Upconversion Luminescence Imaging Research Articles

NIR Light and GSH Dual-Responsive Upconversion Nanoparticles Loaded with Multifunctional Platinum(IV) Prodrug and RGD Peptide for Precise Cancer Therapy.

Platinum(II) drugs as a first-line anticancer reagent are limited by side effects and drug resistance. Stimuli-responsive nanosystems hold promise for precise spatiotemporal manipulation of drug delivery, with the aim to promote bioavailability and minimize side effects. Herein, a multitargeting octahedral platinum(IV) prodrug with octadecyl aliphatic chain and histone deacetylase inhibitor (phenylbutyric acid, PHB) at axial positions to improve the therapeutic effect of cisplatin was loaded on the upconversion nanoparticles (UCNPs) through hydrophobic interaction. Followed attachment of DSPE-PEG2000 and arginine-glycine-aspartic (RGD) peptide endowed the nanovehicles with high biocompatibility and tumor specificity. The fabricated nanoparticles (UCNP/Pt(IV)-RGD) can be triggered by upconversion luminescence (UCL) irradiation and glutathione (GSH) reduction to controllably release Pt(II) species and PHB, inducing profound cytotoxicity. Both in vitro and in vivo experiments demonstrated that UCNP/Pt(IV)-RGD exhibited remarkable antitumor efficiency, high tumor-targeting specificity, and real-time UCL imaging capacity, presenting an intelligent platinum(IV) prodrug-loaded nanovehicle for UCL-guided dual-stimuli-responsive combination therapy.

Ultrasensitive upconverting nanoprobes for in situ imaging of drug-induced liver injury using miR-122 as the biomarker

Drug-induced liver injury (DILI) is a frequent adverse drug reaction. The current clinical diagnostic methods are inadequate for accurate and early detection of DILI due to the lack of effective diagnostic biomarkers. Hepatocyte-specific miR-122 is released from injured hepatocytes promptly and its efflux is significantly correlated with the progression of DILI. Therefore, achieving precise in situ detection of miR-122 with high sensitivity is vital for early visualization of DILI. Herein, a new nanoprobe, consisting of miR-122 aptamer, upconversion nanoparticles (UCNPs) and Prussian blue nanoparticles (PBNPs) was introduced for the early and sensitive detection of DILI in situ. As the nanoprobes reached in the liver, miR-122 aptamer-based entropy-driven strand displacement (ESDR) signal amplification reaction was triggered and luminescence resonance energy transfer (LRET) between UCNPs and PBNPs was responded to achieve the high-fidelity detection of DILI. A negative correlation was observed between the intensity of upconversion luminescence (UCL) and the concentration of miR-122. UCL imaging conducted both in vivo and ex vivo indicated that a reduction in miR-122 concentration led to an increase in UCL intensity, revealing a precise state of DILI. The detection technique demonstrated a positive correlation between signal intensity and severity, offering a more straightforward and intuitive method of visualizing DILI.

Switching between upconversion luminescence imaging and therapy in vitro enabled by NIR excitation modulation of nanocomposites

We synthesized a theranostics-integrated nanocomposite capable of switching between upconversion luminescence imaging and photothermal therapy/photodynamic therapy/NO gas therapy by changing the wavelength of near-infrared light irradiation.

Tumor Microenvironment-Specific Driven Nanoagents for Synergistic Mitochondria Damage-Related Immunogenic Cell Death and Alleviated Immunosuppression.

Despite significant breakthroughs in immunotherapy, the limitations of inadequate immune stimulation and stubborn immune resistance continue to present opportunities and challenges. Therefore, a two-pronged approach, encompassing the activation of immunogenic cell death (ICD) and blocking the indoleamine 2,3-dioxygenase (IDO)-mediated pathway, is devised to elicit systemic anti-tumor immunity and alleviate immunosuppression. Herein, a tumor microenvironment (TME)-specific driven nanoagent is composedof a tetrasulfide bond-bridged mesoporous silica layer (MON) coated up-conversion nanoparticles as a nano-carrier, combines Fe2+, curcumin, and indoximod for operating chemodynamic therapy/chemotherapy/immunotherapy. The consumption of glutathione (GSH) caused by MON degradation, the Fenton reaction of Fe2+, and curcumin triggering mitochondrial damage collectively exacerbate the oxidative stress, leading to a violent immunoreaction and reversal of the immunosuppressive TME through a combination of IDO-inhibitors. Meanwhile, upconversion luminescence (UCL) imaging serves as a significant guiding tool for drug delivery and the treatment of nanoagents. In vivo and in vitro experiment results demonstrate that the nanosystem not only effectively inhibits the growth of primary tumors but also induces immune priming and memory effects to reject re-challenged tumors. The strategy as a complementary approach displays great potential for future immunotherapy along with other multimodal treatment modes.

