Recent advances in near-infrared I/II persistent luminescent nanoparticles for biosensing and bioimaging in cancer analysis.

Photoluminescent materials (PLNs) are photoluminescent materials that can absorb external excitation light, store it, and slowly release it in the form of light in the dark to achieve long-term luminescence. Developing near-infrared (NIR) PLNs is critical to improving long-afterglow luminescent materials. Because they excite in vitro, NIR-PLNs have the potential to avoid interference from in vivo autofluorescence in biomedical applications. These materials are promising for biosensing and bioimaging applications by exploiting the near-infrared biological window. First, we discuss the biomedical applications of PLNs in the first near-infrared window (NIR-I, 700-900 nm), which have been widely developed and specifically introduce biosensors and imaging reagents. However, the light in this area still suffers from significant light scattering and tissue autofluorescence, which will affect the imaging quality. Over time, fluorescence imaging technology in the second near-infrared window (NIR-II, 1000-1700 nm) has also begun to develop rapidly. NIR-II fluorescence imaging has the advantages of low light scattering loss, high tissue penetration depth, high imaging resolution, and high signal-to-noise ratio, and it shows broad application prospects in biological analysis and medical diagnosis. This critical review collected and sorted articles from the past 5 years and introduced their respective fluorescence imaging technologies and backgrounds based on the definitions of NIR-I and NIR-II. We also analyzed the current advantages and dilemmas that remain to be solved. Herein, we also suggested specific approaches NIR-PLNs can use to improve the quality and be more applicable in cancer research.

Near-infrared-emitting persistent luminescent nanoparticles modified with gold nanorods as multifunctional probes for detection of arsenic(III).

Near infrared (NIR)-emitting persistent luminescent nanoparticles (PLNPs) have advantages such as long afterglow, high photostability and deep tissue spectral penetration. A NIR-emitting inner filter effect (IFE) probe for arsenic(III) is described here. It is composed of polyethyleneimine-coated PLNPs and gold nanorods (AuNPs) coated with dithiothreitol. The probe can detect arsenic(III) (= arsenite) selectively even in the presence of interfering substances. The PLNPs and AuNPs were prepared by a hydrothermal method combined with high-temperature calcination and seed-mediated growth mechanism, respectively. The PLNPs show excellent NIR luminescence (with excitation/emission peaks at 254/695 nm) and long afterglow (lifetime >1200 s). The use of polyethyleneimine improves water solubility and provides positive surface charges for the PLNPs. On exposure to arsenite ions, the luminescence of the probe at 695 nm is restored. Under the optimum conditions, the method can detect As(III) in the 0.067 to 13.4 µmol·L-1 concentration range with good linear relationship (R2 = 0.99734), and the detection limit (at S/N = 3) is 55 nmol·L-1. The precision of this method was demonstrated by 11 replicate detections of 2 µmol·L-1 As(III), and the relative standard deviations (RSD) is 2.1%. The practicality was evaluated by the analyses of real water samples and recoveries for the water samples spiked with 2, 5 and 10 µmol·L-1 of As(III) were 89.8%-100.1% with RSDs ranging from 3.0-5.7%. Graphical abstract A near infrared-emitting inner filter effect (IFE) inhibition probe is presented. It is based on the combination of polyethyleneimine (PEI)-coated NIR-emitting persistent luminescent nanoparticles (type Zn1.25Ga1.5Ge0.25O4: Cr3+, ZGGO) (PLNPs-PEI) with dithiothreitol (DTT)-coated gold nanorods (AuNPs) (DTT-AuNPs) to detect arsenite.

FRET-based Solid-state Luminescent Glyphosate Sensor Using Calixarene-grafted Ruthenium(II)bipyridine Doped Silica Nanoparticles.

