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Nanothermometers can detect changes in the local temperature in living cells and in vivo, revealing fundamental biological properties. Despite the exploration of different temperature-responsive materials, the design and development of temperature-sensing probes with high brightness and high sensitivity remain a daunting challenge. Here, we employed the UiO-66 type metal-organic frameworks (MOFs) to anchor UNCPs on the surface of the MOFs for constructing MOF@UCNPs nanohybrids. The in situ composite method with MOFs leads to the coordination interaction between the ligands and the surface of UCNPs, enabling controlled composite formation between different MOFs and UCNPs. Remarkably, the surface interaction favors the anomalous thermo-enhanced luminescence, achieving a 35-fold enhancement of UiO-66@NaYF 4 :Yb/Tm at 413 K. Furthermore, these MOF@UCNPs nanohybrids with thermo-enhanced luminescence are developed as multifunctional biological probes for bioimaging and intracellular temperature sensing, demonstrating a high thermal sensitivity of 1.92% K -1 in the physiological temperature range. Based on these findings, temperature monitoring of the local position was successfully carried out by the designed MOF@UCNPs nanoprobes in vivo. These findings underscore the potential of MOF@UCNPs nanohybrids, opening up new avenues for the development of a multifunctional platform for biological analysis.

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-PEG 2000 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.

Multicolor tunable upconversion nanoparticles (UCNPs) have garnered attention owing to their diverse applications such as displays, imaging, and security. Typically, achieving multicolor emission from UCNPs requires complicated core/multishell nanostructures comprising a core with at least five shells. Here, we propose a strategy to achieve bright and orthogonal red (R), green (G), and blue (B) upconversion (UC) luminescence without synthesizing complicated core/quintuple-shell or core/sextuple-shell nanostructures. For achieving bright and orthogonal RGB triprimary color UC luminescence, orthogonal bicolor-emitting core/shell-structured UCNPs are synthesized and blended. Orthogonal RB, RG, and GB luminescence are achieved through photon blocking. The combination of two orthogonal bicolor-emitting UCNPs exhibits pure RGB UC luminescence and full-color tunability via manipulation of excitation laser conditions. Furthermore, we present color displays achieved with transparent UCNP-polymer composites utilizing three distinct near-infrared light wavelengths, implying that the proposed strategy for attaining RGB UC luminescence may facilitate advancements in the development of full-color volumetric displays.

Upconversion nanoparticles (UCNPs) are materials that provide unique advantages for biomedical applications. There are constantly emerging customized UCNPs with varying compositions, coatings, and upconversion mechanisms. Cellular uptake is a key parameter for the biological application of UCNPs. Uptake experiments have yielded highly varying results, and correlating trends between cellular uptake with different types of UCNP coatings remains challenging. In this report, the impact of surface polymer coatings on the formation of protein coronas and subsequent cellular uptake of UCNPs by macrophages and cancer cells was investigated. Luminescence confocal microscopy and elemental analysis techniques were used to evaluate the different coatings for internalization within cells. Pathway inhibitors were used to unravel the specific internalization mechanisms of polymer-coated UCNPs. Coatings were chosen as the most promising for colloidal stability, conjugation chemistry, and biomedical applications. PIMA-PEG (poly(isobutylene- alt -maleic) anhydride with polyethylene glycol)-coated UCNPs were found to have low cytotoxicity, low uptake by macrophages (when compared with PEI, poly(ethylenimine)), and sufficient uptake by tumor cells for surface-loaded drug delivery applications. Inductively coupled plasma-optical emission spectroscopy (ICP-OES) studies revealed that PIMA-coated NPs were preferentially internalized by the clathrin- and caveolar-independent pathways, with a preference for clathrin-mediated uptake at longer time points. PMAO-PEG (poly(maleic anhydride- alt -1-octadecene) with polyethylene glycol)-coated UCNPs were internalized by energy-dependent pathways, while PAA- (poly(acrylic acid)) and PEI-coated NPs were internalized by multifactorial mechanisms of internalization. The results indicate that copolymers of PIMA-PEG coatings on UCNPs were well suited for the next-generation of biomedical applications.

Herein, a flexible near-infrared (NIR) light-actuated photoelectrochemical (PEC) lab-on-paper device was constructed toward miRNA-122 detection, utilizing the combination of DNA-programmed NaYF 4 /Yb,Tm upconversion nanoparticles (UCNPs) and the Z -scheme AgI/WO 3 heterojunction grown in situ on gold nanoparticle-decorated 3D cellulose fibers. The UCNPs were employed as light transducers for converting NIR light into ultraviolet/visible (UV/vis) light to excite the nanojunction. The multiple diffraction of NaYF 4 /Yb,Tm matched the absorption band of the Z -scheme AgI/WO 3 heterojunction, resulting in enhanced PEC photocurrent output. This prepared Z -scheme heterojunction effectively directed charge migration and highly facilitated the electron-hole pair separation. Target miRNA-122 activated the nonenzyme catalytic hairpin assembly signal amplification strategy, generating duplexes which caused the exfoliation of NaYF 4 /Yb,Tm UCNPs from the biosensor electrode and lowered the photocurrent under 980 nm irradiation. Under optimized circumstances, the proposed NIR-actuated PEC lab-on-paper device presented accurate miRNA-122 detection within a wide linear range of 10 fM-100 nM with a low limit of detection of 2.32 fM, providing a reliable strategy in the exploration of NIR-actuated PEC biosensors for low-cost, high-performance bioassay in clinical applications.

Rapid maxillary expansion (RME) is a common therapy for maxillary transverse deficiency. However, relapses after RME usually occur because of insufficient bone formation. MicroRNA-21 (miR-21) was reported as an important post-transcriptional modulator for osteogenesis. Herein, a photocontrolled miR-21 (PC-miR-21)-loaded nanosystem using upconversion nanoparticles (UCNPs) modified with poly(ether imide) (PEI), i.e., UCNPs@PEI@PC-miR-21, was constructed to promote bone formation in the midpalatal suture. UCNPs@PEI was constructed as the light transducer and delivery carrier. The UCNPs@PEI@PC-miR-21 nanocomplexes have good aqueous dispersibility and biocompatibility. The in vitro cell experiment suggested that UCNPs@PEI could protect PC-miR-21 from biodegradation and release PC-miR-21 into the cytoplasm under near-infrared light (NIR) irradiation. Furthermore, UCNPs@PEI@PC-miR-21 upregulated the expression of the osteogenic key markers, ALP, RUNX2, and COL1A1, at the levels of both genes and proteins. Besides, the results of the in vivo RME mice models further corroborated that photocontrollable UCNPs@PEI@PC-miR-21 accelerated bone formation with upregulating osteogenic markers of ALP, RUNX2, and osteoprotegerin and inducing fewer osteoclasts formation. In conclusion, UCNPs@PEI@PC-miR-21 nanoparticles with a NIR light could facilitate the remote and precise delivery of exogenous miR-21 to the midpalatal suture to promote bone formation during RME. This work represents a cutting-edge approach of gene therapy to promote osteogenesis in the midpalatal suture during RME and provides a frontier scientific basis for later clinical treatment.

