Synthesis of Persistent Luminescent Nanoparticles for Rewritable Displays and Illumination Applications

Persistent luminescent nanoparticles (PLNPs) possess the capabilities to maintain extended longevity and robust emission even after the excitation has ...

Shanghai Tech University

Photothermal therapy (PTT) is a potentially advanced strategy for highly precise cancer treatment. Tumor-microenvironment-activatable agents provide useful tools for PTT, but their photothermal conversion capacities vary and cannot be evaluated in vivo; thus, a general PTT prescription does not work with individual activatable agents. Here, glutathione (GSH)-activatable nanocomposites, silicomolybdate-functionalized NaLuF :Yb,Er@NaLuF @NaLuF :Nd are prepared, for customized PTT of subcutaneous orthotopic cancer. By simultaneously determining intratumoral GSH concentration and the amount of accumulated agent using multiple orthogonal luminescent emissions of nanocomposites, near-infrared absorbance of photothermal conversion agents is evaluated in vivo, based on the optimized irradiating prescriptions (irradiating power density and time) established. This allows customized PTT of each individual case with high efficacy and viability. This work also includes a method for investigating individual intratumoral variation, and the development of the next generation of customized nanomedicine for efficacious PTT of subcutaneous orthotopic cancer.

Customized Photothermal Therapy of Subcutaneous Orthotopic Cancer by Multichannel Luminescent Nanocomposites.

Wavelength-dependent absorbance of blood has impeded the development of fluorescence biodetection in whole blood. Here, by replacing the fluorescence working signal with a temperature signal, reliable HS detection was performed in samples of whole blood. The developed system was based on a dual-channel lanthanide-doped nanoprobe, which further allowed precise serodiagnosis of acute pancreatitis.

Dual-channel lanthanide-doped nanoprobe for reliable multi-signal ratiometric detection of HS in whole blood.

Lanthanide luminescence nanothermometers (LNTs) provide microscopic, highly sensitive, and visualizable optical signals for reporting temperature information, which is particularly useful in biomedicine to achieve precise diagnosis and therapy. However, LNTs with efficient emissions at the long-wavelength region of the second and the third near-infrared (NIR-II/III) biological window, which is more favourable for  thermometry, are still limited. Herein, we present a lanthanide-doped nanocomposite with Tm and Nd ions as emitters working beyond 1200 nm to construct a dual ratiometric LNT. The cross-relaxation processes among lanthanide ions are employed to establish a strategy to enhance the NIR emissions of Tm for bioimaging-based temperature detection . The dual ratiometric probes included in the nanocomposite have potential in monitoring the temperature difference and heat transfer at the nanoscale, which would be useful in modulating the heating operation more precisely during thermal therapy and other biomedical applications. This work not only provides a powerful tool for temperature sensing  but also proposes a method to build high-efficiency NIR-II/III lanthanide luminescent nanomaterials for broader bio-applications.

A lanthanide nanocomposite with cross-relaxation enhanced near-infrared emissions as a ratiometric nanothermometer.

Simultaneous photothermal ablation of multiple tumors is limited by unpredictable photo-induced apoptosis, caused by individual intratumoral differences. Here, a multi-channel lanthanide nanocomposite was used to achieve tailored synergistic treatment of multiple subcutaneous orthotopic tumors under non-uniform whole-body infrared irradiation prescription. The nanocomposite reduces intratumoral glutathione by simultaneously activating the fluorescence and photothermal channels. The fluorescence provides individual information on different tumors, allowing customized prescriptions to be made. This enables optimal induction of hyperthermia and dosage of chemo drugs, to ensure treatment efficacy, while avoiding overtherapy. With an accessional therapeutic laser system, customized synergistic treatment of subcutaneous orthotopic cancer cases with multiple tumors is possible with both high efficacy and minimized side effects.

Multi-Channel Lanthanide Nanocomposites for Customized Synergistic Treatment of Orthotopic Multi-Tumor Cases.

Tumor vascular disruption has become a promising strategy for cancer therapy in recent decades. Nanocomposites loaded with therapeutic materials and drugs are expected to improve the accuracy of anti-vascular therapy and minimize side effects. However, how to prolong blood circulation of therapeutic nanocomposites for enhanced accumulation in tumor vasculature and how to monitor the initial efficacy of anti-vascular therapy for early evaluation of prognosis remain unsolved. Herein, a biomimetic nanosystem consisting of erythrocyte membrane modified nanocomposites (CMNCs) is developed for cooperation to achieve anti-vascular cancer therapy and initial efficacy monitoring. By utilizing poly(lactic--glycolic acid) (PLGA) as the interface material, functional nanomaterials and drug molecules are successfully integrated into CMNCs. The long circulation and immune escape features of the erythrocyte membrane facilitate CMNCs loaded with photothermal agents and chemodrugs to be delivered to the tumor region for anti-vascular treatment. Furthermore, the vascular damage-induced haemorrhage and the following coagulation process is labelled by near infrared emissive CMNCs to indicate the initial therapeutic efficacy of the treatment. This work not only points to a biomimetic strategy for conquering the challenges in anti-vascular cancer therapy, but also provides insights into the biological responses of erythrocyte membrane modified nanocomposites to exploit their biomedical applications.