Simultaneous Imaging and Photodynamic-Enhanced Photothermal Inhibition of Cancer Cells Using a Multifunctional System Combining Indocyanine Green and Polydopamine-Preloaded Upconversion Luminescent Nanoparticles.

This work introduces a novel multifunctional system called UPIPF (upconversion-polydopamine-indocyanine-polyethylene-folic) for upconversion luminescent (UCL) imaging of cancer cells using near-infrared (NIR) illumination. The system demonstrates efficient inhibition of human hepatoma (HepG2) cancer cells through a combination of NIR-triggered photodynamic therapy (PDT) and enhanced photothermal therapy (PTT). Initially, upconversion nanoparticles (UCNP) are synthesized using a simple thermal decomposition method. To improve their biocompatibility and aqueous dispersibility, polydopamine (PDA) is introduced to the UCNP via a ligand exchange technique. Indocyanine green (ICG) molecules are electrostatically attached to the surface of the UCNP-polydopamine (UCNP@PDAs) complex to enhance the PDT and PTT effects. Moreover, polyethylene glycol (PEG)-modified folic acid (FA) is incorporated into the UCNP-polydopamine-indocyanine-green (UCNP@PDA-ICGs) nanoparticles to enhance their targeting capability against cancer cells. The excellent UCL properties of these UCNP enable the final UCNP@PDA-ICG-PEG-FA nanoparticles (referred to as UPIPF) to serve as a potential candidate for efficient anticancer drug delivery, real-time imaging, and early diagnosis of cancer cells. Furthermore, the UPIPF system exhibits PDT-assisted PTT effects, providing a convenient approach for efficient cancer cell inhibition (more than 99% of cells are killed). The prepared UPIPF system shows promise for early diagnosis and simultaneous treatment of malignant cancers.

A "Chase and Block" Strategy for Enhanced Cancer Therapy with Hypoxia-Promoted Photodynamic Therapy and Autophagy Inhibition Based on Upconversion Nanocomposites.

The combination of hypoxia-promoted photodynamic therapy (PDT) and autophagy modulation has shown strong potential in the treatment of hypoxic tumors. Here, a novel design is put forward for synergistic PDT and autophagy inhibition to amplify the effect of cancer therapy by a "chase and block" strategy. Specifically, the organic photosensitive molecule (denoted FL) is encapsulated in a hydrophobic layer between multi-band emitted upconversion nanoparticles (UCNPs) and the amphiphilic polymer DSPE-PEG-COOH, allowing FL to fully exploit the luminescence spectrum of UCNPs under near-infrared (NIR) light irradiation. The FL is specifically activated by nitroreductase in the tumor microenvironment (TME), enabling hypoxia-promoted PDT and thus performing a "chase" strategy for cancer therapy. Additionally, the nanosystem is combined with an autophagy-inhibiting melittin pro-peptide (denoted as MEL), which could be triggered by the highly expressed legumain in tumor cells to inhibit the autophagy procedure by disrupting the lysosomal membrane, thus "blocking" the cancer cells from rescuing themselves and amplifying the killing effect of PDT. Both FL and MEL can be specifically activated by TME and the upconversion luminescence imaging of UCNPs offers a tracer function for the treatment. Therefore, UCNPs@FL-MEL might be an important reference for the design and development of future nanotherapeutic agents.

