Near-Infrared Dual-Modal Sensing of Force and Temperature in Total Knee Replacement Using Mechanoluminescent Phosphor of Sr3Sn2O7: Nd, Yb.

Knee replacement surgery confronts challenges including patient dissatisfaction and the necessity for secondary procedures. A key requirement lies in dual-modal measurement of force and temperature of artificial joints during postoperative monitoring. Here, a novel non-toxic near-infrared (NIR) phosphor Sr3Sn2O7:Nd, Yb, is designed to realize the dual-modal measurement. The strategy is to entail phonon-assisted upconversion luminescence (UCL) and trap-controlled mechanoluminescence (ML) in a single phosphor well within the NIR biological transmission window. The phosphor is embedded in medical bone cement forming a smart joint in total knee replacements illustrated as a proof-of-concept. The sensing device can be charged in vitro by a commercial X-ray source with a safe dose rate for ML, and excited by a low power 980 nm laser for UCL. It attains impressive force and temperature sensing capabilities, exhibiting a force resolution of 0.5% per 10 N, force detection threshold of 15 N, and a relative temperature sensitive of up to 1.3% K-1 at 309 K. The stability against humidity and thermal shock together with the robustness of the device are attested. This work introduces a novel methodological paradigm, paving the way for innovative research to enhance the functionality of artificial tissues and joints in living organisms.

Near-Infrared Emissive Lanthanide Metal-Organic Frameworks for Targeted Biological Imaging and pH-Controlled Chemotherapy.

Near-infrared window II (NIR-II, 1000-1700 nm) imaging displays the advantages in deep-tissue high-contrast imaging in vivo on the strength of the high temporal-spatial resolution and deeper penetration. However, the clinical utility of NIR-II imaging agents is limited by their single function. Herein, for the first time, we report the design of a multifunctional drug delivery system (DDS) assembly, CQ/Nd-MOF@HA nanohybrids, with NIR-II fluorescence (1067 nm), large Stokes shifts, and ultrahigh quantum yield, which combined targeted NIR-II luminescence bioimaging and pH-controlled drug delivery. The nanoscale metal-organic framework (MOF) as a highly promising multifunctional DDS for targeted NIR-II bioimaging and chemotherapy in vitro and in vivo lays the foundation of the MOF-based DDS for further clinical diagnosis and treatment.

Antifungal Activity of a Neodymium-Doped Yttrium Aluminum Garnet 1,064-Nanometer Laser against Sporothrix globosa by Inducing Apoptosis and Pyroptosis via the NLRP3/Caspase-1 Signaling Pathway: In Vitro and In Vivo Study.

Sporotrichosis is a deep fungal infection caused by Sporothrix species. Currently, itraconazole is the main treatment, but fungal resistance, adverse effects, and drug interactions remain major concerns, especially in patients with immune dysfunction. Therefore, an alternative treatment is greatly in demand. This animal study aimed to investigate the inhibitory effect of neodymium-doped yttrium aluminum garnet (Nd:YAG) 1,064-nm laser treatment on Sporothrix globosa and to explore whether it happens through regulation of the Nod-like receptor thermoprotein domain-related protein 3 (NLRP3)/caspase-1 pyroptosis and apoptosis pathway. After laser irradiation, a series of studies, including assays of viability (using the cell counting kit-8 [CCK-8]), morphological structure changes, reactive oxygen species (ROS) accumulation, mitochondrial membrane potential, oxidative stress, cell cycle progression, and metacaspase activation, were conducted to estimate the effect of Nd:YAG 1,064-nm laser treatment on Sporothrix globosa cell apoptosis in vitro. For in vivo studies, mice were infected with S. globosa and then treated with laser or itraconazole, and their footpad skin lesions and the changes in the histology of tissue samples were compared. In addition, changes in the levels of NLRP3, caspase-1, and caspase-3 were assessed by immunohistochemistry, while the levels of interleukin 17 (IL-17), interferon gamma (IFN-γ), and transforming growth factor ß1 (TGF-ß1) in peripheral blood were tested by enzyme-linked immunosorbent assay (ELISA). The in vitro growth of S. globosa was inhibited and apoptosis was observed after laser treatment. According to the in vivo studies, the efficacy of the laser treatment was similar to that of itraconazole. Moreover, the NLRP3/caspase-1 pyroptosis pathway was activated, with a Th1/Th17 cell response, and the expression of caspase-3 was also upregulated. Nd:YAG 1,064-nm laser treatment can effectively inhibit the growth of S. globosa by activating fungal apoptosis and pyroptosis through the NLRP3/caspase-1 pathway. Therefore, Nd:YAG 1,064-nm laser irradiation is an alternative for sporotrichosis therapy. IMPORTANCE Nd:YAG 1,064-nm laser irradiation is a useful alternative for the treatment of sporotrichosis, especially in patients with liver dysfunction, pregnant women, and children, for whom the administration of antifungal drugs is not suitable. It may improve the overall treatment effect by shortening the duration of antifungal treatment and reducing tissue inflammation.