An erythrocyte membrane-modified biomimetic synergistic nanosystem for cancer anti-vascular therapy and initial efficacy monitoring.

Recyclable fluorescence assays that can be stored at room temperature would greatly benefit biomedical diagnostics by bringing sustainability and cost-efficiency, especially for point-of-care serodiagnostics in developing regions. Here, a general strategy is proposed to generate recyclable fluorescent probes by using engineered enzymes with enhanced thermo-/chemo-stability, which maintains an outstanding serodiagnostic performance (accuracy >95%) after 10 times of recycling as well as after storage at elevated temperatures (37 °C for 10 days). With these three outstanding properties, recyclable fluorescent probes can be designed to detect various biomarkers of clinical importance by using different enzymes.

Recyclable and Robust Optical Nanoprobes with Engineered Enzymes for Sustainable Serodiagnostics.

Osteoporosis (OP), which largely increases the risk of fractures, is the most common chronic degenerative orthopedic disease in the elderly due to the imbalance of bone homeostasis. Alpha-ketoglutaric acid (AKG), an endogenous metabolic intermediate involved in osteogenesis, plays critical roles in osteogenic differentiation and mineralization and the inhibition of osteoclastogenic differentiation. However, the low bioavailability and poor bone-targeting efficiency of AKG seriously limit its efficacy in OP treatment. In this work, a bone-targeting, near-infrared emissive lanthanide luminescence nanocarrier loaded with AKG (β-NaYF:7%Yb, 60%Nd@NaLuF@mSiO-EDTA-AKG, abbreviated as LMEK) is developed for the enhancement of AKG efficacy in OP therapy. By utilizing the NIR-II luminescence (>1000 nm) of LMEK, whole-body bone imaging with high spatial resolution is achieved to confirm the bone enrichment of AKG noninvasively in vivo. The results reveal that LMEK exhibits a remarkable OP therapeutic effect in improving the osseointegration of the surrounding bone in the ovariectomized OP mice models, which is validated by the enhanced inhibition of osteoclast through hypoxia-inducible factor-1α suppression and promotion of osteogenic differentiation in osteoblast. Notably, the dose of AKG in LMEK can be reduced to only 0.2 % of the dose when pure AKG is used in therapy, which dramatically improves the bioavailability of AKG and mitigates the metabolism burden. This work provides a strategy to conquer the low utilization of AKG in OP therapy, which not only overcomes the challenges in AKG efficacy for OP treatment but also offers insights into the development and application of other potential drugs for skeletal diseases. STATEMENT OF SIGNIFICANCE: Alpha-ketoglutarate (AKG) is an intermediate within the Krebs cycle, participating in diverse metabolic and cellular processes, showing potential for osteoporosis (OP) therapy. However, AKG's limited bioavailability and inefficient bone-targeting hinder its effectiveness in treating OP. Herein, a near-infrared emissive nanocarrier is developed that precisely targets bones and delivers AKG, bolstering its effectiveness in OP therapy. Thanks to this efficient bone-targeting delivery, the AKG dosage is reduced to 0.2 % of the conventional treatment level. This marks the first utilization of a bone-targeting nanocarrier to amplify AKG's bioavailability and OP therapy efficacy. Furthermore, the mechanism of AKG-loaded nanocarrier regulating the biological behavior of osteoclasts and osteoblasts mediated is tentatively explored.

A bone-targeting near-infrared luminescence nanocarrier facilitates alpha-ketoglutarate efficacy enhancement for osteoporosis therapy.

 transmembrane-voltage detection reflected the electrophysiological activities of the biological system, which is crucial for the diagnosis of neuronal disease. Traditional implanted electrodes can only monitor limited regions and induce relatively large tissue damage. Despite emerging monitoring methods based on optical imaging have access to signal recording in a larger area, the recording wavelength of less than 1000 nm seriously weakens the detection depth and resolution . Herein, a Förster resonance energy transfer (FRET)-based nano-indicator, NaYbF:Er@NaYF@Cy7.5@DPPC (Cy7.5-ErNP) with emission in the near-infrared IIb biological window (NIR-IIb, 1500-1700 nm) is developed for transmembrane-voltage detection. Cy7.5 dye is found to be voltage-sensitive and is employed as the energy donor for the energy transfer to the lanthanide nanoparticle, NaYbF:Er@NaYF (ErNP), which works as the acceptor to achieve electrophysiological signal responsive NIR-IIb luminescence. Benefiting from the high penetration and low scattering of NIR-IIb luminescence, the Cy7.5-ErNP enables both the visualization of action potential  and monitoring of Mesial Temporal lobe epilepsy (mTLE) disease . This work presents a concept for leveraging the lanthanide luminescent nanoprobes to visualize electrophysiological activity , which facilitates the development of an optical nano-indicator for the diagnosis of neurological disorders.

