Near-infrared Persistent Luminescence Nanoparticles Research Articles

Trimodality applications validation of near-infrared persistent luminescence nanoparticles

Here, we introduced Cr ion, as emission center, to achieve the NIR emission for MgGa2O4, while Zn ion is used to increase oxygen vacancy to improve the emission intensity. Thus, Mg0.9Zn0.1Ga2O4: 0.006 Cr3+ (MZGC) was prepared as the optimal composite with the enhanced NIR emission at 708 nm, while the host, Mg0.9Zn0.1Ga2O4 (MZG), exhibited the afterglow emission at 425 nm under 224 nm excitation. The result from density functional theory confirmed Cr and Zn ions occupied in the octahedral coordination to improve the optical behaviors. The NIR emission of MZGC was applied for bioimaging as confirmed with mice model under both visible and NIR excitation. We proposed MZGC strategy for fingerprint imaging and recognition with their resistance to stray light interference. By applying the mixture of MZGC and MZG, we realized ratiometric temperature sensing at 35–40 °C within body temperature range. The optical mechanism clearly illustrated for tri-modality applications as bioimaging, fingerprint recognition, and temperature sensing. This work provides a reliable method for the improvement of optical properties and thus extend the applications of persistent luminescence nanoparticles.

X-ray activated near-infrared persistent luminescence nanoparticles for trimodality in vivo imaging.

As promising luminescence nanoparticles, near-infrared (NIR) persistent luminescence nanoparticles (PLNPs) have received extensive attention in the field of high-sensitivity bioimaging in recent years. However, NIR PLNPs face problems such as short excitation wavelengths and single imaging modes, which limit their applications in in vivo reactivated imaging and multimodal imaging. Here, we report for the first time novel Gd2GaTaO7:Cr3+,Yb3+ (GGTO) NIR PLNPs that integrate X-ray activated NIR persistent luminescence (PersL), high X-ray attenuation and excellent magnetic properties into a single nanoparticle (NP). In this case, Cr3+ is used as the luminescence center. The co-doped Yb3+ and coating effectively enhance the X-ray activated NIR PersL. At the same time, the presence of the high-Z element Ta also makes the GGTO NPs exhibit high X-ray attenuation performance, which can be used as a CT contrast agent to achieve in vivo CT imaging. In addition, since the matrix contains a large amount of Gd, the GGTO NPs show remarkable magnetic properties, which can realize in vivo MR imaging. GGTO NPs combine the trimodal benefits of X-ray reactivated PersL, CT and MR imaging and are suitable for single or combined applications that require high sensitivity and spatial resolution imaging.

Persistent luminescent metal-organic framework nanocomposite enables autofluorescence-free dual modal imaging-guided drug delivery.

Molecular imaging-guided therapy was essential for realizing precise cancer intervention, while designing an imaging platform to achieve autofluorescence-free imaging for dual modal imaging-guided drug delivery remains a challenge. Near-infrared persistent luminescence nanoparticles (NIR PLNPs) were promising for tumor imaging due to no background interference from the tissue. Herein, a persistent luminescent metal-organic framework (PLNPs@MIL-100(Fe)) is prepared via a layer-by-layer method for dual-modal imaging-guided drug delivery. The PLNPs@MIL-100(Fe) exhibit NIR persistent luminescence emitting and T2-weighted signal, achieving precise in vivo dual-modal imaging of tumor-bearing mice by providing high spatial resolution MR imaging and autofluorescence-free NIR imaging. The porous MIL-100(Fe) shell provides PLNPs@MIL-100(Fe) with up to 87.1% drug loading capacity and acid-triggered drug release for drug delivery. We envision that the proposed PLNPs@MIL-100(Fe) platform would provide an effective approach for precise tumor imaging and versatile drug delivery.

Dual-Triggered Near-Infrared Persistent Luminescence Nanoprobe for Autofluorescence-Free Imaging-Guided Precise Therapy of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a common, chronic, and highly disabling autoimmune disease characterized by difficult treatment, long disease duration, and easy recurrence. The development and application of high-sensitivity theranostic probes for RA that will facilitate precise monitoring of disease progression and enable effective treatment are currently hotspots in the field of RA theranostics. In this study, mZMI@HA, a dual-triggered theranostics nanoprobe, is constructed based on near-infrared persistent luminescence nanoparticles (NIR-PLNPs) for precise RA treatment and therapeutic evaluation. This is the first reported use of high-sensitivity autofluorescence-free imaging based on NIR-PLNPs for precise RA treatment and therapeutic evaluation. Compared with the NIR fluorescence imaging probe-indocyanine green, the signal-to-background ratio of persistent luminescence (PersL) imaging is improved nearly 14-fold. Using PersL imaging to guide photothermal therapy and controllable drug release through NIR/pH-responsiveness, the progress of collagen-induced RA is relieved. Additionally, the therapeutic evaluation of RA by PersL imaging is consistent with clinical micro-computed tomography and histological analyses. This study demonstrates the potential of NIR-PLNPs for high-sensitivity imaging-guided RA treatment, providing a new strategy for RA precise theranostics.