Theoretical and Experimental Vibrational Characterization of Biologically Active Nd(III) Complex.

The neodymium(III) complex of orotic acid (HOA) was synthesized and its structure determined by means of analytical and spectral analyses. Detailed vibrational analysis of HOA, sodium salt of HOA, and Nd(III)-OA systems based on both the calculated and experimental spectra confirmed the suggested metal-ligand binding mode. Significant differences in the IR and Raman spectra of the complex were observed as compared to the spectra of the ligand. The calculated vibrational wavenumbers, including IR intensities and Raman scattering activities, for the ligand and its Nd(III) complex were in good agreement with the experimental data. The vibrational analysis performed for the studied species, orotic acid, sodium salt of orotic acid, and its Nd(III) complex helped to explain the vibrational behaviour of the ligand's vibrational modes, sensitive to interaction with Nd(III). In this paper we also report preliminary results about the cytotoxicity of the investigated compounds. The cytotoxic effects of the ligand and its Nd(III) complex were determined using the MTT method on different tumour cell lines. The screening performed revealed that the tested compounds exerted cytotoxic activity upon the evaluated cell lines.

68Ga-Labeled Magnetic-NIR Persistent Luminescent Hybrid Mesoporous Nanoparticles for Multimodal Imaging-Guided Chemotherapy and Photodynamic Therapy.

Featured with a zero-autofluorescence background, superior signal-to-noise ratio, high sensitivity, and deep penetration ability, near-infrared persistent luminescence nanoparticle (NIR-PLNP)-based multimodal nanoprobes show great potential for full-scale noninvasive cancer diagnosis. However, direct synthesis of NIR-PLNP-based multimodal nanoprobes with high drug loading capacity to meet growing cancer theranostic demands remains a challenge. In this work, multifunctional hybrid mesoporous nanoparticles (HMNPs) that integrate NIR-PLNPs (Ga2O3:Cr3+, Nd3+), magnetic nanoparticles (Gd2O3), and radionuclides (68Ga) are designed and constructed via a large-pore (mesoporous silica nanoparticle) MSN-templated strategy. The ingenious composition design endows HMNPs with rechargeable NIR-PL, superior longitudinal relaxivity, and excellent radioactivity, making these versatile nanoparticles available for long-term in vivo NIR-PL imaging, magnetic resonance imaging (MRI), and positron emission tomography (PET) imaging. More importantly, the application of large-pore MSN templates maintains the mesoporous structure of HMNPs, promising excellent drug loading capacity of these nanoparticles. As a proof-of-concept, HMNPs loaded with a high dose of DOX (chemotherapy agent) and Si-Pc (photosensitizer) are rationally designed for chemotherapy and NIR-PL-sensitized photodynamic therapy (PDT), respectively. Studies with mice tumor models demonstrate that the DOX/Si-Pc-loaded HMNPs possess excellent cancer cell killing ability and an outstanding tumor suppression effect without systemic toxicity. This work shows the great potential of HMNPs as an "all-in-one" nanotheranostic tool for multimodal NIR-PL/MR/PET imaging-guided chemotherapy and NIR-PL-sensitized photodynamic cancer therapy and provides an innovative paradigm for the development of NIR-PLNP-based nanoplatforms in cancer theranostic.

Gram-scale synthesis of a neodymium chelate as a spectral CT and second near-infrared window imaging agent for visualizing the gastrointestinal tract in vivo.