Calixarene-functionalized luminescent nanoparticles were successfully fabricated for the FRET-based selective and sensitive detection of the organophosphorus pesticide glyphosate (GP). p-Tert-butylcalix[4]arene was grafted on the surface of [Ru(bpy)3 ]2+ incorporated SiNps to produce self-assembled nanosensors (RSC). FRET was switched on in the presence of GP by means of energy transfer due to binding with p-tert-butylcalix[4]arene grafted on the surface of the RSC. The FRET efficiency of the GP-RSC system was increased gradually with the addition of GP. The FRET efficiency was evaluated as 87.69 % and a high binding affinity was established by the binding constant value, 1.16×107  M-1 , using a Langmuir binding isotherm plot. The estimated limit of detection (LOD) was 7.91×10-7  M, which was lower than the Environmental Protection Agency (EPA) recommendation. The probe also effectively responds to real sample analysis. The sensitivity and selectivity was realized due to the efficient FRET towards the fluorescence properties of the [Ru(bpy)3 ]2+ complex.

Functionalized rare earth-doped nanoparticles for breast cancer nanodiagnostic using fluorescence and CT imaging.

BACKGROUND: Breast cancer is the second leading cause of cancer death among women and represents 14% of death in women around the world. The standard diagnosis method for breast tumor is mammography, which is often related with false-negative results leading to therapeutic delays and contributing indirectly to the development of metastasis. Therefore, the development of new tools that can detect breast cancer is an urgent need to reduce mortality in women. Here, we have developed Gd2O3:Eu3+ nanoparticles functionalized with folic acid (FA), for breast cancer detection. RESULTS: Gd2O3:Eu3+ nanoparticles were synthesized by sucrose assisted combustion synthesis and functionalized with FA using EDC-NHS coupling. The FA-conjugated Gd2O3:Eu3+ nanoparticles exhibit strong red emission at 613 nm with a quantum yield of ~ 35%. In vitro cytotoxicity studies demonstrated that the nanoparticles had a negligible cytotoxic effect on normal 293T and T-47D breast cancer cells. Cellular uptake analysis showed significantly higher internalization of FA-conjugated RE nanoparticles into T-47D cells (Folr hi ) compared to MDA-MB-231 breast cancer cells (Folr lo ). In vivo confocal and CT imaging studies indicated that FA-conjugated Gd2O3:Eu3+ nanoparticles accumulated more efficiently in T-47D tumor xenograft compared to the MDA-MB-231 tumor. Moreover, we found that FA-conjugated Gd2O3:Eu3+ nanoparticles were well tolerated at high doses (300 mg/kg) in CD1 mice after an intravenous injection. Thus, FA-conjugated Gd2O3:Eu3+ nanoparticles have great potential to detect breast cancer. CONCLUSIONS: Our findings provide significant evidence that could permit the future clinical application of FA-conjugated Gd2O3:Eu3+ nanoparticles alone or in combination with the current detection methods to increase its sensitivity and precision.

Construction of an autofluorescence interference-free phosphorescence biosensor for the specific detection of TK1 mRNA.

The anti-interference ability of biosensors is critical for detection in biological samples. Fluorescence-based sensors are subject to interference from self-luminescent substances in biological matrices. Therefore, phosphorescent sensors stand out among biosensors due to their lack of self-luminescence background. In this study, a phosphorescent sensor was constructed, which can accurately detect thymidine kinase 1 (TK1) mRNA in biological samples and avoid autofluorescence interference. When there is no target, polydopamine (PDA) is used as the phosphorescence resonance energy transfer (PRET) acceptor to quench the phosphorescence of the persistently luminescent (PL) nanomaterial. When there is a target, the DNA modified by the PL nanomaterial is replaced by the hairpin H and removed away from the PDA, resulting in a rebound in phosphorescence. The phosphorescent sensor exhibits a good linear relationship in the TK1 mRNA concentration range of 0-200 nM, and the detection limit was 1.74 nM. The sensor fabricated in this study can effectively avoid interference from spontaneous fluorescence in complex biological samples, and sensitively and precisely detect TK1 mRNA in serum samples, providing a powerful tool to more accurately detect biomarkers in biological samples.

Folic acid-mediated enhancement of the diagnostic potential of luminescent europium-doped hydroxyapatite nanocrystals for cancer biomaging.