The effect of photodynamic therapy (PDT) is severely limited by tumor hypoxia and the short half-life of reactive oxygen species (ROS). Herein, we constructed a near-infrared (NIR) light-regulated PDT nanoplatform (TPP-UCNPs@MOF-Pt) consisting of an upconversion nanoparticle (UCNP) core and porphyrin-based metal-organic framework (MOF) shell with platinum nanoparticles (PtNPs) and a mitochondria-targeting triphenylphosphine (TPP) group on the surface. TPP-UCNPs@MOF-Pt could effectively relieve the tumor hypoxia by converting intracellular H 2 O 2 to oxygen (O 2 ) and elevated the ROS level to enhance PDT efficacy under NIR light irradiation. In addition, the mitochondria-targeting TPP-UCNPs@MOF-Pt was localized on the mitochondria, leading to severe depolarization of the mitochondrial membrane and activation of the apoptotic pathway, further amplifying the therapeutic efficacy. In vitro and in vivo experiments demonstrated that the greatly enhanced photodynamic therapeutic efficacy of TPP-UCNPs@MOF-Pt was achieved by combining relief of tumor hypoxia with mitochondrial targeting and NIR activation. This study provides a promising strategy for construction of an MOF-based multifunctional nanoplatform to address the current limitations of PDT treatment for hypoxic tumors.

This study prepared dumbbell-shaped titanium dioxide (TiO 2 )/gold nanorods (AuNRs) coated with mesoporous silica shells (mS) (AuNRs-TiO 2 @mS). Methotrexate (MTX) was further loaded into the AuNRs-TiO 2 @mS, and then upconversion nanoparticles (UCNPs) were decorated to form AuNRs-TiO 2 @mS-MTX: UCNP nanocomposites. TiO 2 is used as an intense photosensitizer (PS) to produce cytotoxic reactive oxygen species (ROS), leading to photodynamic therapy (PDT). Concurrently, AuNRs exhibited intense photothermal therapy (PTT) effects and photothermal conversion efficiency. In vitro results suggested that these nanocomposites can kill oral cancer cells (HSC-3) without toxicity through irradiation of NIR laser, owing to the synergistic effect. The in vivo studies indicated that these nanocomposites exhibited excellent antitumor effects through synergistic PDT/PTT/chemotherapy under a near-infrared (NIR) 808 nm laser irradiation. Thus, these AuNRs-TiO 2 @mS: UCNP nanocomposites have great potential to undergo deep tissue penetration with enhanced synergistic effects through NIR-triggered light for cancer treatment.

Lanthanide-doped upconversion nanoparticles (UCNPs) possess the remarkable ability to convert multiple near-infrared (NIR) photons into higher energy ultraviolet-visible (UV-vis) photons, making them a prime candidate for several advanced applications within the realm of nanotechnology. Compared to traditional organic fluorophores and quantum dots (QDs), UCNPs possess narrower emission bands (fwhm of 10-50 nm), large anti-Stokes shifts, low toxicity, high chemical stability, and resistance to photobleaching and blinking. In addition, unlike UV-vis excitation, NIR excitation is nondestructive at lower power intensities and has high tissue penetration depths (up to 2 mm) with low autofluorescence and scattering. Together, these properties make UCNPs exceedingly favored for advanced bioanalytical and theranostic applications, where these systems have been well-explored. UCNPs are also well-suited for bioimaging, optically modulating chemistries, forensic science, and other state-of-the-art research applications. In this review, an up-to-date account of emerging applications in UCNP research, beyond bioanalytical and theranostics, are presented including optogenetics, super-resolution imaging, encoded barcodes, fingerprinting, NIR vision, UCNP-assisted photochemical manipulations, optical tweezers, 3D printing, lasing, NIR-II imaging, UCNP-molecule nanohybrids, and UCNP-based persistent luminescent nanocrystals.

Lanthanide-doped upconversion nanoparticles (UCNPs) are appealing for light emitting applications because their high internal conversion efficiency facilitates the amplified spontaneous emission (ASE) under low pumping. In addition, the integration of photonic crystals and microcavities with optical quantum emitters provides a unique opportunity to manipulate their light emissions and generate coherent light sources for quantum photonics. Here, this work describes a two-dimensional (2D) plasmonic lattice of Al nanocone array (Al NCA), which can confine the light at the tip. Light confinement by the enhancement effect supports narrow linewidth resonances as optical feedback for the ASE of UCNPs doped with sensitizer Yb 3+ ions/emitter Ho 3+ ions/relaxator Ce 3+ ions. An off-angle ASE with an enhancement of 19-fold from UCNPs is achieved by propagating lattice plasmons from the Al NCA. Moreover, this upconverting ASE can be switched on or off by adjusting the polarization state of the incident pump light, and photonic band engineering can be used to manipulate it intentionally. This composite plasmonic system opens prospective applications for the ASE as directional emission, real-time tunable wavelengths, controlled multimode lasing, and optical switches.

Lanthanide-doped upconversion nanoparticles (UCNPs) are rising as prospect nanomaterials for constructing polarization-sensitive narrowband near-infrared (NIR) photodetectors (PDs), which have attracted significant interest in astronomy, object identification, and remote sensing. However, polarized narrowband NIR photodetection and imaging based on UCNPs have yet to be realized. Herein, we demonstrate that NIR photodetection and imaging are capable of sensing polarized light as well as affording wavelength-selective detection at 1550 nm by integrating directional-Au@Ag nanorods (D-Au@Ag NRs) with NaYF 4 :Er 3+ @NaYF 4 UCNPs. Monolayer and large-area D-Au@Ag NRs polarization-sensitive plasmonic antenna films are obtained, and the center of their localized surface plasmon resonance (LSPR) peak is located at around 1550 nm. Experimental and theoretical results reveal that D-Au@Ag NRs have a sharp localized LSPR peak with a dominant scattering cross section. The UCNPs coupled with D-Au@Ag NRs exhibit significantly enhanced and strongly polarization-dependent luminescence with a high degree of polarization (DOP) of 0.72. The first polarization-resolved UC narrowband PD at 1550 nm is achieved, which delivers a DOP of 0.63, a detectivity of 1.69 × 10 10 Jones, and a responsivity of 0.32 A/W. Finally, we develop a polarized imaging system for 1550 nm with visual photoelectric detection based on the aforementioned PDs. Our work opens up possibilities for manipulating UC and developing next-generation polarization-sensitive narrowband infrared photodetection and imaging technology.

Engineering bacteria can achieve targeted and controllable cancer therapy using synthetic biology technology and the characteristics of tumor microenvironment. Besides, the accurate tumor diagnosis and visualization of the treatment process are also vital for bacterial therapy. In this paper, a light control engineered bacteria system based on upconversion nanoparticles (UCNP)-mediated time-resolved imaging (TRI) was constructed for colorectal cancer theranostic and therapy. UCNP with different luminous lifetimes were separately modified with the tumor targeting molecule (folic acid) or anaerobic bacteria (Nissle 1917, EcN) to realize the co-localization of tumor tissues, thus improving the diagnostic accuracy based on TRI. In addition, blue light was used to induce engineered bacteria (EcN-pDawn-φx174E/TRAIL) lysis and the release of tumor apoptosis-related inducing ligand (TRAIL), thus triggering tumor cell death. In vitro and in vivo results indicated that this system could achieve accurate tumor diagnosis and light-controlled cancer therapy. EcN-pDawn-φx174E/TRAIL with blue light irradiation could inhibit 53% of tumor growth in comparison to that without blue light irradiation (11.8%). We expect that this engineered bacteria system provides a new technology for intelligent bacterial therapy and the construction of cancer theranostics.

