Down-conversion Nanoparticles Research Articles

A Room-Temperature Strategy to Synthesize Ce/Tb-Codoped NaYF4 Nanoparticles with a Photoluminescence Quantum Yield Exceeding 50.

NaYF4:Ce3+,Tb3+ down-conversion nanoparticles with a photoluminescence quantum yield (PLQY) of 54.8% are synthesized by using a ligand-assisted coprecipitation method in this study. The reaction is completed within 1 min at room temperature, and short-chain hexanoic acid and hexylamine serve as the binary ligands, which enable us to synthesize highly luminescent NaYF4:Ce3+,Tb3+ nanoparticles at room temperature. X-ray diffraction (XRD) and transmission electron microscopy (TEM) are used to characterize the as-prepared nanocrystals. The results reveal that the NaYF4:Ce3+,Tb3+ nanocrystals exhibit excellent dispersion and have a particle size of 2.7 nm. Our NaYF4:Ce3+,Tb3+ nanocrystals possess the advantages of room-temperature preparation, high PLQY, and ultrasmall particle size. These results reveal that the NaYF4:Ce3+,Tb3+ nanocrystals might have a high potential in the applications of lighting, display devices, and bioimaging.

Activatable Nanoprobes for Dual‐Modal NIR‐II Photoacoustic and Fluorescence Imaging of Hydrogen Sulfide in Colon Cancer

AbstractHigh hydrogen sulfide (H2S) expression has been shown to play a crucial role in tumor growth and proliferation in colon cancer. So far, most probes used for monitoring H2S offer single‐modal imaging, which makes the collection of accurate information for tumor diagnosis difficult. In the present study, a novel dual‐modal imaging probe in the second near‐infrared (NIR‐II, 950‐1700) window is proposed and constructed by coating a uniform shell of polydopamine (PDA) on the surface of cuprous oxide (Cu2O)‐conjugated downconversion nanoparticles (DCNPs). Of note, DCNP‐Cu2O@PDA is in the “on” state, with emission centered at 1550 nm (irradiation using a 980nm laser) in non‐neoplastic tissues. Colon tumors with endogenous H2S overexpression can induce the in situ transformation of Cu2O to copper sulfide (Cu2‐XS）. Owing to the competitive absorption between Cu2‐XS and DCNPs at a wavelength of 980 nm, the generated DCNP‐Cu2‐XS@PDA exhibits a quenched NIR‐II fluorescence (FL) signal. Meanwhile, Cu2‐XS exhibits a strong absorbance at 1250 nm, enhancing the NIR‐II photoacoustic (PA) signal accompanied by NIR‐II FL attenuation. The switching in PA and FL signals at the tumor site offered “double assurances” for the accurate monitoring of H2S.

Shortwave-infrared-light-emitting probes for the in vivo tracking of cancer vaccines and the elicited immune responses.

Tracking and imaging immune cells in vivo non-invasively would offer insights into the immune responses induced by vaccination. Here we report a cancer vaccine consisting of polymer-coated NaErF4/NaYF4 core-shell down-conversion nanoparticles emitting luminescence in the near-infrared spectral window IIb (1,500-1,700 nm in wavelength) and with surface-conjugated antigen (ovalbumin) and electrostatically complexed adjuvant (class-B cytosine-phosphate-guanine). Whole-body wide-field imaging of the subcutaneously injected vaccine in tumour-bearing mice revealed rapid migration of the nanoparticles to lymph nodes through lymphatic vessels, with two doses of the vaccine leading to the complete eradication of pre-existing tumours and to the prophylactic inhibition of tumour growth. The abundance of antigen-specific CD8+ T lymphocytes in the tumour microenvironment correlated with vaccine efficacy, as we show via continuous-wave imaging and lifetime imaging of two intravenously injected near-infrared-emitting probes (CD8+-T-cell-targeted NaYbF4/NaYF4 nanoparticles and H-2Kb/ovalbumin257-264 tetramer/PbS/CdS quantum dots) excited at different wavelengths, and by volumetrically visualizing the three nanoparticles via light-sheet microscopy with structured illumination. Nanoparticle-based vaccines and imaging probes emitting infrared light may facilitate the design and optimization of immunotherapies.