Near‐Infrared Light Triggered Intelligent Nanoplatform for Synergistic Chemo‐Photodynamic Therapy of Tumor

AbstractChemo‐photodynamic therapy nanodelivery systems provide a potential strategy to enhance anticancer effect. However, the treatment efficiency of stimuli‐responsive nanotheranostics remains a challenge owing to off‐target properties, poor tissue penetration, and slow drugs release. Herein, di‐selenide‐bridged mesoporous silica (Se‐Se‐mSiO2) is introduced into a near‐infrared (NIR) light triggered and tumor microenvironment (TME)‐activated intelligent nanoplatform (UCNPs@mSiO2‐Ce6@Se‐Se‐mSiO2(DOX)@HA (UCSSDH)) realizing burst drug release on demand. Typically, the UCSSDH actively targets cancer cells and accumulates in tumor site through hyaluronic acid (HA). Then, under the irradiation of 980 nm NIR light, the upconverted 650 nm emission light activates photosensitizer Ce6 to produce the singlet oxygen (1O2) for photodynamic therapy (PDT). More importantly, 1O2 further cleaves di‐selenide bonds which are sensitive to reactive oxygen species (ROS), driving the rapid degradation of Se‐Se‐mSiO2 accompanied by the burst release of doxorubicin (DOX). Consequently, UCSSDH achieves efficient chemo‐photodynamic therapy of tumors. Last but not least, the upconversion nanoparticles (UCNPs) perform upconversion luminescence (UCL) imaging to monitor the drugs delivery. Collectively, an intelligent drug delivery system integrating therapeutic, monitoring, and targeting is exploited for NIR light‐triggered synergistic tumor therapy. This study broadens fresh vision into the development of controlled drug release and provides a momentous thought for potential clinical cancer therapy.

Upconversion nanoparticle platform for efficient dendritic cell antigen delivery and simultaneous tracking

Upconversion nanoparticles (UCNPs) represent a group of NPs that can convert near-infrared (NIR) light into ultraviolet and visible light, thus possess deep tissue penetration power with less background fluorescence noise interference, and do not induce damage to biological tissues. Due to their unique optical properties and possibility for surface modification, UCNPs can be exploited for concomitant antigen delivery into dendritic cells (DCs) and monitoring by molecular imaging. In this study, we focus on the development of a nano-delivery platform targeting DCs for immunotherapy and simultaneous imaging. OVA 254–267 (OVA24) peptide antigen, harboring a CD8 T cell epitope, and Pam3CysSerLys4 (Pam3CSK4) adjuvant were chemically linked to the surface of UCNPs by amide condensation to stimulate DC maturation and antigen presentation. The OVA24-Pam3CSK4-UCNPs were thoroughly characterized and showed a homogeneous morphology and surface electronegativity, which promoted a good dispersion of the NPs. In vitro experiments demonstrated that OVA24-Pam3CSK4-UCNPs induced a strong immune response, including DC maturation, T cell activation, and proliferation, as well as interferon gamma (IFN-γ) production. In vivo, highly sensitive upconversion luminescence (UCL) imaging of OVA24-Pam3CSK4-UCNPs allowed tracking of UCNPs from the periphery to lymph nodes. In summary, OVA24-Pam3CSK4-UCNPs represent an effective tool for DC-based immunotherapy.Graphical abstract

A Hemicyanine-Assembled Upconversion Nanosystem for NIR-Excited Visualization of Carbon Monoxide Bio-Signaling In Vivo.

Carbon monoxide (CO) is considered as the second gasotransmitter involved in a series of physiological and pathological processes. Although a number of organic fluorescent probes have been developed for imaging CO, these probes display excitation within the ultraviolet or visible range, which restrict their applications in the complex biosystems. In the present work, a strategy is developed to construct an upconversion nanoparticles-based nanosystem for upconversion luminescent (UCL) sensing CO. This nanosystem exhibits a fast response to CO with high sensitivity and selectivity in aqueous solution by a near-infrared-excited ratiometric UCL detection method. Meanwhile, laser scanning upconversion luminescence microscope experiments demonstrate that this nanosystem can visualize the endogenous CO bio-signaling in living cells, deep tissues, zebrafish, and living mice by ratiometric UCL imaging. In particular, this nanosystem has been successfully employed in visualization of the endogenous CO bio-signaling through up-regulation of heme oxygenase-1 (HO-1) in the progression of hypoxia, acute inflammation, or ischemic injury. This work demonstrates that the outstanding performance of the nanosystem not only can provide an effective tool for further understanding the role of CO in the physiological and pathological environment, but also may have great potential ability for tracking the expression of HO-1in living systems.