The utilizing light with broadband range has attracted lots of research interest for the photo induced reversible-deactivation radical polymerization (RDRP). However, it is still a challenge for a single catalyst to simultaneously respond to various lights with highly varied wavelengths. Here, we proposed a simple strategy for the preparation of a heterogeneous photocatalyst suitable for photo induced atom transfer radical polymerization (photoATRP) under full spectrum (from UV/vis light to NIR), by combining pyridine nitrogen doped carbon dots (N-CDs) and upconversion nanoparticles (UCNPs). In the presence of these robust UCNP@SiO 2 @N-CDs composite particles, the photoATRP could be carried on under the different irradiations of UV, blue, green, red, white, and 980 nm NIR light, with a low loading of part per million concentrations of the CuBr 2 /L catalyst. Moreover, the excellent solvent and aqueous compatibility allow UCNP@SiO 2 @N-CDs to be capable for photoATRP in both organic solvents and aqueous media, providing well-defined hydrophobic and hydrophilic polymers with low dispersity and excellent chain-end fidelity. In addition, the photoATRP with 980 nm NIR exhibited excellent penetrations through visible-light-proof barriers. The system could be used for the preparation of an injectable hydrogel that had dual curing and photoluminescence modes. Owing to the "living" characteristics of polymer chains achieved through ATRP, the hydrogel was capable to be easily repaired by using monomer as the binder.

Upconversion nanoparticles (UCNPs) and MnO 2 composite materials have broad prospects in biological applications due to their near-infrared (NIR) imaging capability and tumor microenvironment-responsive features. Nevertheless, the synthesis of such composite nanoplatforms still faces many hurdles such as redundant processing and uneven coatings. Here, we explored a simple, rapid, and universal method for precisely controlled coating of mesoporous MnO 2 (mMnO 2 ) using poly(ethylene imine) as a reducing agent and potassium permanganate as a manganese source. Using this strategy, a mMnO 2 shell was successfully coated on UCNPs. We further modified the mMnO 2 -coated UCNPs (UCNP@mMnO 2 ) with a photosensitizer (Ce6), cisplatin drug (DSP), and tumor targeting pentapeptide (TFA) to obtain a nanoplatform UCNP/Ce6@mMnO 2 /DSP-TFA for treating spinal metastasis of nonsmall cell lung cancer (NSCLC-SM). The utilization of both upconversion and downconversion luminescence of UCNPs with different NIR wavelengths can avoid the simultaneous initiation of NIR-II in vivo imaging and tumor photodynamic therapy, thus reducing damage to normal tissues. This platform achieved a high synergistic effect of photodynamic therapy and chemotherapy. This leads to beneficial antitumor effects on the therapy of NSCLC-SM.

Optical anticounterfeiting plays a vital role in information security because it can be recognized by the naked eye and is difficult to imitate. Herein, a hydrophilic modified upconversion nanoparticle (M-UCNP)-integrated bilayer inverse opal photonic crystal (IOPC) film was designed in which the luminescent M-UCNPs were deposited on the surface of the optimized bilayer structure with double photonic stop bands. The structure which can modulate light to produce structural colors can also enhance the upconversion luminescence (UCL) to improve the anticounterfeiting effect synergistically. On the one hand, the reflection colors from green to blue were observed in the specular angles on the front (540-layer) of the film. Meanwhile, the scattering colors under nonspecular angles from red to blue on the back (808-layer) appeared in the natural light. On the other hand, the bilayer structure in which the 808-layer functions as a "secondary excitation source" to improve the intensity of the excitation light on M-UCNPs and the 540-layer reflects the emission light of the M-UCNPs to enhance the UCL intensity endows the film with good night vision ability. Finally, the dual-mode structural colors and enhanced UCL of the patterned film work together to realize triple anticounterfeiting in banknotes.

Smart nanotheranostic systems (SNSs) have attracted extensive attention in antitumor therapy. Nevertheless, constructing SNSs with disease diagnosis ability, improved drug delivery efficiency, inherent imaging performance, and high treatment efficiency remains a scientific challenge. Herein, ultrasmall tin dioxide (SnO 2 ) was assembled with upconversion nanoparticles (UCNPs) to form mesoporous nanocapsules by an in situ hydrothermal deposition method, followed by loading with doxorubicin (DOX) and modification with bovine serum albumin (BSA). pH/near-infrared dual-responsive nanotheranostics was constructed for computed tomography (CT) and magnetic resonance (MR) imaging-induced collaborative cancer treatment. The mesoporous channel of SnO 2 was utilized as a reservoir to encapsulate DOX, an antineoplastic drug, for chemotherapy and as a semiconductor photosensitizer for photodynamic therapy (PDT). Furthermore, the DOX-loaded UCNPs@SnO 2 -BSA nanocapsules combined PDT, Nd 3+ -doped UCNP-triggered hyperthermia effect, and DOX-triggered chemotherapy simultaneously and demonstrated prominently enhanced treatment efficiency compared to the monotherapy model. Moreover, tin, as one of the trace elements in the human body, has a similar X-ray attenuation coefficient to iodine and therefore can act as a contrast agent for CT imaging to monitor the treatment process. Such an orchestrated synergistic anticancer treatment exhibited apparent inhibition of tumor growth in tumor-bearing mice with negligible side effects. Our study demonstrates nanocapsules with excellent biocompatibility and great potential for cancer treatment.

In situ quantification and imaging of low-level intracellular microRNAs (miRs) are important areas in biosensor research. Herein, DNA-driven Fe x Cu y Se@upconversion nanoparticle (UCNP) core@satellite nanostructures were developed to probe microRNA-21 (miR-21). Fe x Cu y Se@UCNP probes displayed dual signals: upconversion luminescence (UCL) and magnetic resonance imaging (MRI). In the presence of miR-21, the luminescence signal was restored and the T 2 value was significantly increased because of dissociation of UCNPs from the assemblies. There was a good linear relationship between the dual signals and the expression levels of miR-21 in the range of 0.035-31.824 amol/ng RNA . The limit of detection (LOD) was 0.0058 amol/ng RNA for the luminescence intensity and 0.0182 amol/ng RNA for the MRI signal. This method opens a new avenue for intracellular miR-21 detection with high sensitivity and specificity.

Photocatalytic artificial fixation of N 2 to NH 3 occurs over NaYF 4 :Yb,Tm (NYF) upconversion nanoparticles (NPs) decorated carbon nitride nanotubes with nitrogen vacancies (NYF/NV-CNNTs) in water under near-infrared (NIR) light irradiation. NYF NPs with a particle size of ca. 20 nm were uniformly distributed on the surface of NV-CNNTs. The NYF/NV-CNNTs with 15 wt % NYF exhibited the highest NH 3 production yield of 1.72 mmol L -1 g cat -1 , corresponding to an apparent quantum efficiency of 0.50% under NIR light illumination, and about three times higher the activity of the bare CNNTs under UV-filtered solar light. 15 N isotope-labeling NMR results confirm that the N source of ammonia originates from the photochemical N 2 reduction. The spectroelectrochemical measurements reveal that NVs can greatly facilitate the photogenerated electron transfer without energy loss, while the presence of NYF NPs shifts both the deep trap state and the edge of conduction band toward a lower potential. Moreover, NYF NPs endow the photocatalyst with a NIR light absorption via the fluorescence resonance energy transfer process, and NVs have the ability to enhance the active sites for a stronger adsorption of N 2 and decrease the surface quenching effect of NYF NPs, which thus can promote the energy migration within the heterojunctions. This work opens the way toward full solar spectrum photocatalysis for sustainable ammonia synthesis under aqueous system.