Plasmonic‐Enhanced NIR‐II Downconversion Fluorescence beyond 1500 nm from Core–Shell–Shell Lanthanide Nanoparticles

AbstractThis paper reports on the light amplification of NaGdF4:Yb,Er,Ce@NaGdF4:Yb,Nd@NaGdF4 core–shell–shell downconversion nanoparticles (CSS‐DCNPs) in the near‐infrared second biological window (NIR‐II: 1000–1700 nm) by plasmonic nanostructures. Through a precisely controlled plasmonic metallic nanostructure, fluorescence from Yb3+ induced 1000 nm emission, Nd3+ induced 1060 nm emission, and Er3+ induced 1527 nm emission are enhanced 1.6‐fold, 1.7‐fold, and 2.2‐fold, respectively, under an 808 nm laser excitation for the CSS‐DCNPs coupled with a gold hole‐cap nanoarray (Au‐HCNA), while the Er3+ induced 1527 nm emission under a 980 nm laser excitation is enhanced up to 6‐fold. To gain insight into the enhancement mechanism, the plasmonic modulation of Er3+ induced NIR‐II emission at 1550 nm under 980 nm excitation is studied by FDTD simulation and lifetime measurements, showing the observed fluorescence enhancement can be attributed to a combination of enhanced excitation and an increased radiative decay rate.

Handheld NIR-to-NIR Platform for on-site evaluating protective neutralizing antibody against SARS-CoV-2 ancestral strain and Omicron variant after vaccination or infection

Lateral flow assays (LFAs) are promising points-of-care tests, playing a vital role in diseases screening, diagnosis and surveillance. However, development of portable, cheap, and smart LFAs platform for sensitive and accurate quantification of disease biomarkers in complex media is challenging. Here, a cheap handheld device was developed to realize on-site detection of disease biomarkers by Nd3+/Yb3+ co-doped near-infrared (NIR)-to-NIR downconversion nanoparticles (DCNPs) based LFA. Its sensitivity is at least 8-fold higher for detecting NIR light signal from Nd3+/Yb3+ co-doped nanoparticles than conventional expensive InGaAs camera based detection platform. Additionally, we enhance NIR quantum yield of Nd3+/Yb3+ co-doped nanoparticles up to 35.5% via simultaneous high dopant of sensitizer ions Nd3+ and emitter ions Yb3+. Combination of NIR-to-NIR handheld detection device and ultra-bright NIR emitting NaNbF4:Yb60%@NaLuF4 nanoparticle probe allows the detection sensitivity of SARS-CoV-2 ancestral strain and Omicron variants specific neutralizing antibodies LFA up to the level of commercial enzyme linked immunosorbent assay kit. Furthermore, by this robust method, enhanced neutralizing antibodies against SARS-CoV-2 ancestral strain and Omicron variants are observed in healthy participants with Ad5-nCoV booster on top of two doses of inactivated vaccine. This NIR-to-NIR handheld platform provides a promising strategy for on-site evaluating protective humoral immunity after SARS-CoV-2 vaccination or infection.

Near-Infrared Persistent Luminescence Nanoprobe for Ultrasensitive Image-Guided Tumor Resection.

Near-infrared (NIR) fluorescence imaging poses significant superiority over traditional medical imaging for tumor resection, thus having attracted widely attention. However, for tiny tumor residues, it requires relative high sensitivity to determine. Here, based on persistent luminescence nanoparticles (PLNPs), an ultrasensitive nanoprobe with extraordinary tumor imaging result is developed to guide surgical removal. Persistent luminescence (PersL) is quenched in normal tissue by the outer layer of MnO2 , and is recovered due to the degradation of MnO2 in tumor microenvironment, significantly improving the sensitivity of tumor imaging. Combined with the absence of background fluorescence in imaging of PLNPs, ultrahigh sensitivity is achieved. In orthotopic breast cancer model, the intraoperative tumor-to-normal tissue (T/NT) signal ratio of the nanoprobe is 58.8, about 9 times that of downconversion nanoparticles. The T/NT ratio of residual tumor (<2mm) remains 12.4, considerably high to distinguish tumor tissue from normal tissue. Besides, multiple-microtumor, 4T1 liver-implanted tumor and lung metastasis models are built to prove that this ultrasensitive nanoprobe is feasible to recognize tumor residues. Notably, PersL imaging takes only 1.5min, appropriate to be applied for intraoperative imaging. Overall, an ultrasensitive and convenient imaging for recognizing residual tumor tissue is introduced, holding promise for complete surgical removal.