The diagnosis of gastrointestinal (GI) tract diseases is frequently performed in the clinic, so it is crucial to develop high-performance contrast agents for real-time and non-invasive imaging examination of the GI tract. Herein, we show a novel method to synthesize a neodymium (Nd) chelate, Nd-diethylenetriaminepentaacetic acid (Nd-DTPA), on a large scale without byproducts for spectral computed tomography (CT) and second near-infrared window imaging of the GI tract in vivo. The Nd-DTPA was simply generated by heating the mixture of Nd2O3 and DTPA in water at 85 °C for 2 h. This dual-modal imaging agent has the advantages of a simple and green synthesis route, no need of purification process, high yield (86.24%), large-scale production capability (>10 g in lab synthesis), good chemical stability and excellent water solubility (≈2 g mL-1). Moreover, the Nd-DTPA emitted strong near-infrared fluorescence at 1308 nm, and exhibited superior X-ray attenuation ability compared to clinical iohexol. The proposed Nd-DTPA can integrate the complementary merits of dual-modal imaging to realize spatial-temporal and highly sensitive imaging of the GI tract in vivo, and accurate diagnosis of the location of intestinal obstruction and monitor its recovery after surgery. The developed highly efficient method for the gram-scale synthesis of Nd-DTPA and the proposed spectral CT and second near-infrared window dual-modal imaging strategy provide a promising route for accurate visualization of the GI tract in vivo.

LncRNA loc105377478 promotes NPs-Nd2O3-induced inflammation in human bronchial epithelial cells through the ADIPOR1/NF-κB axis.

With the wide application of neodymium oxide nanoparticles (NPs-Nd2O3) in various fields, their health hazards have aroused public concern in recent years. However, data regarding the cytotoxicity of NPs-Nd2O3 is limited. In this study, we investigated the function and mechanism of long-chain non-coding RNAs (lncRNAs) in NPs-Nd2O3-induced airway inflammation. Treatment with NPs-Nd2O3 induced an inflammatory response in human bronchial epithelial cells (16HBE) by upregulating the expression of interleukin-6 (IL-6) and interleukin-8 (IL-8). The levels of LDH and intracellular ROS in the cells treated by various doses of NPs-Nd2O3 also increased significantly. After treatment with 10 µg/ml NPs-Nd2O3, RNA microarray and real-time quantitative polymerase chain reaction (qRT-PCR) showed a significant upregulation of lncRNA loc105377478. Functional experiments suggested lncRNA loc105377478 enhanced the expression of IL-6, IL-8 and ROS in NPs-Nd2O3-treated 16HBE cells, and it was further demonstrated that lncRNA loc105377478 promoted the activation of NF-κB by negatively regulating ADIPOR1 expression. Moreover, the expression of IL-6 and IL-8 in NPs-Nd2O3-treated 16HBE cells was regulated by lncRNA loc105377478, which was mediated by the NF-κB signaling pathway. In conclusion, lncRNA loc105377478 promotes NF-κB activation by negatively regulating ADIPOR1 expression, thereby upregulating the expression of IL-6 and IL-8 in 16HBE cells treated with NPs-Nd2O3.

Isolation of exosomes from whole blood by a new microfluidic device: proof of concept application in the diagnosis and monitoring of pancreatic cancer.

BACKGROUND: Exosomes are endocytic-extracellular vesicles with a diameter around 100 nm that play an essential role on the communication between cells. In fact, they have been proposed as candidates for the diagnosis and the monitoring of different pathologies (such as Parkinson, Alzheimer, diabetes, cardiac damage, infection diseases or cancer). RESULTS: In this study, magnetic nanoparticles (Fe3O4NPs) were successfully functionalized with an exosome-binding antibody (anti-CD9) to mediate the magnetic capture in a microdevice. This was carried out under flow in a 1.6 mm (outer diameter) microchannel whose wall was in contact with a set of NdFeB permanent magnets, giving a high magnetic field across the channel diameter that allowed exosome separation with a high yield. To show the usefulness of the method, the direct capture of exosomes from whole blood of patients with pancreatic cancer (PC) was performed, as a proof of concept. The captured exosomes were then subjected to analysis of CA19-9, a protein often used to monitor PC patients. CONCLUSIONS: Here, we describe a new microfluidic device and the procedure for the isolation of exosomes from whole blood, without any need of previous isolation steps, thereby facilitating translation to the clinic. The results show that, for the cases analyzed, the evaluation of CA19-9 in exosomes was highly sensitive, compared to serum samples.