An NIR-IIb emissive transmembrane voltage nano-indicator for the optical monitoring of electrophysiological activities .

Nanothermometers enable the detection of temperature changes at the microscopic scale, which is crucial for elucidating biological mechanisms and guiding treatment strategies. However, temperature monitoring of micron-scale structures in vivo using luminescent nanothermometers remains challenging, primarily due to the severe scattering effect of biological tissue that compromises the imaging resolution. Herein, a lanthanide luminescence nanothermometer with a working wavelength beyond 1500 nm is developed to achieve high-resolution temperature imaging in vivo. The energy transfer between lanthanide ions (Er and Yb) and HO molecules, called the environment quenching assisted downshifting process, is utilized to establish temperature-sensitive emissions at 1550 and 980 nm. Using an optimized thin active shell doped with Yb ions, the nanothermometer's thermal sensitivity and the 1550 nm emission intensity are enhanced by modulating the environment quenching assisted downshifting process. Consequently, minimally invasive temperature imaging of the cerebrovascular system in mice with an imaging resolution of nearly 200 μm is achieved using the nanothermometer. This work points to a method for high-resolution temperature imaging of micron-level structures in vivo, potentially giving insights into research in temperature sensing, disease diagnosis, and treatment development.

Lanthanide luminescence nanothermometer with working wavelength beyond 1500 nm for cerebrovascular temperature imaging in vivo.

The photothermal therapeutic effect on tumors located at different subcutaneous depths varies due to the attenuation of light by tissue. Here, based on the wavelength-dependent optical attenuation properties of tissues, the tumor depth is assessed using a multichannel lanthanide nanocomposite. A zeolitic imidazolate framework (ZIF-8)-coated nanocomposite is able to deliver high amounts of the hydrophilic heat shock protein 90 inhibitor epigallocatechin gallate through a hydrogen-bonding network formed by the encapsulated highly polarized polyoxometalate guest. It is superior to both bare and PEGylated ZIF-8 for drug delivery. With the assessment of tumor depth and accumulated amount of nanocomposite by fluorescence, an irradiation prescription can be customized to release sufficient HSP90 inhibitor and generate heat for sensitized photothermal treatment of tumors, which not only ensured therapeutic efficacy but also minimized damage to the surrounding tissues.

Customized Enhancement of Thermal Sensitivity of Tumors at Different Subcutaneous Depths by Multichannel Lanthanide Nanocomposites.

Room temperature phosphorescence (RTP) materials with wood as framework are highly desirable due to their extended afterglow, high haze and good mechanical properties, which is highly desired in lighting materials. However, it remains challenging to obtain wood-based RTP materials that possess on-demand afterglow colors while maintaining high transparency across the entire visible spectrum. In this study, long-persistent phosphorescent transparent composite with tunable afterglow color is fabricated by infiltrating delignified wood with phosphors (including carbazole, naphthalene, and pyrene) doped polymethyl methacrylate (PMMA). Such RTP woods indicate remarkable transparency, over 70 %, and an extended afterglow duration of up to 8 s. Here, PMMA serves as rigid surrounding to suppress the non-radiative transition of phosphors to ensure phosphorescence, and to fulfill in the wood lumen to match the refractive index of cellulose for transparency. By formulating phosphors with different types and concentration ratios, transparent woods with diverse phosphorescence colors, and white emission, are successfully achieved. Furthermore, the RTP woods demonstrate dynamically tunable afterglow colors over time based on the varied phosphorescent lifetimes. Characterized by their high transparency and tunable colors, these natural wood-based RTP materials have great potentials for application in the fields of LED materials, optics, and building materials.

Xingjun Zhu

School of Physical Science and Technology

Shanghai Tech University

Synthesis of Persistent Luminescent Nanoparticles for Rewritable Displays and Illumination Applications

Xingjun Zhu

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}School of Physical Science and Technology

Shanghai Tech University

Synthesis of Persistent Luminescent Nanoparticles for Rewritable Displays and Illumination Applications

School of Physical Science and Technology