Two novel stimuli-responsive drug delivery systems (DDSs) were successfully created from bovine serum albumin- or myoglobin-gated upconversion nanoparticle-embedded mesoporous silica nanovehicles (UCNP@mSiO 2 ) via diselenide (Se-Se)-containing linkages. More importantly, multiple roles of each scaffold of the nanovehicles were achieved. The controlled release of the encapsulated drug doxorubicin (DOX) within the mesopores was activated by triple stimuli (acidic pH, glutathione, or H 2 O 2 ) of tumor microenvironments, owing to the conformation/surface charge changes in proteins or the reductive/oxidative cleavages of the Se-Se bonds. Upon release of DOX, the Förster resonance energy transfer between the UCNP cores and encapsulated DOX was eliminated, resulting in an increase in ratiometric upconversion luminescence for DOX release tracking in real time. The two protein-gated DDSs showed some differences in the drug release performances, relevant to structures and properties of the protein nanogates. The introduction of the Se-Se linkages not only increased the versatility of reductive/oxidative cleavages but also showed less cytotoxicity to all cell lines. The DOX-loaded protein-gated nanovehicles showed the inhibitory effect on tumor growth in tumor-bearing mice and negligible damage/toxicity to the normal tissues. The constructed nanovehicles in a spatiotemporally controlled manner have fascinating prospects in targeted drug delivery for cancer chemotherapy.

Parkinson's disease (PD) has been recently associated with the excessive expression of matrix metalloproteinase 3 (MMP3). One of the major challenges in treating PD is to effectively detect and inhibit the early MMP3 activities to relieve the neural stress and inflammation responses. Previously, numerous upconversion nanoparticle (UCNP)-based nanoprobes have been designed for the detection of biomarkers in neurodegenerative diseases. To further improve the performance of the conventional nanoprobes, we introduced novel reporting units and integrated the therapeutic reagents to fabricate a theragnostic platform for PD and other neurodegenerative diseases. Here, we designed a multifunctional UCNP/aggregation-induced emission luminogen (AIEgen)-based nanoprobe to effectively detect the time-lapse MMP3 activities in the inflammatory catecholaminergic SH-SY5Y cells and simultaneously deliver the MMP3-siRNA into the stressed catecholaminergic SH-SY5Y cells, inhibiting the MMP3-induced inflammatory neural responses. The unique features of our UCNP/AIEgen-based nanoprobe platform shed light on the development of a novel theragnostic probe for the early diagnosis and cure of neurodegenerative diseases.

It is highly desired to develop new antibacterial agents with superior bactericidal efficiency for minimizing the damage to biological cells. We developed a combined antibacterial nanohybrid exhibiting a superb bactericidal effect and excellent biocompatibility by integrating upconversion nanoparticles (UCNPs) with silver nanoclusters (AgNCs). UCNPs and methylene blue (MB) molecules were encapsulated with silica microspheres via microemulsion, with MB as the photosensitizer. Silver ions (Ag + ) were reduced by amino groups on the surface of silica spheres, wherein silver nanoclusters (AgNCs) were formed in situ to produce the nanohybrid, UCNPs@SiO 2 (MB)@AgNCs. UCNPs emit visible light at 655 nm under excitation by near-infrared radiation (NIR, 980 nm). MB absorbs the emission from UCNPs to generate toxic singlet oxygen ( 1 O 2 ), which leads to the apoptosis of bacteria cells. Meanwhile, silver ions released from AgNCs destroy the bacteria membrane structure. Upon NIR irradiation at 980 nm for 10 min, 8.33 μg mL -1 nanohybrid results in a 100% killing rate for both Gram-positive S. aureus (+) and Gram-negative E. coli (-).

Light-mediated remote control of stem cell fate, such as proliferation, differentiation, and migration, can bring a significant impact on stem cell biology and regenerative medicine. Current UV/vis-mediated control approaches are limited in terms of nonspecific absorption, poor tissue penetration, and phototoxicity. Upconversion nanoparticle (UCNP)-based near-infrared (NIR)-mediated control systems have gained increasing attention for vast applications with minimal nonspecific absorption, good penetration depth, and minimal phototoxicity from NIR excitations. Specifically, 808 nm NIR-responsive upconversion nanomaterials have shown clear advantages for biomedical applications owing to diminished heating effects and better tissue penetration. Herein, a novel 808 nm NIR-mediated control method for stem cell differentiation has been developed using multishell UCNPs, which are optimized for upconverting 808 nm NIR light to UV emission. The locally generated UV emissions further toggle photoswitching polymer capping ligands to achieve spatiotemporally controlled small-molecule release. More specifically, with 808 nm NIR excitation, stem cell differentiation factors can be released to guide neural stem cell (NSC) differentiation in a highly controlled manner. Given the challenges in stem cell behavior control, the developed 808 nm NIR-responsive UCNP-based approach to control stem cell differentiation can represent a new tool for studying single-molecule roles in stem cell and developmental biology.

In situ spatiotemporal microRNA (miRNA) imaging in mammal cells plays an essential role in illustrating its structures and biological functions. Herein, we proposed a near-infrared (NIR) light-activated nanoprobe for high-sensitive in situ controllable miRNA imaging in living cells. The NIR-activated nanoprobe employed an upconversion nanoparticle that acted as a NIR-to-UV transducer to trigger the following photocleavage toward a dumbbell DNA probe tethered on the surface of the nanoparticle. The structure change of the dumbbell probe then induced a catalytic hairpin assembly of target miRNAs, by which in situ readout of the amplified fluorescence signal was enabled. Additionally, both intracellular miRNA imaging and accurate quantification in live cells were realized without damaging the cell membranes. Compared with conventional in situ strategies, the proposed approach remarkedly increases imaging efficiency by eliminating those unfavored intercellular molecular imaging backgrounds. We assured that the proposed NIR-activated miRNA sensing strategy will add to the advancement for bioanalysis in living systems, which is of crucial importance in the diagnosis of various human diseases, especially cancers.

A desirable cancer therapeutic strategy is supposed to have effective ability to not only exert maximum anticancer ability but also inspire antitumor immunity for preventing tumor relapse and metastasis. During this research, multifunctional upconversion nanoparticles (UCNPs) coated by ROS-responsive micelles are prepared for tumor targeting and near-infrared (NIR)-triggered photodynamic therapy (PDT)-combined synergistic effect of chemotherapy. Moreover, both PDT and chemotherapy agents could activate antitumor immunity via inducing immunogenic cell death with CD8 + and CD4 + T cells infiltrating in tumors. Through the experiments, intravenous administration of multifunctional nanocarriers with noninvasive NIR irradiation destroys the orthotopic tumors and efficiently suppresses lung metastasis in a metastatic triple-negative breast cancer model by cascade-amplifying chemo-PDT and systemic antitumor immunity. In conclusion, this study provides prospective chemo-PDT with inspired antitumor immunity for metastatic cancer treatment.