Early and accurate cancer diagnosis is crucial for improving patient survival rates. Luminescent nanoparticles have emerged as a promising tool in fluorescence bioimaging for cancer diagnosis. To enhance diagnostic accuracy, ligands promoting endocytosis into cancer cells are commonly incorporated onto nanoparticle surfaces. Folic acid (FA) is one such ligand, known to specifically bind to folate receptors (FR) overexpressed in various cancer cells such as cervical and ovarian carcinoma. Therefore, surface modification of luminescent nanoparticles with FA can enhance both luminescence efficiency and diagnostic accuracy. In this study, luminescent europium-doped hydroxyapatite (EuHAp) nanocrystals were prepared via hydrothermal method and subsequently modified with (3-Aminopropyl)triethoxysilane (APTES) followed by FA to target FR-positive human cervical adenocarcinoma cell line (HeLa) cells. The sequential grafting of APTES and then FA formed a robust covalent linkage between the nanocrystals and FA. Rod-shaped FA-modified EuHAp nanocrystals, approximately 100 nm in size, exhibited emission peaks at 589, 615, and 650 nm upon excitation at 397 nm. Despite a reduction in photoluminescence intensity following FA modification, fluorescence microscopy revealed a remarkable 120-fold increase in intensity compared to unmodified EuHAp, attributed to the enhanced uptake of FA-modified EuHAp. Additionally, confocal microscope observations confirmed the specificity and the internalization of FA-modified EuHAp nanocrystals in HeLa cells. In conclusion, the modification of EuHAp nanocrystals with FA presents a promising strategy to enhance the diagnostic potential of cancer bioimaging probes.

Perspective and Prospects on persistent luminescent nanoparticles for biological imaging and tumor therapy.

Persistent luminescent nanoparticles (PLNPs) are photoluminescent materials that can still emit luminescence after the cessation of the excitation light source. In recent years, due to their unique optical properties, the PLNPs have attracted extensive attention in the biomedical field. Since the PLNPs effectively eliminate autofluorescence interference from biological tissues, many researchers have contributed a lot of work in the fields of biological imaging and tumor therapy. This article mainly introduces the synthesis methods of the PLNPs and their progress in the application of biological imaging and tumor therapy, as well as the challenges and development prospects.

pH-Responsive Plasmon-Enhanced Persistent Luminescent ZnGa2O4:Cr3+ Nanopomegranate for Tumor Imaging.

Noble metal compositing is a promising method to enhance radiance intensity of persistent luminescent (PersL) nanoparticles (NPs) via surface plasmon resonance (SPR) for better tumor imaging, but it rarely unites with the pH-response strategy due to the challenge of realizing rigorous pH-responsive spatial distance control as a "button switch" of SPR. Here, ZnGa2O4:Cr3+ (ZGC) NPs as "pomegranate seeds" are cladded with sodium alginate to form nanoclusters (ZGC-SA), subsequently coated with carboxyl-rich polymers to acquire "pomegranate rind" (ZSPB) and finally decorated with 10 nm gold NPs (AuNPs) on the surface to obtain nanopomegranate structure (ZSPB@AuNPs). Though without deliberate distance control, there are plenty of "seeds" inside ZSPB@AuNPs fortunately at appropriate positions, which could be plasmon-enhanced by AuNPs. Furthermore, triggered by carboxyl protonation in subacid tumor, ZSPB@AuNPs aggregate and subsequently facilitate such plasmon enhancement effect, resulting in 4.4-fold PersL promotion at pH 5.5 (tumor microenvironment, TME) over pH 7.4 and in a maximum "tumor to normal tissue ratio" of PersL imaging signals of 125.9. Under surgical navigation of ZSPB@AuNPs, intramuscular tumors of mice could be resected without residue signals left. This nanopomegranate achieves TME pH-responsive plasmon-enhanced PersL for the first time and broadens the way for designing plasmon-enhanced PersL nanosystems.

Exogenous interference and autofluorescence-free ratiometric aptasensor for detection of OTA based on dual-colored persistent luminescence nanoparticles.

Accurate and sensitive detection of ochratoxin A (OTA) is highly necessary due to its high carcinogenicity, teratogenicity and mutagenicity. Herein, we reported an exogenous interference and autofluorescence-free ratiometric aptasensor based on dual-colored persistent luminescent nanoparticles for precise detection of OTA. Green-emitting ZnGeO:Mn bonded with OTA aptamer and BHQ1-modified complementary base was acted as detection and specific recognition probe (ZGM@BHQ1). Quaternary ammonium modified ZnGaGeO:Cr with red emission was employed as reference probe and further bonded to ZGM@BHQ1 through electrostatic interaction to construct the ratiometric aptasensor. The developed ratiometric aptasensor was free from real-time excitation, external interference and autofluorescence and gave low detection limit of 3.4 pg mL-1, wide linearity in the range of 0.01-50 ng mL-1 and high precision of 3.1 % (11 replicate determinations, at 1 ng mL-1 level). The applicability of the aptasensor was successfully demonstrated by analyzing OTA in in grain samples with recoveries of 97.6 %-105.2 %.