Moving a neodymium magnet promotes the migration of a magnetic tracer and increases the monitoring counts on the skin surface of sentinel lymph nodes in breast cancer.

BACKGROUND: We suspected that moving a small neodymium magnet would promote migration of the magnetic tracer to the sentinel lymph node (SLN). Higher monitoring counts on the skin surface before making an incision help us detect SLNs easily and successfully. The present study evaluated the enhancement of the monitoring count on the skin surface in SLN detection based on the magnet movement in a sentinel lymph node biopsy (SNB) using superparamagnetic iron oxide (SPIO) nanoparticles. METHODS: After induction of general anesthesia, superparamagnetic iron oxide nanoparticles were injected sub-dermally into the subareolar area or peritumorally. The neodymium magnet was moved over the skin from the injection site to the axilla to promote migration of the magnetic tracer without massage. A total of 62 patients were enrolled from February 2018 to November 2018: 13 cases were subjected to magnet movement 20 times (Group A), 8 were subjected to 1-min magnet movement (Group B), 26 were given a short (about 5 min) interval from injection to 1-min magnet movement (Group C), and 15 were given a long (about 25 min) interval before 1-min magnet movement using the magnetometer's head (Group D). In all cases, an SNB was conducted using both the radioisotope (RI) and SPIO methods. The monitoring counts on the skin surface were measured by a handheld magnetometer and compared among the four groups. Changes in the monitoring count by the interval and magnet movement were evaluated. RESULTS: The identification rates of the SPIO and RI methods were 100 and 95.2%, respectively. The mean monitoring counts of Group A, B, C, and D were 2.39 µT, 2.73 µT, 3.15 µT, and 3.92 µT, respectively (p < 0.0001; Kruskal-Wallis test). The monitoring counts were higher with longer magnet movement and with the insertion of an interval. Although there were no relationships between the monitoring count on the skin surface and clinicopathologic factors, magnet movement strongly influenced the monitoring count on the skin surface. CONCLUSION: Moving a small neodymium magnet is effective for promoting migration of a magnetic tracer and increasing monitoring counts on the skin surface. TRIAL REGISTRATION: UMIN, UMIN000029475. Registered 9 October 2017.

Optimising FRET-efficiency of Nd3+-sensitised upconversion nanocomposites by shortening the emitter-photosensitizer distance.

Nd3+-Sensitised luminescent upconversion nanoparticles (UCNPs) have gained interest recently as theranostics due to their near-infrared (NIR) light excitation with a better tissue penetration depth. One example is the core/shell design NaYF4:Yb,Er@Nd,Yb. When harvesting the upconversion energy in such architectures, the long emitter-photosensitizer (i.e. Er3+-PS) distances lead to inefficient Förster resonance energy transfer (FRET). Herein, we report a new nanocomposite NaYF4:Nd,Yb@Yb@Yb,Er@Y with Nd3+ ions in the core and Er3+ ions in the shell to shorten the Er-PS distance to achieve better FRET. Furthermore, an outer non-emitting protective Y3+ shell and a conducting Yb3+ shell reduced surface quenching and Er3+-to-Nd3+ energy back transfer effects, respectively. The upconversion FRET and downshifting emission efficiencies were simultaneously optimised by adjusting the thickness of the Y3+ shell, and the FRET efficiency was at least 3.7 times that of the reference NaYF4:Yb,Er@Yb@Nd,Yb@Y in a photodynamic therapy (PDT) model.

Molecular Antenna-Sensitized Upconversion Nanoparticle for Temperature Monitored Precision Photothermal Therapy.