NIR-IIb fluorescence-image guided synergistic surgery/starvation/chemodynamic therapy: an innovative treatment paradigm for malignant non-small cell lung cancers.

Background: Currently, the prognosis and survival rate for patients bearing non-small cell lung cancer (NSCLC) is still quite poor, mainly due to lack of efficient theranostic paradigms to exert in time diagnostics and therapeutics. Methods: Herein, for NSCLC treatment, we offer a customized theranostic paradigm, termed NIR-IIb fluorescence diagnosis and synergistic surgery/starvation/chemodynamic therapeutics, with a newly designed theranostic nanoplatform PEG/MnCuDCNPs@GOx. The nanoplatform is composed of brightly NIR-II emissive downconversion nanoparticles (DCNPs)-core and Mn/Cu-silica shell loaded with glucose oxidase (GOx) to achieve synergistic starvation and chemodynamic therapy (CDT). Results: It is found that 10% Ce3+ doped in the core and 100% Yb3+ doped in the middle shell greatly improves the NIR-IIb emission up to even 20.3 times as compared to the core-shell DCNPs without Ce3+ doping and middle shell. The bright NIR-IIb emission of the nanoplatform contributes to sensitive margin delineation of early-stage NSCLC (diameter < 1 mm) with a signal-to-background ratio (SBR) of 2.18, and further assists in visualizing drug distribution and guiding surgery/starvation/chemodynamic therapy. Notably, the starvation therapy mediated by GOx-driven oxidation reaction efficiently depletes intratumoral glucose, and supplies H2O2 to boost the CDT mediated by the Mn2+ and Cu2+, which consequently realized a highly effective synergistic treatment for NSCLC. Conclusion: This research demonstrates an efficient treatment paradigm for NSCLC with NIR-IIb fluorescence diganosis and image-guided synergistic surgery/starvation/chemodynamic therapeutics.

Microenvironment‐Tailored Catalytic Nanoprobe for Ratiometric NIR‐II Fluorescence/Photoacoustic Imaging of H2O2 in Tumor and Lymphatic Metastasis

AbstractIn vivo H2O2 visualization is crucial for disease diagnosis. Catalytic reaction‐based probes show potential in H2O2 detection, yet their in vivo application remains challenging because catalysts always require a specific pH to function and cellular glutathione (GSH) may suppress signaling by depletion of hydroxyl radicals and oxidized substrates. Here, a microenvironment‐tailored catalytic nanoprobe (MTCN) comprising Fe2+, citric acid (CA), 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) diammonium salt (ABTS), and downconversion nanoparticles in the liposomal cavity as well as a reference dye in the lipid membrane is reported, which utilizes the selective permeability of the liposomal membrane to offer a favorable pH for Fe2+ catalyst with the aid of CA and to avoid GSH‐triggered signal loss by preventing entry of GSH into the cavity. The MTCN displays a large NIR‐II fluorescence (FL) ratio between 1550 and 1080 nm (FL1550Em,808Ex/FL1080Em,980Ex), but a small photoacoustic (PA) ratio between 808 and 1048 nm (PA808/PA1048). Upon exposure of MTCN to H2O2, catalytic conversion of ABTS into its oxidized form ABTS·+ with 808 nm absorption causes a noticeable increment in PA808/PA1048 accompanied by an apparent decrement in FL1550Em,808Ex/FL1080Em,980Ex, enabling bimodal ratiometric imaging of H2O2 in the tumor and lymphatic metastasis.

Lanthanide/Cu2-xSe Nanoparticles for Bacteria-Activated NIR-II Fluorescence Imaging of Infection.