The development of a highly effective photosensitizer (PS) that can be activated with a low-power single light is a pressing issue. Herein, we report a PS for synergistic photodynamic and photothermal therapy constructed through self-assembly of poly(selenoviologen) on the surface of core-shell NaYF 4 :Yb/Tm@NaYF 4 upconversion nanoparticles. The hybrid UCNPs/PSeV PS showed strong ROS generation ability and high photothermal conversion efficiency (∼52.5%) under the mildest reported-to-date irradiation conditions (λ = 980 nm, 150 mW/cm 2 , 4 min), leading to a high efficiency in killing methicillin-resistant Staphylococcus aureus (MRSA) both in vitro and in vivo . Remarkably, after intravenous injection, the reported PS accumulated preferentially in deep MRSA-infected tissues and achieved an excellent therapeutic index. This PS design realizes a low-power single-NIR light-triggered synergistic phototherapy and provides a simple and versatile strategy to develop safe clinically translatable agents for efficient treatment of deep tissue bacterial inflammations.

Though emerging as a promising therapeutic approach for cancers, the crucial challenge for photodynamic therapy (PDT) is activatable phototoxicity for selective cancer cell destruction with low "off-target" damage and simultaneous therapeutic effect prediction. Here, we design an upconversion nanoprobe for intracellular cathepsin B (CaB)-responsive PDT with in situ self-corrected therapeutic effect prediction. The upconversion nanoprobe is composed of multishelled upconversion nanoparticles (UCNPs) NaYF 4 :Gd@NaYF 4 :Er,Yb@NaYF 4 :Nd,Yb, which covalently modified with an antenna molecule 800CW for UCNPs luminance enhancement under NIR irradiation, photosensitizer Rose Bengal (RB) for PDT, Cy3 for therapeutic effect prediction, and CaB substrate peptide labeled with a QSY7 quencher. The energy of UCNPs emission at 540 nm is transferred to Cy3/RB and eventually quenched by QSY7 via two continuous luminance resonance energy transfer processes from interior UCNPs to its surface-extended QSY7. The intracellular CaB specifically cleaves peptide to release QSY7, which correspondingly activates RB with reactive oxygen species (ROS) generation for PDT and recovers Cy3 luminance for CaB imaging. UCNPs emission at 540 nm remains unchanged during the peptide cleavage process, which is served as an internal standard for Cy3 luminance correction, and the fluorescence intensity ratio of Cy3 over UCNPs (FI583/FI540) is measured for self-corrected therapeutic effect prediction. The proposed self-corrected upconversion nanoprobe implies significant potential in precise tumor therapy.

Peptides isolated from phage display libraries are powerful reagents for small-molecule immunoassay; however, their application as phage-borne peptides is significantly limited by the biological nature of the phage. Here, we present the use of lysine scaffold to prepare a series of different valence peptides to serve as replacements for phage-borne peptides. Benzothiostrobin was selected as a model analyte, the cyclic benzothiostrobin-peptidomimetic in the form of monomer, dendrimer-like dimer, and tetramer were designed and synthesized. Compared with the monomer, the affinity of dendrimer-like dimer and tetramer increased 1.87 and 13.6 times, respectively, as determined by isothermal titration calorimetry (ITC). A novel inner filter effect immunoassay (IFE-IA) with positive readout was developed for benzothiostrobin detection utilizing the peptidomimetics attached to upconversion nanoparticles (UCNPs) as energy donor and monoclonal antibody (mAb)-labeled urchin-like gold nanoflowers (AuNFs) as energy absorber, respectively. The sensitivity of the assay based on dendrimer-like tetramer was approximately 6 and 3 times higher than monomer and dendrimer-like dimer, respectively. After optimization, 50% saturation of the signal (SC 50 ) and detection range (SC 10 to SC 90 ) of the IFE-IA based on dendrimer-like tetramer were 11.81 ng mL -1 and 2.04-106.17 ng mL -1 , respectively. The IFE-IA also shows good accuracy for the detection of benzothiostrobin in authentic samples.

Herein, we developed a nanocomposite membrane with synergistic photodynamic therapy and photothermal therapy antibacterial effects, triggered by a single near-infrared (NIR) light illumination. First, upconversion nanoparticles (UCNPs) with a hierarchical structure (UCNPs@TiO 2 ) were synthesized, which use NaYF 4 :Yb,Tm nanorods as the core and TiO 2 nanoparticles as the outer shell. Then, nanosized graphene oxide (GO), as a photothermal agent, was doped into UCNPs@TiO 2 core-shell nanoparticles to obtain UCNPs@TiO 2 @GO. Afterward, the mixture of UCNPs@TiO 2 @GO in poly(vinylidene) fluoride (PVDF) was applied for electrospinning to generate the nanocomposite membrane (UTG-PVDF). Generation of reactive oxygen species (ROS) and changes of temperature triggered by NIR action were both investigated to evaluate the photodynamic and photothermal properties. Upon a single NIR light (980 nm) irradiation for 5 min, the nanocomposite membrane could simultaneously generate ROS and moderate temperature rise, triggering synergistic antibacterial effects against both Gram-positive and -negative bacteria, which are hard to be achieved by an individual photodynamic or photothermal nanocomposite membrane. Additionally, the as-prepared membrane can effectively restrain the inflammatory reaction and accelerate wound healing, thus exhibiting great potentials in treating infectious complications in wound healing progress.

Here, we have developed a new colorimetric and luminescence nanosensor, based on upconversion nanoparticles (UCNPs), for in vitro and ex vivo measurement of carbon monoxide (CO). The nanoprobe has two strong fluorescence emission peaks in the UCNP core to excite fluorophores at 540 and 800 nm. The CO-responsive palladium ion-bounded rhodamine B derivatives (Pd-RBDs) are encapsulated in the mesoporous silica (mSiO 2 ) shell and the particles outside the cyclodextrin (CD) layer. Reduction of palladium ions by CO results in the release of palladium from the Pd-RBDs, thereby inducing the closure of the spiro ring of the RBD and the accompanying reduction of rhodamine B (RB) absorption at 500-600 nm overlapping with the luminescence spectrum of UCNPs maximized at 540 nm. Therefore, the I 540 / I 800 ratio of the nanoprobe will increase when CO is present, making it possible to quantitatively measure CO. Besides working in a clean buffer environment with known [CO], this method was evaluated using living cells and tissue sections. Additionally, these probes were also successfully used to investigate the CO-related protective activity of anti-hepatic ischemia-reperfusion injury (HIRI) oligopeptides.

Herein, we report a siloxane-encapsulated upconversion nanoparticle hybrid composite (SE-UCNP), which exhibits excellent photoluminescence (PL) stability for over 40 days even at an elevated temperature, in high humidity, and in harsh chemicals. The SE-UCNP is synthesized through UV-induced free-radical polymerization of a sol-gel-derived UCNP-containing oligosiloxane resin (UCNP-oligosiloxane). The siloxane matrix with a random network structure by Si-O-Si bonds successfully encapsulates the UCNPs with chemical linkages between the siloxane matrix and organic ligands on UCNPs. This encapsulation results in surface passivation retaining the intrinsic fluorescent properties of UCNPs under severe conditions (e.g., 85 °C/85% relative humidity) and a wide range of pH (from 1 to 14). As an application example, we fabricate a two-color binary microbarcode based on SE-UCNP via a low-cost transfer printing process. Under near-infrared irradiation, the binary sequences in our barcode are readable enough to identify objects using a mobile phone camera. The hybridization of UCNPs with a siloxane matrix provides the capacity for highly stable UCNP-based applications in real environments.