Dual-modality Imaging of Angiogenesis in Unstable Atherosclerotic Plaques with VEGFR2-Targeted Upconversion Nanoprobes in vivo

AimAngiogenesis plays a major role in atherosclerotic plaque development and instability. Our study aims to develop a novel optical and magnetic resonance (MR) dual-modality molecular imaging probe to early detect unstable plaques in vivo by targeting biomarkers of angiogenesis in murine models of atherosclerosis (AS).MethodsImmunofluorescence and western blot were used to detect the expression of Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) in activated Human Umbilical Vein Endothelial Cells (HUVECs). After synthesis and identification of novel short peptide VRBP1-targeted VEGFR2, HUVECs were co-cultured with FITC-VRBP1 to test specific affinity of VRBP1. Then VRBP1-UCNPstargeting VEGFR2 were constructed by conjugating VRBP1 to the surface of NaGdF4:Yb,Er@NaGdF4 nanoparticles. The characterization of the nanoparticles was performed by transmission electron microscopy (TEM), distribution of size, hydrodynamic size, zeta potential, absorption spectra, emission spectra, imaging intensity of different concentrations, binding affinity and cytotoxicity of nanoprobes in vitro. The upconversion luminescence (UCL) and MR imaging were performed to identify unstable atherosclerotic plaque in ApoE−/− mice in vivo and ex vivo. Morphological staining was used to verify AS model and angiogenesis, and Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES) was used to confirm accumulation of the nanoparticles after imaging.ResultsAfter induced by hypoxia and ox-LDL, the expression of VEGFR2 in activated HUVECs was enhanced. FITC-VRBP1 can specifically bind to the HUVECs. Characterization of the nanoparticles showed that particles size is uniform with a stable structure, specific optical and MR signal, good binding affinity to VEGFR2 and low cytotoxicity. In vivo and ex vivo UCL imaging and quantitative analysis revealed that distinctive optical signal was observed in the regions of left carotid common arteries (LCCAs) of AS group after injection of VRBP1-UCNPs. Higher signal intensity on T1-weighted MR imaging appeared in the LCCA wall of AS group after injection. The results of morphological staining demonstrated angiogenesis in the atherosclerotic plaques, Gd ions in LCCAs, aortic arch and renal arteries bifurcations detected by ICP-AES confirmed accumulation of the nanoparticles in plaque.ConclusionsWe successfully design and synthesize a novel UCNPs using peptide VRBP1 targeting to VEGFR2. In vivo imaging demonstrates that VRBP1-UCNPs can be used to perform optical/MR dual-modality imaging targeting angiogenesis in plaques, which is a promising technique to early detect unstable atherosclerosis.

Novel upconversion fluorescence sensor for the detection and imaging of procyanidins in foods by NaYF4:Yb/Tm@NaYF4:Yb-Cit-CD

In this paper, a β-cyclodextrin (CD)-modified citric acid (Cit)-stabilized blue-emitting upconversion nanocomposite NaYF4:Yb/Tm@NaYF4:Yb-Cit-CD (abbreviated as Y/Yb/Tm@Y/Yb-Cit-CD) has been prepared. Under 980 nm laser excitation, the fluorophore Y/Yb/Tm@Y/Yb of the nanocomposite emits blue fluorescence, and the spectral peak is approximately 482 nm. The emission spectrum partly overlaps with the absorption spectrum of procyanidins, which will lead to the upconversion fluorescence intensity of Y/Yb/Tm@Y/Yb decreasing by the fluorescence resonance energy transfer between Y/Yb/Tm@Y/Yb and procyanidins. Thus, the Y/Yb/Tm@Y/Yb-Cit-CD nanocomposite can be used as an upconversion fluorescence probe to detect procyanidins. The quantitative analysis of procyanidins has displayed a linear range of 0.1–1000 μM, with a detection limit of 0.06718 μM (S/N = 3). Furthermore, this probe has shown potential for detection of procyanidins in biological samples and upconversion luminescence imaging analysis in vivo.