LiGa5O8:Cr3+@PEG nanomaterials with near-infrared-persistent luminescence for bioimaging applications

Bioimaging is considered a convincing imaging method. The near-infrared Persistent Luminescence Nanoparticles(NIR PLNPS) have demonstrated great perspectives for application in the bioimaging field due to their unique optical properties. The high-temperature solid-phase(HT) methods cannot be used for bioimaging applications due to the existence of large particle size. On the other hand, the sol-gel (S-G) and the hydrothermal(Hy) methods can successfully prepare the LGO: Cr nanomaterials. In this work, a LiGa5O8:Cr3+(LGO: Cr) NIR PLNPS was prepared by S-G and Hy methods, and the employed nanomaterials were treated by PEG(Polyethylene glycol) modification to reduce the toxicity. The acquired results clearly show that the average particle size of the samples that were prepared by enforcing the S-G method is larger than that of the Hy method. However, their luminescence performance is better than that of the samples prepared by Hy method, and there are differences in trap characteristics. Synthetically, LGO: Cr@PEG(Hy) is suited for biological imaging due to its lower toxicity, and cell imaging by LGO: Cr@PEG(Hy)was successfully achieved.

Autofluorescence free detection of carcinoembryonic antigen in pleural effusion by persistent luminescence nanoparticle-based aptasensors

Carcinoembryonic antigen (CEA) is an important biomarker in the diagnosis of cancer. The increase of CEA in malignant pleural effusion appears earlier and possesses higher clinical diagnostic value than that in the serum. Conventional fluorescent probes suffer from the interference of strong biotissue auto-fluorescence, which limits severely their applications in biology detection. Herein, a novel fluorescence aptasensor was designed with near-infrared persistent luminescence nanoparticles (PLNPs) for accurate detection of carcinoembryonic antigen in pleural effusion by FRET quenching and recovery mechanism. The strong background interference from the autofluorescence of pleural effusion samples can be effectively eliminated and extra increments of measured values originated from the background of different samples were ruled out, benefit from the long decay time of PLNPs and time-resolved fluorescence technology. The detection results show high accuracy of the measured values of carcinoembryonic antigen both in cancer and benign disease group with low detection limit up to 0.0851 pg mL−1. Furthermore, excellent selectivity from coexisting biomarker was achieved by the hybridization between the aptamer and the complementary DNA on PLNPs surface. Hence, the established near-infrared PLNPs-based aptasensors offer excellent performance with high selective, accuracy and signal-to-noise ratio for detection of carcinoembryonic antigen in pleural effusion.

Low-dose X-ray-stimulated LaGaO3:Sb,Cr near-infrared persistent luminescence nanoparticles for deep-tissue and renewable in vivo bioimaging

X-ray-stimulated near-infrared persistent luminescence nanoparticles (NIR-PLNPs) offer attractive capabilities for autofluorescence free deep-seated imaging and depth-independent treatment, but still suffer from adverse effects caused by high-dose X-ray irradiation (>5 Gy). From the viewpoint of two centers of NIR-PLNPs, i.e., X-ray photon absorption center and defects center, we here propose a top-down composition design strategy for the development of low dose X-ray-stimulated NIR-PLNPs with improved X-ray photon absorption efficiency and optimized persistent luminescence (PersL) performance. Successfully, hypersensitive X-ray-stimulated NIR-PLNPs LaGaO3:Sb3+,Cr3+ with a super-long PersL emission (>500 h) at ∼750 nm are prepared. The nature of high Z atomic constituents of the host LaGaO3 endows these NIR-PLNPs with strong X-ray absorption capacity. Simply by codoping with size-mismatched ions Sb3+, the concentration of oxygen vacancies in the host is rationally optimized, leading to the enhanced NIR PersL performance of Cr3+ ions. In vivo bioimaging demonstrates that the designed X-ray-stimulated NIR-PLNPs LaGaO3:Sb3+,Cr3+ can be readily reactivated under X-ray irradiation with even a lower dose to 0.37 Gy, showing the advantages of these nanoparticles on deep-seated imaging and treatment. More importantly, we anticipate that our proposed top-down composition design strategy can be applied to develop much low dose X-ray-stimulated NIR-PLNPs in the future.