Overdose of Cu 2+ is associated with multiple diseases, such as Wilson disease, Parkinson disease, and Alzheimer disease. Therefore, detections of Cu 2+ in vivo and in vitro are meaningful. Near-infrared fluorescent probes are commonly applied for the detection of Cu 2+ in real time. With mono detection signal provided, these probes are not persuasive when applied to complicated biological environments, such as cells and animals. In this report, we conjugated the organic fluorescent probe CYDAC 16 with the UCNPs (lanthanide-doped upconversion nanoparticles) to develop a ratiometric luminescent probe for Cu 2+ . The composite material UCNPs-CYDAC 16 provides a ratiometric signal based on an upconversion luminescence 660 and 800 nm. With good sensitivity and selectivity for Cu 2+ , it works well in vivo and in vitro for the detection of Cu 2+ . We believe it is promising in further biological applications.

Herein, a novel multifunctional nanoplatform was designed toward multimodality imaging and photothermal therapy (PTT). It was found that Bi nanoparticles could grow in situ on the surface of NaYF 4 :20%Yb,2%Er@NaYF 4 :40%Yb@NaGdF 4 core-shell nanoparticles (labeled as UCNPs). In this structure, UCNPs were mainly employed as an upconversion luminescence (UCL) imaging agent, whereas the Bi nanoparticles worked as an effective CT imaging and photothermal agent. Importantly, a dense SiO 2 shell was employed to protect the Bi nanoparticles from oxidation, and it also endowed the nanoplatform with excellent hydrophilic ability. The effective UCL/CT imaging and PTT performances were emphasized by a series of in vivo experiments, which suggest that the integrated nanoplatform with imaging and therapy functions shows great promise in the biomedical field.

The efficacy of dynamic therapy for solid tumors suffers daunting challenges induced by tumor hypoxia. Herein, we report a biocompatible nanosystem containing Fe(OH) 3 -modified upconversion nanoparticles (UCNPs) for promoting synergetic chemo- and photodynamic therapy with the modulation of tumor hypoxia. In this system, UCNPs convert 808 nm near-infrared excitation to visible photon energy, which stimulates chlorin-e6 photosensitizers to generate toxic reactive oxygen species (ROS) by consumption of dissolved oxygen in cancer cells. Importantly, we employ Fe(OH) 3 compounds to enable continuous oxygen generation in cancer cells and, meanwhile, induce extra ROS formation through the Fenton-like reaction. The system consequently improves the tumor treatment efficacy in vitro and in vivo. This study puts forward a novel combinatorial therapeutic platform for tumor microenvironment modulation and enhanced cancer therapy.

Photodynamic therapy (PDT) holds great promise as a noninvasive and selective cancer therapeutic treatment in preclinical research and clinical practice; however, it has limited efficacy in the ablation of deep-seated tumor because of hypoxia-associated circumstance and poor penetration of photosensitizers to cancer cells away from the blood vessels. To tackle the obstacles, we propose a therapeutic strategy that synergizes upconversion nanophotosensitizers (UNPSs) with hyperbaric oxygen (HBO) to remodel the extracellular matrix for enhanced photodynamic cancer therapy. The UNPSs are designed to have an Nd 3+ -sensitized sandwiched structure, wherein the upconversion core serves as light transducers to transfer energy to the neighboring photosensitizers to produce reactive oxygen species (ROS). With HBO, photodynamic process can generate abundant ROS in the intrinsically hypoxic tumor. It is revealed for the first time that HBO-assisted PDT decomposes collagen in the extracellular matrix of tumor and thus facilitates the diffusion of oxygen and penetration of UNPSs into the deeper area of tumor. Such a synergic effect eventually results in a significantly enhanced therapeutic efficacy at a low laser power density as compared with that using UNPSs alone. In view of its good biosafety, the HBO-assisted and UNPSs-mediated PDT provides new possibilities for treatment of solid tumors.

A new approach to encapsulating charged cargo molecules into a nanovector and subsequently using near-infrared (NIR) light to trigger the release is demonstrated. NIR light-responsive nanovector was prepared through electrostatic interaction-driven complexation between negatively charged silica-coated upconversion nanoparticles (UCNP@silica, 87 nm hydrodynamic diameter, polydispersity index ∼0.05) and a positively charged UV-labile polyelectrolyte bearing pendants of poly(ethylene glycol) and o-nitrobenzyl side groups; whereas charged fluorescein (FLU) was loaded through a co-complexation process. By controlling the amount of polyelectrolyte, UCNP@silica can be covered by the polymer, whereas remaining dispersed in aqueous solution. Under 980 nm laser excitation, UV light emitted by UCNP is absorbed by photolytic side groups within polyelectrolyte, which results in cleavage of o-nitrobenzyl groups and formation of carboxylic acid groups. Such NIR light-induced partial reversal of positive charge to negative charge on the polyelectrolyte layer disrupts the equilibrium among UCNP@silica, polyelectrolyte, and FLU and, consequently, leads to release of FLU molecules.

The efficacy of the conventional photodynamic therapy (PDT) is markedly suppressed by limited penetration depth of light in biological tissues and oxygen depletion in the hypoxic tumor microenvironment. Herein, mesoporous silica nanospheres with fine CaF 2 :Yb,Er upconversion nanocrystals entrapped in their porous structure are synthesized via a thermal decomposition method. After subsequently coating with a thin MnO 2 layer and loading with a photosensitizer, Chlorin e6 (Ce6), a new type of nanoscale PDT platform is obtained. Within such composite nanoparticles, Mn 2+ ions doped into the lattice of CaF 2 crystals effectively enhance the near-infrared (NIR)-triggered red-light upconversion photoluminescence for exciting the adsorbed Ce6 via resonance energy transfer, enabling the improved photodynamic phenomenon. Meanwhile, the MnO 2 coating modulates the hypoxic tumor microenvironment by in situ generating O 2 through the reaction with tumor endogenous H 2 O 2 . Both mechanisms acting synchronously lead to the superior therapeutic outcome in NIR-triggered photodynamic tumor therapy.

Common photosensitizers used in photodynamic therapy do not penetrate the skin effectively. In addition, the visible blue and red lights used to excite such photosensitizers have shallow penetration depths through tissue. To overcome these limitations, we have synthesized ultraviolet- and visible-light-emitting, energy-transfer-based upconversion nanoparticles and coencapsulated them inside PLGA-PEG (methoxy poly(ethylene glycol)-b-poly(lactic-co-glycolic acid)) nanoparticles with the photosensitizer protoporphyrin IX. Nd 3+ has been introduced as a sensitizer in the upconversion nanostructure to allow its excitation at 808 nm. The subcytotoxic doses of the hybrid nanoparticles have been evaluated on different cell lines (i.e., fibroblasts, HaCaT, THP-1 monocytic cell line, U251MG (glioblastoma cell line), and mMSCs (murine mesenchymal stem cells). Upon NIR (near infrared)-light excitation, the upconversion nanoparticles emitted UV and VIS light, which consequently activated the generation of reactive-oxygen species (ROS). In addition, after irradiating at 808 nm, the resulting hybrid nanoparticles containing both upconversion nanoparticles and protoporphyrin IX generated 3.4 times more ROS than PLGA-PEG nanoparticles containing just the same dose of protoporphyrin IX. Their photodynamic effect was also assayed on different cell cultures, demonstrating their efficacy in selectively killing treated and irradiated cells. Compared to the topical application of the free photosensitizer, enhanced skin permeation and penetration were observed for the nanoparticulate formulation, using an ex vivo human-skin-permeation experiment. Whereas free protoporphyrin IX remained located at the outer layer of the skin, nanoparticle-encapsulated protoporphyrin IX was able to penetrate through the epidermal layer slightly into the dermis.