Ferrocene-functionalized core–shell lanthanide-doped upconversion nanoparticles: NIR light promoted chemodynamic therapy and luminescence imaging of solid tumors

In the current study, we successfully prepared core–shell NaYF4:Yb,Tm@NaYF4:Eu upconversion nanoparticles to achieve three intense upconversion emissions, the 476 nm emission can active photo-Fenton reaction to introduce the cancer cell apoptosis, while 647 nm and 696 nm emissions are suitable for the upconversion luminescence (UCL) imaging. Nanosystem Lipo-FNPs was then constructed by loading carboxyl-containing ferrocene derivative Fc onto NaYF4:Yb,Tm@NaYF4:Eu UCNPs surface, then further be encapsulated in liposomes. Lipo-FNPs exhibited obvious 980 nm NIR-promoted cytotoxicity induced by ·OH from photo-Fenton reaction, with IC50 = 22.54 ± 1.93 μg/mL in AGS cancer cells. The oxidation product Fc+NPs of photo-Fenton reaction can be reversibly reduced by GSH, which suggested that FNPs have the potential to disturb the intracellular redox homeostasis. Cell fluorescence confocal experiments and in vivo fluorescence imaging experiments confirmed that this nanosystem can achieve biological UCL imaging from cells to the level of living organisms. Therefore, Lipo-FNPs nanosystem was developed to achieve the integrated missions in solid tumors, NIR promoted effective tumor suppression and bright UCL imaging.

Anchoring Group-Mediated Radiolabeling of Inorganic Nanoparticles─A Universal Method for Constructing Nuclear Medicine Imaging Nanoprobes.

Nuclear medicine imaging has aroused great interest in the design and synthesis of versatile radioactive nanoprobes, while most of the methods developed for radiolabeling nanoprobes are difficult to satisfy the criteria of clinical translation, including easy operation, mild labeling conditions, high efficiency, and high radiolabeling stability. Herein, we demonstrated the universality of a simple but efficient radiolabeling method recently developed for constructing nuclear imaging nanoprobes, that is, ligand anchoring group-mediated radiolabeling (LAGMERAL). In this method, a diphosphonate-polyethylene glycol (DP-PEG) decorating on the surface of inorganic nanoparticles plays an essential role. In principle, owing to the strong binding affinity to a great variety of metal ions, it can not only endow the underlying nanoparticles containing metal ions including some main group metal ions, transition metal ions, and lanthanide metal ions with excellent colloidal stability and biocompatibility but also enable efficient radiolabeling through the diphosphonate group. Based on this assumption, inorganic nanoparticles such as Fe3O4 nanoparticles, NaGdF4:Yb,Tm nanoparticles, and Cu2-xS nanoparticles, as representatives of functional inorganic nanoparticles suitable for different imaging modalities including magnetic resonance imaging (MRI), upconversion luminescence imaging (UCL), and photoacoustic imaging (PAI), respectively, were chosen to be radiolabeled with different kinds of radionuclides such as SPECT nuclides (e.g., 99mTc), PET nuclides (e.g., 68Ga), and therapeutic SPECT nuclides (e.g., 177Lu) to demonstrate the reliability of the LAGMERAL approach. The experimental results showed that the obtained nanoprobes exhibited high radiolabeling stability, and the whole radiolabeling process had negligible impacts on the physical and chemical properties of the initial nanoparticles. Through passive targeting SPECT/MRI of glioma tumor, active targeting SPECT/UCL of colorectal cancer, and SPECT/PAI of lymphatic metastasis, the outstanding potentials of the resulting radioactive nanoprobes for sensitive tumor diagnosis were demonstrated, manifesting the feasibility and efficiency of LAGMERAL.

Dual-Responsive and ROS-Augmented Nanoplatform for Chemo/Photodynamic/Chemodynamic Combination Therapy of Triple Negative Breast Cancer.

Integrating chemodynamic therapy (CDT) and photodynamic therapy (PDT) into one nanoplatform can produce much more reactive oxygen species (ROS) for tumor therapy. Nevertheless, it is still a great challenge to selectively generate sufficient ROS in tumor regions. Meanwhile, CDT and PDT are restricted by insufficient H2O2 content in the tumor as well as by the limited tumor tissue penetration of the light source. In this study, a smart pH/ROS-responsive nanoplatform, Fe2+@UCM-BBD, is rationally designed for tumor combination therapy. The acidic microenvironment can induce the pH-responsive release of doxorubicin (DOX), which can induce tumor apoptosis through DNA damage. Beyond that, DOX can promote the production of H2O2, providing sufficient materials for CDT. Of note, upconversion nanoparticles at the core can convert the 980 nm light to red and green light, which are used to activate Ce6 to produce singlet oxygen (1O2) and achieve upconversion luminescence imaging, respectively. Then, the ROS-responsive linker bis-(alkylthio)alkene is cleaved by 1O2, resulting in the release of Fenton reagent (Fe2+) to realize CDT. Taken together, Fe2+@UCM-BBD exhibits on-demand therapeutic reagent release capability, excellent biocompatibility, and remarkable tumor inhibition ability via synergistic chemo/photodynamic/chemodynamic combination therapy.