Time-Gated Imaging of Latent Fingerprints with Level 3 Details Achieved by Persistent Luminescent Fluoride Nanoparticles.

The discovery of X-ray-charged persistent luminescence (PersL) in fluoride nanoparticles enables these materials to emit photons without real-time excitation, which provides a great possibility for the development of new luminescent nanotechnologies. In this work, we developed NaLuF4:Mn nanoparticles with intense green PersL and functionalized surfaces and accordingly achieved time-gated imaging of latent fingerprints (LFPs) with Level 3 details. These surface-modified NaLuF4:Mn nanoparticles exhibited near-spherical morphology, long-lasting emission for several hours, appropriate trap depth distribution, and tight chemical bonding with amino acids from fingerprints, thus greatly improving the accuracy of LFP imaging in a variety of environments. The developed NaLuF4:Mn PersL nanoparticles are expected to find broad applications in the fields of LFP imaging and in vivo biological imaging.

Quantitative considerations about the size dependence of cellular entry and excretion of colloidal nanoparticles for different cell types.

Most studies about the interaction of nanoparticles (NPs) with cells have focused on how the physicochemical properties of NPs will influence their uptake by cells. However, much less is known about their potential excretion from cells. However, to control and manipulate the number of NPs in a cell, both cellular uptake and excretion must be studied quantitatively. Monitoring the intracellular and extracellular amount of NPs over time (after residual noninternalized NPs have been removed) enables one to disentangle the influences of cell proliferation and exocytosis, the major pathways for the reduction of NPs per cell. Proliferation depends on the type of cells, while exocytosis depends in addition on properties of the NPs, such as their size. Examples are given herein on the role of these two different processes for different cells and NPs.

Influence of NaYF4 Inert and Active Layer on Upconversion Luminescence.

NaYF4:Yb,Er@NaYF4 core-shell nanostructures were prepared to investigate their influence on upconversion (UC) luminescence. Tests revealed green radiation (4S3/2→4I15/2) and red radiation (4F9/2→4I15/2) first increased and then gradually decreased as Yb concentration increased in the NaYF4 shell. The strongest fluorescent radiation occurred at an Yb concentration of 5%. To investigate the complicated variation of luminescence, we designed a set of experiments to study the impact of Yb ion concentration on luminescence intensity, and we analyzed the corresponding enhancement mechanism. It is probable that the energy transfers between both Yb and Er ions and Yb and Yb ions are involved in the UC processes. The enhancement of hybrid nanostructures has huge potential in biological detection and solar cells.

Facile and Controllable Synthesis of the Renal-Clearable "Luminous Pearls" for in Vivo Afterglow/Magnetic Resonance Imaging.

To date, the strategic exploration of a synthetic approach to afford persistent luminescent nanoparticles (PLNPs) integrated with precisely controlled size/monodispersity and renal-clearable capability remains extremely challenging. Herein, we report a facile synthetic process with an elucidated mechanism to fine-tune the size for acquiring renal-clearable PLNPs, using mesoporous silica nanoparticles (MSNs) as a template. This strategy relies on the controlled crystallization of the precursor ions in the pore channels of MSNs at a high temperature, leading to the formation of monodispersed PLNPs with an average diameter as small as 2.5 nm after complete removal of MSN templates. The as-prepared ultrasmall PLNPs coated with polyethylene glycol exhibit uniform size, excellent water-dispersibility, good persistent luminescence, and high T1 relaxivity (17.6 mM-1·S-1), ensuring their suitability for afterglow/magnetic resonance dual-modality imaging and subsequent in vivo renal clearance. Thus, our study provides a strategy to inspire the controlled synthesis of diverse PLNPs by using MSN templates, simultaneously addressing the critical issues of precise adjustment of size and body clearance for versatile biomedical applications.

