensive for BCDs. Therefore, we now provide a review focusing on the synthesis,properties, and recent advances in BCDs in biosensing, bioimaging,optoelectronics, and catalytic applications.

Labeling of influenza viruses with synthetic fluorescent and biotin-labeled lipids

Direct labeling of virus particles is a powerful tool for the visualization of virus–cell interaction events. However, this technique involves the chemical modification of viral proteins that affects viral biological properties. Here we describe an alternative approach of influenza virus labeling that utilizes Function-Spacer-Lipid(FSL) constructs that can be gently inserted into the virus membrane. We assessed whether labeling with fluorescent(fluo-Ad-DOPE) or biotin-labeled(biot-CMG2-DOPE) probes has any deleterious effect on influenza virus hemagglutinin(HA) receptor specificity, neuraminidase(NA) activity, or replicative ability in vitro. Our data clearly show that neither construct significantly affected influenza virus infectivity or viral affinity to sialyl receptors. Neither construct influenced the NA activities of the influenza viruses tested, except the A/Puerto Rico/8/34(H1N1) strain. Our data indicate that lipid labeling provides a powerful tool to analyze influenza virus infection in vitro.

Upconversion nanoparticle as a theranostic agent for tumor imaging and therapy

Upconversion nanoparticles(UCNPs)as a promising material are widely studied due to their unique optical properties.The material can be excited by long w avelength light and emit visible wavelength light through multiphoton absorption.This property makes the particles highly attractive candidates for bioimaging and therapy application.This review aims at summarizing the synthesis and modification of UCNPs,especially the applications of UCNPs as a theranostic agent for tumor imaging and therapy.The biocompatibility and toxicity of UCNPs are also further discussed.Finally,we discuss the challenges and opportunities in the development of UCNP-based nanoplatforms for tumor imaging and therapy.

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.

Review of Carbon Dots from Lignin: Preparing, Tuning, and Applying

Carbon dots(CDs),emerging carbon materials with unique physical and chemical properties,have drawn extensive attention from researchers.In recent years,many carbon sources have been used as precursors for preparing CDs.In contrast to other types of precursors,lignin,as a renewable and available source of natural aromatic biopolymers,is believed to be a low-cost precursor for the large-scale preparation of CDs.However,the preparation of CDs with excellent optical properties from lignin has some drawbacks because of the complex structure of lignin.Hence,the methods for preparing the CDs from lignin are summarized in this paper,and the mechanism and physical and chemical properties of lignin-based CDs are discussed.Moreover,some approaches to tuning the optical properties of lignin-based CDs have been proposed.Additionally,the use of lignin-based CDs in the fields of sensing,supercapacitor,bioimaging,anti-counterfeiting,and information encryption is reviewed.

Refocusing and locating effect of fluorescence scattering field

Optical imaging deep inside scattering medium has always been one of the challenges in the field of bioimaging,which significantly drawbacks the employment of con-focal microscopy system.Although a variety of feedback techniques,such as acoustic or nonlinear fluorescence-based schemes have realized the refocusing of the coherent light,the problems of non-invasively refocusing and locating of linearly-excited fluorescent beads inside the scattering medium have not been thoroughly explored.In this paper,we linearly excited the fluorescent beads inside a scattering medium by using our homemade optical con-focal system,collected the fluorescence scattering light as the optimized target,and established a theoretical model of target contrast enhancement,which is consistent with the experimental data.By improving both the cost function and variation rate within the genetic algorithm,we could refocus the fluorescence scattering field while improving the contrast enhancement factor to 12.8 dB.Then,the positions of the fluorescent beads are reconstructed by subpixel accuracy centroid localization algorithm,and the corresponding error is no more than 4.2μm with several fluorescent beads within the field of view.Finally,the main factors such as the number of fluorescent beads,the thickness of the scattering medium,the modulating parameter,the experimental noise and the system long-term stability are analyzed and discussed in detail.This study proves the feasibility of reconstructing fluorescent labeled cells inside biological tissues,which provides certain reference value for deep imaging of biological tissues.

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.

Fabrication of Excitation-Independent Green Emissive Graphene Quantum Dots for Selective Detection of Hg^(2+) and Fluorescence Imaging of Biothiols in Living Cells

Nitrogen-doped graphene quantum dots( N-GQDs)exhibiting excitation-independent green fluorescence emission( 536 nm) was facilely synthesized. The as-prepared N-GQDs showed a highly selective fluorescence quenching response toward Hg2 + with a linear range of 0. 1-30. 0 μmol/L and detection limit of50 nmol/L. Based on the high affinity of biothiols( such as cysteine)toward Hg2 +, the quenched fluorescence of N-GQDs could be recovered upon addition of biothiols,and thereby a new fluorescence turn-on probe for cysteine detection was further developed. The linear range and detection limit for cysteine were found to be 0. 1-12. 5 μmol/L and 46 nmol/L,respectively. The present fluorescent probe worked well in a physiological pure water medium,allowing a fluorescence imaging of cysteine in living cells.