A material system enabling specific NIR-II fluorescence imaging of Gram-positive bacteria is described. The material system is based on the electrostatic binding of Cu2-xSe and vancomycin-modified NaGdF4:Nd,Yb@NaGdF4 downconversion nanoparticles (DCNPs), the fluorescence of which is weak owing to the spectral overlap of Cu2-xSe absorption with the DCNP NIR emission. The presence of Gram-positive bacteria precisely disconnects the bond between vancomycin-modified DCNPs and Cu2-xSe, thus enabling a strong fluorescent signal. In vivo studies show that the material system can be specifically activated at the site of Gram-positive bacterial infection but is essentially nonfluorescent in the area of Gram-negative bacterial infection.

Tracking Cell Viability for Adipose-Derived Mesenchymal Stem Cell-Based Therapy by Quantitative Fluorescence Imaging in the Second Near-Infrared Window.

Cell survival rate determines engraftment efficiency in adipose-derived mesenchymal stem cell (ADSC)-based regenerative medicine. In vivo monitoring of ADSC viability to achieve effective tissue regeneration is a major challenge for ADSC therapy. Here, we developed an activated near-infrared II (NIR-II) fluorescent nanoparticle consisting of lanthanide-based down-conversion nanoparticles (DCNPs) and IR786s (DCNP@IR786s) for cell labeling and real-time tracking of ADSC viability in vivo. In dying ADSCs due to excessive ROS generation, absorption competition-induced emission of IR786s was destroyed, which could turn on the NIR-II fluorescent intensity of DCNPs at 1550 nm by 808 nm laser excitation. In contrast, the NIR-II fluorescent intensity of DCNPs was stable at 1550 nm by 980 nm laser excitation. This ratiometric fluorescent signal was precise and sensitive for tracking ADSC viability in vivo. Significantly, the nanoparticle could be applied to quantitively evaluate stem cell viability in real-time in vivo. Using this method, we successfully sought two small molecules including glutathione and dexamethasone that could improve stem cell engraftment efficiency and enhance ADSC therapy in a liver fibrotic mouse model. Therefore, we provide a potential strategy for real-time in vivo quantitative tracking of stem cell viability in ADSC therapy.

Noninvasive and early diagnosis of acquired brain injury using fluorescence imaging in the NIR-II window.

Acquired brain injury (ABI), which is the umbrella term for all brain injuries, is one of the most dangerous diseases resulting in high morbidity and mortality, making it extremely significant to early diagnosis of ABI. Current methods, which are mainly composed of X-ray computed tomography and magnetic resonance angiography, remain limited in diagnosis of ABI with respect to limited spatial resolution and long scanning times. Here, we reported through-skull fluorescence imaging of mouse cerebral vasculature without craniotomy, utilizing the fluorescence of down-conversion nanoparticles (DCNPs) in the 1.3 - 1.7 μm near-infrared window (NIR-II window). Due to its high spatial resolution of 22.79 μm, the NIR-II fluorescence imaging method could quickly distinguish the brain injury region of mice after performing the stab wound injury (traumatic brain injury) and ischemic stroke (non-traumatic brain injury), enabling it a powerful tool in the noninvasive and early diagnosis of ABI.

NaGdF4:Nd@NaGdF4 Core-Shell Down-Conversion Nanoparticles as NIR-II Fluorescent Probes for Targeted Imaging of Bacteria

Bacterial infections are a serious ongoing threat to human health. As such, within the context of modern technology, there is an urgent need to develop fluorescent probes suitable for diagnosing bacterial infections in vivo. Herein, we synthesize NaGdF4:Nd@NaGdF4 core-shell down-conversion nanoparticles (DCNPs) demonstrating excellent emission intensity in the second near-infrared (NIR-II) window for use as fluorescent probes to enable high-quality imaging of pathogenic infections. The fluorescent probe is covalently linked with vancomycin (Van), which specifically binds to Gram-positive bacteria such as S. aureus. Both in vitro detection and in vivo imaging results show that the Van-modified NIR-II fluorescent probe can distinguish Gram-positive from Gram-negative bacteria with a high degree of selectivity. Biocompatibility is verified by MTT assay and histological analyses.