Temperature-Feedback Nanoplatform for NIR-II Penta-Modal Imaging-Guided Synergistic Photothermal Therapy and CAR-NK Immunotherapy of Lung Cancer.

In this study, to visually acquire all-round structural and functional information of lung cancer while performing synergistic photothermal therapy (PTT) and tumor-targeting immunotherapy, a theranostic nanoplatform that introduced upconversion nanoparticles (UCNPs) and IR-1048 dye into the lipid-aptamer nanostructrure (UCILA) is constructed. Interestingly, the IR-1048 dye grafted into the lipid bilayer can serve as the theranostic agent for photoacoustic imaging, optical coherence tomography angiography, photothermal imaging, and PTT in the second near infrared (NIR-II) window. In addition, loaded in the inner part of UCILA, UCNPs possess the superior luminescence property and high X-ray attenuation coefficient, which can act as contrast agents for computed tomography (CT) and thermo-sensitive up-conversion luminescence (UCL) imaging, enabling real-time tracking of metabolic activity of tumor and temperature-feedback PTT. Furthermore, under the complementary guidance of penta-modal imaging and an accurate monitoring of in situ temperature change during PTT, UCILA exhibits its excellent capability for ablating the lung tumor with minimal side effects. Meanwhile, synergistic CAR-NK immunotherapy is carried out specifically to eradicate any possible residual tumor cells after PTT. Therefore, the UCILA nanoplatform is demonstrated as a multifunctional theranostic agent for both penta-modal imaging and temperature-feedback PTT while conducting targeting immunotherapy of lung cancer.

Nd3+-sensitized upconversion nanoparticle coated with antimony shell for bioimaging and photothermal therapy in vitro using single laser irradiation

Combining treatment and diagnosis, called theranostics, which is achieved within single nanoparticle is an ultimate goal of many studies. Herein, we developed a new nanotheranostic agent − Nd3+-sensitized upconversion nanoparticles core for dual modal imaging (i.e., upconversion luminescence imaging and magnetic resonance imaging) and antimony nanoshell for photothermal therapy (PTT). The core-shell-shell upconversion nanoparticles (NaYF4:Yb,Er@NaYF4:Yb,Nd@NaGdF4:Nd, named as UCNP) were firstly synthesized using thermal decomposition method and then were coated by antimony shell over the surface of UCNP using simple cost and time effective new method. Furthermore, the surface of UCNP@Sb nanostructures was modified with DSPE-PEG in order to enhance the water solubility and biocompatibility. The final nanotheranostic agent, named as UCNP@Sb-PEG, exhibits very low toxicity, good biocompatibility, very good photothermal therapeutic effect, and efficient upconversion luminescence (UCL) imaging of HeLa cells under only one laser (808 nm) irradiation. The antimony shell is quenching the upconversion emission in pristine nanotheranostic agent, but interestingly, the UCL intensity of the agent recovers progressively under 808 nm laser irradiation due to light induced degradability of antimony shell. Besides, high longitudinal relaxivity (r1) obtained from the experiment approves excellent potential of the nanotheranostic agent for T1-weighted magnetic resonance imaging application.

Nanoparticles: Untying the Gordian Knot in Conventional Computed Tomography Imaging

X-ray computed tomography (CT) imaging plays an essential role in disease diagnosis due to its noninvasive, painless mode and superior penetration depth. However, the resolution of the soft tissue ...

Targeted Luminescent Probes for Precise Upconversion/NIR II Luminescence Diagnosis of Lung Adenocarcinoma.