Non-autofluorescence Detection of H5N1 Virus Using Photochemical Aptamer Sensors Based on Persistent Luminescent Nanoparticles.

Fluorescence sensing is limited in practical applications owing to multiple autofluorescent substances in complex biological samples such as serum. In this paper, the luminescence decay effect of persistent luminescent nanoparticles (PLNPs) was used to avoid the interference of autofluorescence in complex biological samples, and a non-autofluorescence molecularly imprinted polymer aptamer sensor (MIP-aptasensor) was designed to detect H5N1 virus. The proposed MIP-aptasensor consists of a magnetic MIP and aptamer-functionalized persistent luminescent nanoparticle Zn2GeO4:Mn2+-H5N1 aptamer (ZGO-H5N1 Apt). Upon simultaneous recognition of H5N1 virus, strong persistent luminescent signal changes were produced. Using the unique luminescent characteristics of PLNPs and the high selectivity of imprinted polymers and aptamers, the designed MIP-aptasensor effectively eliminates the autofluorescence background interference of serum samples and realizes the non-autofluorescence detection of H5N1 virus with high sensitivity (a limit of detection of 0.0128 HAU mL-1, 1.16 fM) and selectivity (the imprinting factor for the target H5N1 virus was 6.72). This tool provides a strategy for the design of sensors and their application in complex biological samples.

Ligand-Sensitised LaF3 :Eu3+ and SrF2 :Eu3+ Nanoparticles and in Vitro Haemocompatiblity Studies.

Luminescent Ln3+ -doped nanoparticles (NPs) functionalised with the desired organic ligand molecules for haemocompatibility studies were obtained in a one-pot synthesis. Chelated aromatic organic ligands such as isophthalic acid, terephthalic acid, ibuprofen, aspirin, 1,2,4,5-benzenetetracarboxylic acid, 2,6-pyridine dicarboxylic acid and adenosine were applied for surface functionalisation. The modification of the nanoparticles is based on the donor-acceptor character of the ligand-nanoparticle system, which is an alternative to covalent functionalisation by peptide bonding as presented in our recent report. The aromatic groups of selected ligands absorb UV light and transfer their excited-state energy to the dopant Eu3+ ions in LaF3 and SrF2 NPs. Herein, we discuss the structural and spectroscopic characterisation of the NPs and the results of haemocompatibility studies. Flow cytometry analysis of the nanoparticles' membrane-binding is also presented.

Targeted delivery of paclitaxel by NL2 peptide-functionalized on core-shell LaVO4: Eu3@ poly (levodopa) luminescent nanoparticles.

Targeted drug delivery enhances drug efficiency and selectivity without affecting normal cells. Luminescent nanoparticles can be used for tumor imaging as well as selective tumor targeting for drug delivery. In this research, LaVO4 :Eu3+ was synthesized, the luminescent nanocrystal was coated by surface polymerization of levodopa in the presence of Paclitaxel (PTX), and then NL2 peptide was coupled on the surface of polymer-coated luminescent nanoparticles. Next, the capability of the modified drug was examined by in vitro and in vivo experiments. MTT assay on SK-BR-3 cell line (as breast cancer cells) and fluorescent microscopy results indicate that this modification decreases significantly drug toxicity and increases its selectivity. In addition, in vivo experiments confirm more capability of the NL2-functionalized nanocomposite for reducing tumor size, drug distribution in the body, and more aggregation of PTX in tumor tissue. Overall, it is concluded that tumor imaging is possible using luminescent LaVO4 :Eu3+ core and NL2 peptide increases significantly the specificity of PTX in combination with a functionalized luminescent polymeric carrier.

Synthesis and Characterization of Green Carbon Dots for Scavenging Radical Oxygen Species in Aqueous and Oil Samples.