A Feasible and Facile Method for the Anticounterfeiting of Down Fiber

In order to prevent counterfeiting of down fiber from consumers, rare earth fluorescent materials are developed in the field of material identification and anticounterfeiting. Herein, the development of verifiable down fiber based on infrared excitation-infrared emission was described. A novel method was approached to prepare security down fiber, which involved modification of down-conversion nanoparticles (DCNPs) by sulfonic groups and self-assembly onto down fiber through electrostatic force. DCNPs were successfully prepared from ytterbium-deposited NaYF4 nanoparticles using a complexation precipitation approach, in which the trivalent ytterbium ions served as the luminescent center. Sulfonic down-conversion nanoparticles (SO3-SiO2@DCNPs) were fabricated by the hydrolysis of 3-mercaptopropyl triethoxysilane (MPTES) and next oxidation to enhance the combination of the DCNPs with down fiber. The synthesis of DCNPs and SO3-SiO2@DCNPs and its pendant to down were confirmed by XRD, SEM, XPS, FT-IR, Zeta potential meter, and PL, which revealed the presence of DCNPs in the size average 86 nm. The obtained DCNPs and security down fiber were launching an invisible red-shifted emission of 930∼1080 nm (corresponding to the 2F5/2 ⟶ 2F7/2 transitions in Yb3+). After washing, the infrared emission of security down fiber was evaluated and proved to be effective with fine results, which showed its potential application in the field of security.

In Vivo Tracking of Cell Viability for Adoptive Natural Killer Cell‐Based Immunotherapy by Ratiometric NIR‐II Fluorescence Imaging

AbstractThe therapeutic efficacy of natural killer (NK) cells‐based immunotherapy is greatly related with the survival of transplanted NK cells. However, no effective strategy was reported to monitor NK cell viability in adoptive immunotherapy in vivo. Herein, we develop a ratiometric NIR‐II fluorescence imaging strategy to quantitively track and visualize the adoptive NK cell viability in vivo in real‐time. The nanoprobe consists of lanthanide‐based down‐conversion nanoparticles (DCNP) coated with IR786s, a reactive oxygen species (ROS) sensitive to NIR dye, which was directly labeled with NK cells. Upon cell death, the excessive ROS generation occurred within NK cells, along with IR786s degradation, turning on NIR‐II fluorescent signal at 1550 nm of DCNP under 808‐nm excitation, while the fluorescent signal at 1550 nm of DCNP under 980‐nm excitation was stable. Such an intracellular ROS‐induced ratiometric NIR‐II fluorescent signal was validated to correlate well with NK cell viability in vivo. Using this nanoreporter, we further demonstrated that co‐treatment with IL‐2, IL‐15, and IL‐21 could improve NK cell viability in vivo, achieving enhanced immunotherapy for orthotopic hepatocellular carcinoma. Overall, this strategy allows for longitudinal and quantitative tracking of NK cell viability in NK cell‐based immunotherapy.

In Vivo Tracking of Cell Viability for Adoptive Natural Killer Cell-Based Immunotherapy by Ratiometric NIR-II Fluorescence Imaging.

The therapeutic efficacy of natural killer (NK) cells-based immunotherapy is greatly related with the survival of transplanted NK cells. However, no effective strategy was reported to monitor NK cell viability in adoptive immunotherapy in vivo. Herein, we develop a ratiometric NIR-II fluorescence imaging strategy to quantitively track and visualize the adoptive NK cell viability in vivo in real-time. The nanoprobe consists of lanthanide-based down-conversion nanoparticles (DCNP) coated with IR786s, a reactive oxygen species (ROS) sensitive to NIR dye, which was directly labeled with NK cells. Upon cell death, the excessive ROS generation occurred within NK cells, along with IR786s degradation, turning on NIR-II fluorescent signal at 1550 nm of DCNP under 808-nm excitation, while the fluorescent signal at 1550 nm of DCNP under 980-nm excitation was stable. Such an intracellular ROS-induced ratiometric NIR-II fluorescent signal was validated to correlate well with NK cell viability in vivo. Using this nanoreporter, we further demonstrated that co-treatment with IL-2, IL-15, and IL-21 could improve NK cell viability in vivo, achieving enhanced immunotherapy for orthotopic hepatocellular carcinoma. Overall, this strategy allows for longitudinal and quantitative tracking of NK cell viability in NK cell-based immunotherapy.