In this research, the antibody of the searched hub genes has been proposed to combine with a rare-earth composite for an upconversion luminescence (UCL) and downconversion (DCL) NIR-II imaging strategy for the diagnosis of lung adenocarcinoma (LUAD). Weighted gene co-expression network analysis is used to search the most relevant hub genes, and the required top genes that contribute to tumorigenesis (negative: CLEC3B, MFAP4, PECAM1, and FHL1; positive: CCNB2, CDCA5, HMMR, and TOP2A) are identified and validated by survival analysis and transcriptional and translational results. Meanwhile, fluorescence imaging probes (NaYF4:Yb,Er,Eu@NaYF4:Nd, denoted as NYF:Eu NPs) with multimodal optical imaging properties of downconversion and upconversion luminescence in the visible region and luminescence in the near infrared II region are designed with various uniform sizes and enhanced penetration and sensitivity. Finally, when the NYF:Eu NP probe is combined with antibodies of these chosen positive hub genes (such as, TOP2A and CCNB2), the in vitro and in vivo animal experiments (flow cytometry, cell counting kit-8 assay using A549 cells, and in vivo immunohistochemistry IHC microscopy images of LUAD from patient cases) indicate that the designed nanoprobes can be excellently used as a targeted optical probe for future accurate diagnosis and surgery navigation of LUAD in contrast with other cancer cells and normal cells. This strategy of antibodies combined with optical probes provides a dual-modal luminescence imaging method for precise medicine.

Controlled synthesis and upconversion luminescence properties of highly uniform and monodisperse β-NaYF4 :Yb3+ ,Tm3+ nanocrystals.

Ytterbium, thulium (Yb3+ ,Tm3+ ) co-doped β-NaYF4 upconversion nanocrystals (U-NCs) were synthesized by a convenient hydrothermal method using sodium citrate as a capping agent. X-ray diffraction (XRD) analysis revealed that NCs phase structures were dependent on reaction time. Field-emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM) results showed that the morphology of U-NCs could be controlled by adjusting the concentration of sodium citrate added in the hydrothermal reaction. Moreover, the emission spectra of the U-NCs were investigated to evaluate upconversion efficiency. Strong luminescence intensity of the U-NCs was observed after tuned with optimized concentration of sodium citrate. Furthermore, the U-NCs were incubated with MCF-7 cells at 37°C for 24 h. Under irradiation of a 980 nm laser, the upconversion blue emission of the NCs in MCF-7 cells can be clearly observed through a confocal microscope with an upconversion imaging system and high quality upconversion luminescence images can be acquired. Thus, prepared β-NaYF4 :Yb3+ ,Tm3+ NCs provide us with highly efficient luminescent probes which can be applied for diverse bio-applications.

A CORM loaded nanoplatform for single NIR light-activated bioimaging, gas therapy, and photothermal therapy in vitro.

Carbon monoxide (CO) can cause mitochondrial dysfunction, inducing apoptosis of cancer cells, which sheds light on a potential alternative for cancer treatment. However, the existing CO-based compounds are inherently limited by their chemical nature, such as high biological toxicity and uncontrolled CO release. Therefore, a nanoplatform - UmPF - that addresses such pain points is urgently in demand. In this study, we have proposed a nanoplatform irradiated by near-infrared (NIR) light to release CO. Iron pentacarbonyl (Fe(CO)5) was loaded in the mesoporous polydopamine layer that was coated on rare-earth upconverting nanoparticles (UCNPs). The absorption wavelength of Fe(CO)5 overlaps with the emission bands of the UCNPs in the UV-visible light range, and therefore the emissions from the UCNPs can be used to incite Fe(CO)5 to control the release of CO. Besides, the catechol groups, which are abundant in the polydopamine structure, serve as an ideal locating spot to chelate with Fe(CO)5; in the meantime, the mesoporous structure of the polydopamine layer improves the loading efficiency of Fe(CO)5 and reduces its biological toxicity. The photothermal effect (PTT) of the polydopamine layer is highly controllable by adjusting the external laser intensity, irradiation time and the thickness of the polydopamine layer. The results illustrate that the combination of CO gas therapy (GT) and polydopamine PTT brought by the final nanoplatform can be synergistic in killing cancer cells in vitro. More importantly, the possible toxic side effects can be effectively prevented from affecting the organism, since CO will not be released in this system without near-infrared light radiation.