Carbon dots (CDs) due to their unique optical features, chemical stability and low environmental hazard are applied in different fields such as metal ion sensing, photo-catalysis, bio-imaging and tribology, among others. The aims of the present research were to obtain CDs from vegetable wastes (tea and grapes) as carbon sources and to explore their potential properties as radical scavengers. CDs from glutathione/citric acid (GCDs) were synthetized for comparison purposes. The CDs were investigated for their chemical structure, morphology, optical and electronical properties. The antioxidant activity has been explored by DPPH and Folin-Ciocelteau assays in aqueous media. Due to their solubility in oil, the CDs prepared from tea wastes and GCDs were assayed as antioxidants in a mineral oil lubricant by potentiometric determination of the peroxide value. CDs from tea wastes and GCDs exhibited good antioxidant properties both in aqueous and oil media. Possible mechanisms, such as C-addition to double bonds, H-abstraction and SOMO-CDs conduction band interaction, were proposed for the CDs radical scavenging activity. CDs from natural sources open new application pathways as antioxidant green additives.

Surface Modification of Luminescent LnIII Fluoride Core-Shell Nanoparticles with Acetylsalicylic acid (Aspirin): Synthesis, Spectroscopic and in Vitro Hemocompatibility Studies.

Luminescent lanthanide fluoride core-shell (LaF3 :Tb3+ ,Ce3+ @SiO2 -NH2 ) nanoparticles, with acetylsalicylic acid (aspirin) coated on the surface have been obtained. The synthesized products, which combine the potential located in the silica shell with the luminescent activity of the core, were characterized in detail with the use of luminescence spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and transmission electron microscopy (TEM) methods. The in vitro effects of the modified luminescent nanoparticles on human red blood cell (RBC) membrane permeability, RBC shape, and sedimentation rate were investigated to assess the hemocompatibility of the obtained compounds. This study demonstrates that LaF3 : Tb3+ 5 %, Ce3+ 10 %@SiO2 -NH2 nanoparticles with acetylsalicylic acid (aspirin) coated on the surface are very good precursors for multifunctional drug-delivery systems or bio-imaging probes that can be used safely in potential biomedical applications.

Protein-stabilized gold nanoclusters for PDT: ROS and singlet oxygen generation.

Suitable properties as well as eco-friendly synthesis of photoluminescent Au nanoclusters (NCs) make them promising compounds for biomedical diagnostics and visualization applications. However, the potential photochemical activity of such agents on cancerous cells is largely unknown. The nanoclusters (BSA-Au NCs) were synthetized in the presence of BSA (an average hydrodynamic diameter was about 9.4 nm, while the size of the metal cluster was <1.3 nm according to atomic force microscopy measurements) and possessed a broad photoluminescence band at 680 nm in buffered (pH 7.2) aqueous medium. The photochemical activity was studied by adding two fluorescent probes (dihydrorhodamine or Singlet Oxygen Sensor Green) for detection of reactive oxygen species in samples irradiated at 405 nm to minimize direct excitation of the probes. The photoluminescence measurements evidenced the capability of BSA-Au NCs to generate reactive oxygen species upon light exposure, while the observed sensitivity of the photoluminescence properties might be used to indicate photooxidative processes in the medium. The viability test performed on breast cancer cells after incubation with BSA-Au NCs and subsequent irradiation revealed notable difference in induced phototoxicity between two cell lines, which was not the case after the corresponding treatment using the photosensitizer chlorin e6.

Near infrared-emitting persistent luminescent nanoparticles for Hepatocellular Carcinoma imaging and luminescence-guided surgery.

Hepatocellular carcinoma (HCC), the fifth most common cancer worldwide, is increasing nowadays and poses a serious threat to human health. However, if treated effectively and timely, it is clinically manageable or curable. Therefore, accurate detection and complete surgical resection remain priorities for HCC with a high potential of improving both survival and quality of life. Lacking of real-time guide technology, traditional surgery are usually relied on the subjective experience of surgeon, which have the limitation of high sensitivity detection tumor. Here, we developed a contrast agent, ZnGa2O4Cr0.004 (ZGC), used for guided surgery during operation to accurate delineation of HCC. ZGC showed excellent long-lasting afterglow properties that lasted for hours, which can aid in real-time guided surgery. Meanwhile, ZGC display high spatial resolution and deep penetration during pre-operation for diagnostic computed tomography (CT). Interestingly, we observed reverse imaging in the tumor region, known as a "dark hole", which further improves the contrast for surgery. This new multi-modality nanoparticle has great potential for accurate liver cancer imaging and resection guidance.