Progress in Light‐Responsive Lanthanide Nanoparticles toward Deep Tumor Theranostics

AbstractRecently, lanthanide nanoparticles have aroused widespread interest in cancer theranostics by virtue of their excellent photoresponsive performance in deep‐seated tumors. The abundant ladder‐like energy levels, controllable emission profiles, and unique photoluminescence properties make lanthanide nanoparticles highly efficient for deep skin‐penetration of near‐infrared (NIR) light, concentrating light energy in tumors with negligible scattering and minimal autofluorescence from biological tissues. High‐Z radio‐sensitization of lanthanide elements endows lanthanide nanoparticles with a high X‐ray attenuation coefficient, making them effective nanoprobes for X‐ray‐excited bioimaging and synchronous radiotherapy‐related treatments. In this review, comprehensive progressions including the synthesis, structural characteristics of lanthanide nanoparticles, and distinct optical excitation mechanisms with NIR and X‐ray triggers, are summarized. Advances in NIR‐excited and X‐ray‐triggered cancer imaging methods and therapies are described in detail, wherein NIR‐induced luminescence from upconversion nanoparticles and downconversion nanoparticles are introduced separately based on some typical sensitization. Finally, the challenges and opportunities of lanthanide nanoparticles as light‐triggered cancer theranostic candidates are discussed, whose translation from bench to bedside still has a long journey to go.

Dye‐Sensitized Downconversion Nanoprobes with Emission Beyond 1500 nm for Ratiometric Visualization of Cancer Redox State

AbstractDetection of glutathione (GSH) in the body is essential to accurately map the redox state of cells and real‐time visualization of physiological and pathological conditions in vivo. However, traditional fluorescence (FL) imaging in the near‐infrared I region (NIR‐I, 650–900 nm) is difficult to quantitively visualize GSH in vivo due to the tissue autofluorescence background and disastrous photon scattering. Herein, a NIR‐IIb (1500–1700 nm) nanoprobe consisting of 4‐nitrophenol‐Cy7 (NPh) conjugated lanthanide‐based downconversion nanoparticles (DCNP@NPh‐PEG) is developed for in vivo ratiometric imaging of GSH. In the presence of GSH, NPh shows responsively enhanced FL emission at 808 nm, thus enhancing FL signal at 1550 nm of DCNPs excited by 808 nm (F1550, 808Ex) through non‐radiative energy transfer (NRET) effect, while the fluorescence of DCNP at 1550 nm excited by 980 nm laser (F1550, 980Ex) is stable because no NRET occurred. The ratiometric F1550, 980Ex/F1550, 808Ex value exhibits a linearship with GSH concentration ranged from 0–24 mm with detection limit of 0.3 mm. The NIR‐IIb nanoprobe has excellent performance in detecting and imaging GSH in both subcutaneous tumor and orthotopic colon tumor in vivo with high accuracy and resolution. The design strategy of the ratiometric NIR‐II FL nanoprobe based on the activated FERT effect provides a reliable tool for the development of NIR‐II nanoprobes for accurate biosensing in vivo.

Effect of SrF2:Pr3+-Yb3+ Nanophosphor on Downconversion of High Energy Photons for Efficient Dye-Sensitized Solar Cells

An emerging important class of photovoltaics for the next generation, the dye sensitized solar cells (DSSCs) has attracted great attention due to its low-cost, simple fabrication process and good performance. Though, one of the major loss mechanisms leads to lowering the power energy conversion efficiency is thermalization of charge carriers generated by the absorption of high energy photons. One promising novel strategy to decrease such thermalization loss is the use of downconversion (DC) luminescent materials as spectral converters. The rare-earth doped downshifting materials can converts higher energy photons into lower energy photons based on energy transfer from lanthanide ions to Yb3+ ions. In addition, the downconversion nanoparticles (DCNPs) are also act as scattering centers which can facilitates the light capture in photo-absorbing layer. With this aim, the rare earth doped downconversion SrF2: Pr3+-Yb3+ nanoparticles were synthesized by facile template free hydrothermal method. X-ray diffraction analysis confirms the formation cubic SrF2 phase. The prepared SrF2: Pr3+-Yb3+ down-shifting nanophosphor shows strong absorption in UV region and broad luminescence band emission in visible region evidenced from absorption and photoluminescence studies respectively. The enhancement in power conversion efficiency (PCE) was achieved by employing the synthesized downconverting nanomaterial as bottom layer in DSSC photoanode (Fig.1). The photovoltaic performance of the device was studied using standard solar simulator at 1 Sun intensity (AM 1.5 G) and DSSC with SrF2: Pr3+-Yb3+ shows improved efficiency of 9.066% than bare TiO2 based device (8.395%). The down-shifting nanophosphor material enhanced the efficiency of DSSC by 7.4% with 7.5% increment in photocurrent density compared to bare TiO2 based device. Figure 1