Tin-Doped Near-Infrared Persistent Luminescence Nanoparticles with Considerable Improvement of Biological Window Activation for Deep Tumor Photodynamic Therapy.

The photodynamic therapy (PDT) as a promising antitumor therapy technique is greatly hampered by the low tissue penetration of light and the photothermal effect of prolonged irradiation. Near-infrared (NIR) persistent luminescence nanoparticles (NPLNPs) possess the potential for application in next-generation PDT. However, owing to the low re-excitation efficiency of NPLNPs in deep tissue, the current PDT nanoplatform based on NPLNPs is faced with the disadvantage of decreased PDT efficiency induced by persistent luminescence (PersL) decay at the lesion site. Herein, NPLNPs, Zn1.3Ga1.4Sn0.3O4:Cr3+ (ZGS), with small particle sizes and excellent optical properties are synthesized via a simple acetylacetonate combustion method. The ZGS can be repeatedly excited by the biological window (659 nm) light to produce a strong NIR (700 nm) PersL. The response efficiency of ZGS to the wavelength in the biological window has been greatly improved by doping Sn4+ into the ZnGa2O4 matrix, which is 55 times higher than that of traditional ZnGa2O4:Cr3+. We further develop a PDT nanoplatform by modifying a photosensitizer on its surface. The PDT experiments show that the developed nanoplatform can achieve continuous and efficient tumor PDT with a depth of up to 3 cm by repeated excitation using a 659 nm LED. The NPLNPs largely solve the problem of the low re-excitation efficiency after NIR PersL decay of traditional NPLNPs in deep tissue applications and will further promote the application of NIR PLNPs in the biomedical field.

Visualization of inflammation in a mouse model based on near-infrared persistent luminescence nanoparticles

Inflammation is implicated in many human diseases, thus the diagnosis of inflammation is very important for the early treatment of diseases associated with inflammation. However, the high-sensitivity diagnosis of inflammation remains difficult. Near-infrared (NIR) persistent luminescence nanoparticles (PLNPs) were considered one of the most promising candidates for high-sensitivity bioimaging due to being free of autofluorescence. In this study, we synthesized PLNPs Zn1.1Ga1.8Ge0.1O4:Cr3+ (ZGG) which demonstrated low cytotoxicity, excellent NIR persistent luminescence. We conducted the visualization of inflammation using these nanoparticles. The results indicated that the surface states of the ZGG influenced the progression of macrophage phagocytosis in vitro. ZGG-NH2 demonstrated higher levels of internalization compared with ZGG-OH and ZGG-PEG. However, in contrast to the in vitro results, ZGG-PEG exhibited a greater ability to facilitate the visualization of inflammation in vivo. The long chains of PEG on the ZGG-PEG surfaces resulted in a lower reticuloendothelial system capture rate compared with both ZGG-OH and ZGG-NH2. A higher concentration of the ZGG-PEG would cycle through the inflammation site, thereby inducing a high level of ZGG-PEG retention and thus yielding the strongest luminescent signal. Taken together, the results of this study demonstrate a simple and novel method for high-sensitivity visualization of inflammation in vivo.

Long-term in vivo biodistribution and toxicity study of functionalized near-infrared persistent luminescence nanoparticles

Near-infrared (NIR) persistent luminescence nanoparticles (NPLNPs) have become one of the most promising candidates for bioimaging. Different from the other fluorescence nanoprobes, the NIR persistent luminescence of NPLNPs can last for a long time after excitation, double exposure that is nanoparticles and light exist during the long-term bioimaging. However, to date, the potential risk of nanoparticles and NIR persistent luminescence of NPLNPs is still unknown. In this study, Cr3 + -doped zinc gallate, Zn1.1Ga1.8Sn0.1O4:Cr3+ (ZGO), the most promising NPLNPs in bioimaging, was chosen as a representative for potential risk assessment. We evaluated the potential risk of nanoparticles and NIR persistent luminescence of ZGO for a long period of time. In vitro study showed that the ZGO possessed a low cytotoxicity. In vivo biodistribution results showed that the ZGO mainly accumulated in the reticuloendothelial system after intravenous injection and could be gradually cleared from the body by digestive system. In addition, the ZGO did not exhibit appreciable toxicity in mice over a period of 60 days. It’s also worth mentioning that long-term NIR persistent luminescence of ZGO did not exhibit obvious toxicities both in vitro and in vivo. Our results provide important information with regards to the risk of NPLNPs in long-term bioimaging.