BACKGROUND: Photothermal therapy with accurate and real-time temperature detection is desired in clinic. Upconversion nanocrystals (UCNs) are candidate materials for simultaneous temperature detection and photothermal agents carrying. However, the weak luminescence and multiple laser excitations of UCNs limit their application in thermal therapy. MATERIALS AND METHODS: NaYF4:Yb3+,Er3+,Nd3+, PL-PEG-NH2, IR-806 and folic acid are selected as structural components. A nanoprobe (NP) integrated with efficient photothermal conversion and sensitive temperature detection capabilities is synthesized for precise photothermal therapy. The probes are based on near-infrared upconversion nanocrystals doped with Yb, Er and Nd ions, which can be excited by 808 nm light. IR-806 dye molecules are modified on the surface as molecular antennas to strongly absorb near-infrared photons for energy transfer and conversion. RESULTS: The results show that under an 808 nm laser irradiation upconversion luminescence of the nanocrystals is enhanced based on both the Nd ion absorption and the FRET energy transfer of IR-806. The luminescence ratio at 520 and 545 nm is calculated to accurately monitor the temperature of the nanoparticles. The temperature of the nanoprobes increases significantly through energy conversion of the molecular antennas. The nanoparticles are found successfully distributed to tumor cells and tumor tissue due to the modification of the biocompatible molecules on the surface. Tumor cells can be killed efficiently based on the photothermal effect of the NPs. Under the laser irradiation, temperature at mouse tumor site increases significantly, tissue necrosis and tumor cell death can be observed. CONCLUSION: Precision photothermal therapy can thus be achieved by highly efficient near-infrared light absorption and accurate temperature monitoring, making it promising for tumor treatment, as well as the biological microzone temperature detection.

The bioeffects of degradable products derived from a biodegradable Mg-based alloy in macrophages via heterophagy.

Biodegradable magnesium alloys are promising candidates for use in biomedical applications. However, degradable particles (DPs) derived from Mg-based alloys have been observed in tissue in proximity to sites of implantation, which might result in unexpected effects. Although previous in vitro studies have found that macrophages can take up DPs, little is known about the potential phagocytic pathway and the mechanism that processes DPs in cells. Additionally, it is necessary to estimate the potential bioeffects of DPs on macrophages. Thus, in this study, DPs were generated from a Mg-2.1Nd-0.2Zn-0.5Zr alloy (JDBM) by an electrochemical method, and then macrophages were incubated with the DPs to reveal the potential impact. The results showed that the cell viability of macrophages decreased in a concentration-dependent manner in the presence of DPs due to effects of an apoptotic pathway. However, the DPs were phagocytosed into the cytoplasm of macrophages and further degraded in phagolysosomes, which comprised lysosomes and phagosomes, by heterophagy instead of autophagy. Furthermore, several pro-inflammatory cytokines in macrophages were upregulated by DPs through the induction of reactive oxygen species (ROS) production. To the best of our knowledge, this is the first study to show that DPs derived from a Mg-based alloy are consistently degraded in phagolysosomes after phagocytosis by macrophages via heterophagy, which results in an inflammatory response owing to ROS overproduction. Thus, our research has increased the knowledge of the metabolism of biodegradable Mg metal, which will contribute to an understanding of the health effects of biodegradable magnesium metal implants used for tissue repair. STATEMENT OF SIGNIFICANCE: Biomedical degradable Mg-based alloys have great promise in applied medicine. Although previous studies have found that macrophages can uptake degradable particles (DPs) in vitro and observed in the sites of implantation in vivoin vivo, few studies have been carried out on the potential bioeffects relationship between DPs and macrophages. In this study, we analyzed the bioeffects of DPs derived from a Mg-based alloy on the macrophages. We illustrated that the DPs were size-dependently engulfed by macrophages via heterophagy and further degraded in the phagolysosome rather than autophagosome. Furthermore, DPs were able to induce a slight inflammatory response in macrophages by inducing ROS production. Thus, our research enhances the knowledge of the interaction between DPs of Mg-based alloy and cells, and offers a new perspective regarding the use of biodegradable alloys.

Optically active neodymium hydroxide surface-functionalized mesoporous silica micro-cocoons for biomedical applications.