Photoinduced reversible addition-fragmentation chain transfer (RAFT) polymerization generally adopts high-energy ultraviolet (UV) or blue light. In combination with photoredox catalyst, the excitation light wavelength was extended to the visible and even near-infrared (NIR) region for photoinduced electron transfer RAFT polymerization. In this report, we introduce for the first time a surface NIR-light-initiated RAFT polymerization on upconversion nanoparticles (UCNPs) without adding any photocatalyst and construct a functional inorganic core/polymer shell nanohybrid for application in cancer theranostics. The multilayer core-shell UCNPs (NaYF 4 :Yb/Tm@NaYbF 4 :Gd@NaNdF 4 :Yb@NaYF 4 ), with surface anchorings of chain transfer agents, can serve as efficient NIR-to-UV light transducers for initiating the RAFT polymerization. A hierarchical double block copolymer brush, consisting of poly(acrylic acid) (PAA) and poly(oligo(ethylene oxide)methacrylate-co-2-(2-methoxy-ethoxy)ethyl methacrylate) (PEG for short), was grafted from the surface in sequence. The targeting arginine-glycine-aspartic (RGD) peptide was modified at the end of the copolymer through the trithiolcarbonate end group. After loading of doxorubicin, the UCNPs@PAA-b-PEG-RGD exhibited an enhanced U87MG cancer cell uptake efficiency and cytotoxicity. Besides, the unique upconversion luminescence of the nanohybrids was used for the autofluoresence-free cell imaging and labeling. Therefore, our strategy verified that UCNPs could efficiently activate RAFT polymerization by NIR photoirradiation and construct the complex nanohybrids, exhibiting prospective biomedical applications due to the low phototoxicity and deep penetration of NIR light.

Photodynamic therapy (PDT) is an auspicious strategy for cancer therapy by yielding reactive oxygen species (ROS) under light irradiation. Here, we have developed near-infrared (NIR) triggered polymer encapsulated upconversion nanoparticles (UCNPs) based on aggregation-induced emission (AIE) characteristics and mitochondria target ability for PDT. The coated AIE polymer as a photosensitizer can be photoactivated by the up-converted energy of UCNPs upon 980 nm laser irradiation, which could generate ROS efficiently in mitochondria and induce cell apoptosis. Moreover, a "sheddable" poly(ethylene glycol) (PEG) layer was easily conjugated at the surface of NPs. The pH-responsive PEG layer shields the surface positive charges and shows stronger protein-resistance ability. In the acidic tumor environment, PEGylated NPs lose the PEG layer and show the mitochondria-targeting ability by responding to tumor acidity. A cytotoxicity study indicated that these NPs have good biocompatibility in the dark but exert severe cytotoxicity to cancer cells, with only 10% cell viability, upon being irradiated with an NIR laser. The AIE nanoparticles are a good candidate for effective mitochondria targeting photosensitizer for PDT.

Methylammonium lead halide perovskite has emerged as a new class of low-temperature-processed high-performance semiconductors for optoelectronics, but with photoresponse limited to the UV-visible region and low environmental stability. Herein, we report a flexible planar photodetector based on MAPbI 3 microarrays integrated with NaYF 4 :Yb/Er upconversion nanoparticles (UCns) that offers promise for future high performance and long-term environmental stability. The promise derives from the confluence of several factors, including significantly enhanced photons absorption in the visible spectrum, efficient energy transition in the near-infrared (NIR) region, and inhibition of water attack by the hydrophobic UCns capping layer. The UCns layer aided in remarkably enhanced photodetection capability in the visible spectrum with detectivity (D*) reaching 5.9 × 10 12 Jones, among the highest reported values, due to the increased photocarrier lifetime and decreased reflectivity. Excellent NIR photoresponse with spectral responsivity (R) and D* as high as 0.27 A W -1 and 0.76 × 10 12 Jones were obtained at 980 nm, respectively, superior to the reported values of state-of-the-art organic-perovskite NIR photodetectors. Moreover, the hydrophobic UCns capping layer serving as a moisture inhibitor allowed significantly enhanced long-term environmental stability, e.g., 70% vs 27% performance retained after 1000 h exposure in 30-40% RH humidity air without encapsulation for the bilayer and the neat MAPbI 3 devices, respectively. These results suggest that the composite based on perovskite and UCns is promising for constructing high-performance broadband optoelectronic devices with long-term stability.

Upconversional core-shell nanostructures have gained considerable attention due to their distinct enhanced fluorescence efficiency, multifunctionality, and specific applications. Recently, we have developed a sequential growth process to fabricate unique upconversion core-shell nanoparticles. Time evolution of morphology for the NaYF 4 :Yb/Er@NaGdF 4 nanodumbbells has been extensively investigated. An Ostwald ripening growth mechanism has been proposed to illustrate the formation of NaYF 4 :Yb/Er@NaGdF 4 nanodumbbells. The hydrophilic NaYF 4 :Yb/Er@NaGdF 4 core-shell nanodumbbells exhibited strong upconversion fluorescence and showed higher magnetic resonance longitudinal relaxivity (r 1 = 7.81 mM -1 s -1 ) than commercial contrast agents (Gd-DTPA). NaYF 4 :Yb/Er@NaGdF 4 nanodumbbells can serve as good candidates for high efficiency fluorescence and magnetic resonance imaging.

Development of multidrug resistance (MDR) contributes to the majority of treatment failures in clinical chemotherapy. We report facial layer-by-layer engineered upconversion nanoparticles (UCNPs) for near-infrared (NIR)-initiated tracking and delivery of small interfering RNA (siRNA) to enhance chemotherapy efficacy by silencing the MDR1 gene and resensitizing resistant ovarian cancer cells to drug. Layer-by-layer engineered UCNPs were loaded with MDR1 gene-silencing siRNA (MDR1-siRNA) by electrostatic interaction. The delivery vehicle enhances MDR1-siRNA cellular uptake, protects MDR1-siRNA from nuclease degradation, and promotes endosomal escape for silencing the MDR gene. The intrinsic photon upconversion of UCNPs provides an unprecedented opportunity for monitoring intracellular attachment and release of MDR1-siRNA by NIR-initiated fluorescence resonance energy transfer occurs between donor UCNPs and acceptor fluorescence dye-labeled MDR1-siRNA. Enhanced chemotherapeutic efficacy in vitro was demonstrated by cell viability assay. The developed delivery vehicle holds great potential in delivery and imaging-guided tracking of therapeutic gene targets for effective treatment of drug-resistant cancers.