A new near-infrared persistent luminescence nanoparticle as a multifunctional nanoplatform for multimodal imaging and cancer therapy

Multifunctional nanoplatforms with multimodal imaging and cancer therapy capabilities have attracted attention in biomedical applications. Near-infrared persistent luminescence nanoparticles (NPLNPs) were considered one of the most promising candidates for constructing multifunctional nanoplatforms due to the absence of in situ excitation and high signal-to-noise ratios (SNRs). Here, we report a novel NPLNP mSiO2@Gd3Ga5O12:Cr3+, Nd3+ (mSiO2@GGO) as multifunctional nanoplatforms for multimodal imaging and cancer therapy. These NPs exhibited a persistent luminescence (745 nm) of more than 3 h in the first near-infrared window (NIR-I) after UV excitation, which can realize high SNRs and long-term in vivo imaging. Moreover, these NPs showed excellent NIR luminescence (1067 nm) in the second near-infrared window (NIR-II) under 808 nm excitation, which is more suitable for deep tissue imaging due to the lower photon scattering and deeper tissue penetration of NIR-II luminescence. Furthermore, the host Gd3Ga5O12 with high Gd3+ concentration showed a high r1 value (10.70 mM−1 s−1) and was suitable for T1 MR imaging. The mesoporous silica nanoparticles (mSiO2) served as a framework to control the mSiO2@GGO particle morphology and provide low toxicity and drug loading capacity for cancer therapy.

Liposome-Coated Persistent Luminescence Nanoparticles as Luminescence Trackable Drug Carrier for Chemotherapy.

Near-infrared persistent luminescence nanoparticles (NIR-PLNPs) are promising imaging agents due to deep tissue penetration, high signal-to-noise ratio, and repeatedly charging ability. Here, we report liposome-coated NIR-PLNPs (Lipo-PLNPs) as a novel persistent luminescence imaging guided drug carrier for chemotherapy. The Lipo-PLNP nanocomposite shows the advantages of superior persistent luminescence and high drug loading efficiency and enables autofluorescence-free and long-term tracking of drug delivery carriers with remarkable therapeutic effect.

Synthesis of functionalized triple-doped zinc gallogermanate nanoparticles with superlong near-infrared persistent luminescence for long-term orally administrated bioimaging.

Near-infrared persistent luminescence nanoparticles (NIR-PLNPs) have great potential for bioimaging because of no need for in situ excitation, negligible autofluorescence background and deep tissue penetration in optical detection. However, it is challenging to synthesize monodispersed nanosize NIR-PLNPs along with high quantum yield and long afterglow. Here, we show a surfactant-aided hydrothermal method in combination with a short time calcination and a post hydrothermal procedure for the synthesis of ultra-bright monodispersed triple-doped zinc gallogermanate nanostructures with super-long near-infrared persistent luminescence (ZGGO:Cr(3+),Yb(3+),Er(3+)). The ZGGO:Cr(3+),Yb(3+),Er(3+) exhibits NIR emission with high quantum yield (9.86%), superlong afterglow time (>20 days), monodispersed nanosize, red light renewability, excellent biocompatibility, and low toxicity. The effective red LED light activation of the persistent luminescence of ZGGO:Cr(3+),Yb(3+),Er(3+) with no need for UV pre-irradiation permits the material for long-term in vivo bioimaging application. We also show for the first time the better targeting performance of the oral administration of folate acid functionalized ZGGO:Cr(3+),Yb(3+),Er(3+) for tumor-targeting bioimaging than conventional intravenous injection. We believe that the ZGGO:Cr(3+),Yb(3+),Er(3+) will open new perspectives for orally administrated optical imaging and for diagnosis applications.

The in vivo activation of persistent nanophosphors for optical imaging of vascularization, tumours and grafted cells

Optical imaging for biological applications requires more sensitive tools. Near-infrared persistent luminescence nanoparticles enable highly sensitive in vivo optical detection and complete avoidance of tissue autofluorescence. However, the actual generation of persistent luminescence nanoparticles necessitates ex vivo activation before systemic administration, which prevents long-term imaging in living animals. Here, we introduce a new generation of optical nanoprobes, based on chromium-doped zinc gallate, whose persistent luminescence can be activated in vivo through living tissues using highly penetrating low-energy red photons. Surface functionalization of this photonic probe can be adjusted to favour multiple biomedical applications such as tumour targeting. Notably, we show that cells can endocytose these nanoparticles in vitro and that, after intravenous injection, we can track labelled cells in vivo and follow their biodistribution by a simple whole animal optical detection, opening new perspectives for cell therapy research and for a variety of diagnosis applications.