Neodymium hydroxide (Nd(OH)3)-surface modified mesoporous silica micro-cocoon microstructures were prepared using a facile single-step sol-gel chemical process. XRD revealed the semi-crystalline nature of the as-prepared materials. TEM and SEM micrographs exhibited highly monodisperse, non-aggregated, typical ordered mesoporous, and irregular sized cocoon-shaped micro-structures with a narrow size distribution. Optical properties, that were examined in the aqueous media, revealed a high colloidal stability and the formation of a semi-transparent colloidal solution. The colloidal solution of Nd(OH)3-surface functionalized micro-structures revealed well characteristics absorption bands of Nd3+ ions in the visible region. thus validating the successful coating of SiO2@Nd(OH)3 layer over the surface silica forming core-shell structures. Zeta potential, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium) bromide, and neutral red uptake assays were applied in a dose-dependent manner to investigate the biocompatibility and toxic potential of the designed cocoon-shaped microstructures. Both the assays and the high zeta potential value demonstrated good cell viability even at high concentrations and hydrophilic conditions, indicating excellent biocompatibility and non-toxicity. These highly hydrophilic, optically active, mesoporous, biocompatible, and non-toxic cocoon-shaped microstructures could be potentially suitable candidates for optical bio-probes and drug delivery applications.

Neodymium as an alternative contrast for uranium in electron microscopy.

Uranyl acetate is the standard contrasting agent in electron microscopy (EM), but it is toxic and radioactive. We reasoned neodymium acetate might substitute uranyl acetate as a contrasting agent, and we find that neodymium acetate indeed can replace uranyl acetate in several routine applications. Since neodymium acetate is not toxic, not radioactive and easy to use, we foresee neodymium will replace uranyl in many EM sample preparation applications worldwide.

Evaluation of combined treatment with long-pulsed neodymium-doped yttrium aluminum garnet laser and potassium hydroxide for the treatment of recalcitrant wart: a prospective comparative study.

Background: Lasers have been used for verruca treatment in recent years with successful results in some types. In addition, peeling processes have been used to enhance penetration in some studies.Objectives: This study aimed to evaluate combined treatment with LP Nd:YAG laser and KoH for the treatment of recalcitrant wart.Methods: This study included 132 lesions from 38 patients. Long-pulsed (LP) Nd:YAG laser was applied to 66 lesions with daily 10% KOH application at night, and the remaining 66 lesions underwent LP Nd:YAG laser therapy only.Results: Both groups showed statistically significant regressions in the size of the lesions at the end of the fifth session compared with those present at the onset of therapy (p < .05). Also, complete clearance of the lesions was noticed after 2.2 sessions in the combined therapy group, and after 3.1 sessions in the LP Nd:YAG laser group (p < .05).Conclusions: Although the difference in clearance rate between the combined therapy group and the LP Nd:YAG laser group could not be detected after the fifth session, adding KOH to LP Nd:YAG laser can decrease the number of treatment sessions to a large extent.

Nd3+ -Sensitized Upconversion Metal-Organic Frameworks for Mitochondria-Targeted Amplified Photodynamic Therapy.

Herein, we report the design and synthesis of a mitochondria-specific, 808 nm NIR light-activated photodynamic therapy (PDT) system based on the combination of metal-organic frameworks (MOFs) and upconversion photochemistry with an organelle-targeting strategy. The system was synthesized through the growth of a porphyrinic MOF on Nd3+ -sensitized upconversion nanoparticles to achieve Janus nanostructures with further asymmetric functionalization of the surface of the MOF domain. The PDT nanoplatform allows for photosensitizing with 808 nm NIR light, which could effectively avoid the laser-irradiation-induced overheating effect. Furthermore, mitochondria-targeting could amplify PDT efficacy through the depolarization of the mitochondrial membrane and the initiation of intrinsic apoptotic pathway. This work sheds light on the hybrid engineering of MOFs to combat their current limitations for PDT.

Size-Dependent Photothermal Conversion and Photoluminescence of Theranostic NaNdF4 Nanoparticles under Excitation of Different-Wavelength Lasers.