Dual activated NIR-II fluorescence and photoacoustic imaging-guided cancer chemo-radiotherapy using hybrid plasmonic-fluorescent assemblies

Multimodal imaging in the second near-infrared window (NIR-II) guided cancer therapy is a highly precise and efficient cancer theranostic strategy. However, it is still a challenge to develop activated NIR-II optical imaging and therapy agents. In this study, we develop a pH-responsive hybrid plasmonic-fluorescent vesicle by self-assembly of amphiphilic plasmonic nanogapped gold nanorod (AuNNR) and fluorescent down-conversion nanoparticles (DCNP) (AuNNR-DCNP Ve), showing remarkable and activated NIR-II fluorescence (FL)/NIR-II photoacoustic (PA) imaging performances. The hybrid vesicle also exhibited superior loading capacity of doxorubicin as a superior drug carrier and efficient radiosensitizer for X-ray-induced radiotherapy. Interestingly, the accumulated hybrid AuNNR-DCNP Ve in the tumor resulted in a recovery of NIR-II FL imaging signal and a variation in NIR-II PA imaging signal. Dual activated NIR-II PA and FL imaging of the hybrid vesicle could trace drug release and precisely guided cancer radiotherapy to ultimately reduce the side effects to healthy tissue.

Engineering NIR-IIb fluorescence of Er-based lanthanide nanoparticles for through-skull targeted imaging and imaging-guided surgery of orthotopic glioma

Highly sensitive and specific discrimination of brain tumor margins from the surrounding parenchyma remains a formidable challenge. Limited by the short of photostable probes with deep tissue penetration and high efficiency of crossing the blood-brain-barrier (BBB), the development of fluorescence-guided surgery (FGS) of brain tumors was markedly constrained. Herein, we report the capability of the strong second near-infrared-IIb (NIR IIb, 1500−1700 nm) fluorescence from Er-based lanthanide nanoparticles in imaging-guided surgery of orthotopic glioma. We designed an energy-cascaded Er3+-Ce3+-A3+ (A = Yb, Ho, Tm) system and prepared a series of NaErF4:[email protected]4@NaLuF4 down-conversion nanoparticles (DCNPs) for optimizing the influence of NaAF4 interlayer and Ce3+ dopants. We modified the optimal NaErF4:2.5 %[email protected]4(0.9 nm)@NaLuF4 DCNPs with Dye-brush polymer (Dye-BP) to facilitate 4I13/2→4I15/2 transition, which leads to an impressive 675-fold enhancement of 1525 nm fluorescence in aqueous solution under 808 nm excitation due to the excellent energy-cascaded downconversion (ECD), in comparison with that of NaErF4 nanoparticles. We further modified these highly bright nanoparticles with tumor-targeting angiopep-2 peptide, and efficiently delivered them to the glioma by using the focused ultrasound sonication (FUS) to temporarily open the BBB. We obtained the highest tumor-to-background ratio (TBR = 12.5) ever reported in the targeted NIR IIb fluorescence imaging of small orthotopic glioma (size < 3 mm, depth> 3 mm) through intact skull and scalp, which was drastically improved to ∼150 after cardiac perfusion and craniotomy to ensure the precise resection of tumor. More importantly, the size of glioma measured from the width of fluorescence profile is very close to that from T2-weighted MRI images. Our work provides the insights into engineering NIR IIb fluorescence of lanthanide nanoparticles, and demonstrates the great potential of NIR IIb fluorescence imaging-guided surgery of tumor.