The narrow absorption and emission bands, long fluorescence lifetime, and excellent stability of rare earth nanoparticles (referred to as RE NPs) make them very attractive for multimodal imaging and therapy of cancer. Their narrow absorption requires the careful selection of laser wavelength to achieve the best performance, particularly for RE NPs simultaneously having photothermal and photoluminescent properties (e.g., Nd-based nanoparticles), which has not been investigated. Herein, we prepared a series of different-sized NaNdF4 nanoparticles (referred to as NNF NPs) (i.e., 4.7, 5.9, 12.8, and 15.6 nm) from ultrasmall nanoclusters and investigated their in vitro and in vivo size-dependent photothermal conversion and photoluminescence under irradiation by a 793 nm laser and an 808 nm laser, respectively. We find that all nanoparticles exhibited the better photothermal conversion performance under the irradiation of the 808 nm laser than under the 793 nm laser, of which 12.8 nm NNF NPs showed the best performance, and the temperature of their solution can be quickly increased from 30 °C to around 60 °C within 10 min under the irradiation of the 808 nm laser with a power intensity of 0.75 W/cm2. When we used the 793 nm laser to excite these NNF NPs, we found that all nanoparticles exhibited the stronger photoluminescence in the second near-infrared window (NIR-II) than under the excitation by the 808 nm laser, of which 15.6 nm NNF NPs possessed the strongest NIR-II luminescence. We then modified 12.8 nm NNF NPs with phospholipid carboxyl PEG and functionalized with RGD for actively targeted imaging of cancer. The NaNdF4@PEG@RGD nanoparticles (referred to as NNF-P-R NPs) have good biocompatibility, stability, and excellent targeting capability. The in vivo result show that 12.8 nm NNF NPs exhibited better photothermal conversion performance under the irradiation of the 808 nm laser, and stronger NIR-II fluorescence under irradiation of the 793 nm laser, which are consistent with the in vitro result. This work demonstrates the significance of selection of the proper laser wavelength for maximally taking advantage of RE nanoparticles for the diagnosis and treatment of cancer.

Prussian blue-coated lanthanide-doped core/shell/shell nanocrystals for NIR-II image-guided photothermal therapy.

Lanthanide-doped nanoparticles have long been stereotyped for optical luminescence bioimaging. However, they are known to be unable to produce therapeutic abilities. Here, we describe a lanthanide-based theranostic agent, namely, prussian blue (PB)-coated NaErF4@NaYF4@NaNdF4 core/shell/shell nanocrystals encapsulated in a phospholipid PEG micelle (PEG-CSS@PB), which showed switched imaging and hyperthermia abilities under distinct near infrared (NIR) light activation. The erbium (Er3+)-enriched inner core nanocrystals (NaErF4) enabled the emission of tissue-penetrating luminescence (1525 nm) in the second biological window (NIR-II, 1000-1700 nm), which endowed high-resolution optical imaging of the blood vessels and tumors under ∼980 nm excitation. High neodymium (Nd3+) concentrations in the epitaxial outer NaNdF4 shell introduced maximum cross relaxation processes that converted the absorbed NIR light (∼808 nm) into heat at high efficiencies, thus providing abilities for photothermal therapy (PTT). Importantly, the coated Prussian blue (PB) increased light absorption by about 10-fold compared to the composite free of PB, thus entailing a high light-to-heat conversion efficiency of ∼50.5%. This commensurated with that of well-established gold nanorods. As a result, the PEG-CSS@PB nanoparticles with MTT-determined low toxicities resulted in ∼80% death of HeLa cells at a dose of 600 µg mL-1 under 808 nm laser irradiance (1 W cm-2) for 10 min. Moreover, utilizing the same light dose, a single PTT treatment in tumor-bearing BALB/c mice shrunk the tumor size by ∼12-fold compared to the tumors without treatment. Our results, here, constituted a solid step forward to entitle lanthanide-based nanoparticles as theranostic agents in nanomedicine studies.

Upconversion System with Quantum Dots as Sensitizer: Improved Photoluminescence and PDT Efficiency.

Upconversion nanoparticles (UCNPs) are prospective platforms for bioimaging and phototherapy, but a critical bottleneck is the limited brightness due to the faint absorptivity of lanthanide ions and the low quantum yield. To circumvent this problem, we herein propose our strategy to reconstruct the energy cascade of UCNPs using semiconductor quantum dots (QDs) as light sensitizer of Nd3+/Yb3+ codoped UCNPs. Ag2Se QDs with strong absorption at 808 nm acted as efficient antenna and transferred their energy to Yb3+ via a resonance energy transfer process, significantly enhancing the luminescence of UCNPs. This nanocomposite was then combined with Rose Bengal and applied for photodynamic therapy. Both in vitro and in vivo studies revealed the introduction of QDs improved the therapeutic performance remarkably. Our study suggests Ag2Se QDs with excellent photophysical properties can be promising agents to overcome the shortcomings of UCNPs and further strengthen their applications.