Bioimaging probes have been extensive studied for many years, while it is still a challenge to further improve the image quality for precise diagnosis in clinical medicine. Here, monodisperse NaGdF 4 :Yb 3+ ,Tm 3+ ,x% Bi 3+ (abbreviated as GYT-x% Bi 3+ , x = 0, 5, 10, 15, 20, 25, 30) upconversion nanoparticles (UCNPs) have been prepared through the solvothermal method. The near-infrared upconversion emission intensity of GYT-25% Bi 3+ has been enhanced remarkably than that of NaGdF 4 :Yb 3+ ,Tm 3+ (GYT) with a factor of ∼60. Especially, the near-infrared upconversion emission band centered at 802 nm is 150 times stronger than the blue emission band of GYT-25% Bi 3+ UCNPs. Such high ratio of NIR/blue UCL intensity could reduce the damage to tissues in the bioimaging process. The possibility of using GYT-25% Bi 3+ UCNPs with strong near-infrared upconversion emission for optical imaging in vitro and in vivo was performed. Encouragingly, the UCL imaging penetration depth can be achieved as deep as 20 mm. Importantly, GYT-25% Bi 3+ UCNPs exhibit a much higher X-ray computed tomography (CT) contrast efficiency than GYT and iodine-based contrast agent under the same clinical conditions, due to the high X-ray attenuation coefficient of bismuth. Hence, simultaneous remarkable enhancement of NIR emission and X-ray CT signal in upconversion nanoparticles could be achieved by optimizing the doping concentration of Bi 3+ ions. Additionally, Gd 3+ ions in the UCNPs endow GYT-25% Bi 3+ UCNPs with T 1 -weighted magnetic resonance (MR) imaging capability.

A near-infrared-driven photoelectrochemical aptasensor was developed as a new method for the detection of the breast cancer cell MCF-7. The upconversion nanoparticles and TiO 2 /CdTe heterostructure were combined to prepare the film electrode, and the high-affinity aptamer AS1411 was conjugated to the electrode to recognize MCF-7 cells. In this fabrication, the upconversion nanoparticles transferred the near-infrared light to visible light, which could excite the semiconductor to enhance the current response. As a result, the aptasensor revealed good sensitivity and specificity with MCF-7 cell concentrations ranging from 1 × 10 3 to 1 × 10 5 cells/mL. The results presented a favorable determination of MCF-7 cells, which was achieved with the help of the upconversion nanoparticles and the photoelectrochemical interface.

The treatment depth of existing photodynamic therapy (PDT) is limited because of the absorption of visible excitation light in biological tissue. It can be augmented by means of upconversion nanoparticles (UCNPs) transforming deep-penetrating near-infrared (NIR) light to visible light, exciting PDT drugs. We report here a facile strategy to assemble such PDT nanocomposites functionalized for cancer targeting, based on coating of the UCNPs with a silica layer encapsulating the Rose Bengal photosensitizer and bioconjugation to antibodies through a bifunctional fusion protein consisting of a solid-binding peptide linker genetically fused to Streptococcus Protein G'. The fusion protein (Linker-Protein G) mediates the functionalization of silica-coated UCNPs with cancer cell antibodies, allowing for specific target recognition and delivery. The resulting nanocomposites were shown to target cancer cells specifically, generate intracellular reactive oxygen species under 980 nm excitation, and induce NIR-triggered phototoxicity to suppress cancer cell growth in vitro.

Novel core-shell-shell structured nanoparticles 75 nm in diameter with all-in-one "smart" functional capabilities for simultaneous photoresponsive drug release, photodynamic therapy, and cell imaging are designed and prepared. These nanoparticles consist of an upconversion (UC) emission core, a photosensitizer-embodied silica sandwich shell, and a β-cyclodextrin (β-CD) gated mesoporous silica outmost shell with drugs (Rhodamine B as a model) loaded inside. We show in this proof-of-concept demonstration that, under 980 nm near-infrared irradiation, UC 540 nm green light emissions were emitted for cell imaging, and 660 nm red light emissions were excited for activating photosensitizers to generate singlet oxygen, which could be exploited directly to kill cancer cells and simultaneously dissociate β-CD gatekeeper to release drugs. The preliminary results reported here will shed new light on the future design and applications of multifunctional platforms for cancer therapy and diagnostic.

Novel flower-like α-NaYb(Mn)F4:Er(3+)/Tm(3+)@NaYF4 upconversion nanoparticles (UCNPs) as luminescent nanothermometers have been developed by combining liquid-solid solution hydrothermal strategy with thermal decomposition strategy. Under 980 nm excitation, they exhibit intense upconversion luminescence and temperature-dependent upconversion luminescence over a wide temperature range. The influence of temperature on "band-shape" upconversion luminescence (UCL) spectra and the intensity of emission bands are analyzed and discussed in detail. We further successfully test and verify that intensity ratios REr of (2)H11/2 → (4)I15/2 and (4)S3/2 → (4)I15/2 and RTm of (1)G4 → (3)H5 and (3)H4 → (3)H6 are sensitive to temperature, and the population of active ions follows Boltzmann-type population distribution very well. These luminescent nanothermometers could be applied over a wide temperature range from 123 to 423 K with high sensitivity, which enable them to be excellent candidates for temperature sensors.

Multimodal bioimaging nanoparticles by integrating diverse imaging ingredients into one system, represent a class of emerging advanced materials that provide more comprehensive and accurate clinical diagnostics than conventional contrast agents. Here monodisperse and biocompatible core-shell nanoparticles, NaGdF4: Yb(3+)/Er(3+)@NaGdF4:Nd@sodium-gluconate (termed as GNa-Er@Nd), with about 26 nm in diameter were successfully prepared by a facile two step reactions in high boiling solvents, and followed a ligand exchange process with sodium gluconate. The resulting GNa-Er@Nd nanoparticles were well characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared spectra (FTIR), and zeta potentials. These nanohybrids present brightly dual-wavelength excited upconversion luminescence (UCL) under both 980 and 793 nm laser because of the synergistic effect of Yb(3+)/Er(3+) and Nd(3+). They also exhibited excellent relaxivity parameters (r1) in magnetic resonance imaging (MRI) and Hounsfield units (HU) in X-ray computed tomography (CT) that are comparable to the clinical contrast agents. Therefore, these small and monodisperse nanoparticles provide options to construct a unique platform for potential multimodal UCL/CT/MRI imaging simultaneously.

In this work we demonstrate a DNA biosensor based on fluorescence resonance energy transfer (FRET) between NaYF4:Yb,Er nanoparticles and graphene oxide (GO). Monodisperse NaYF4:Yb,Er nanoparticles with a mean diameter of 29.1 ± 2.2 nm were synthesized and coated with a SiO2 shell of 11 nm, which allowed the attachment of single strands of DNA. When these DNA-functionalized NaYF4:Yb,Er@SiO2 nanoparticles were in the proximity of the GO surface, the π-π stacking interaction between the nucleobases of the DNA and the sp(2) carbons of the GO induced a FRET fluorescence quenching due to the overlap of the fluorescence emission of the NaYF4:Yb,Er@SiO2 and the absorption spectrum of GO. By contrast, in the presence of the complementary DNA strands, the hybridization leads to double-stranded DNA that does not interact with the GO surface, and thus the NaYF4:Yb,Er@SiO2 nanoparticles remain unquenched and fluorescent. The high sensitivity and specificity of this sensor introduces a new method for the detection of DNA with a detection limit of 5 pM.

A novel core-shell structure based on upconversion fluorescent nanoparticles (UCNPs) and dopamine-melanin has been developed for evaluation of the antioxidant capacity of biological fluids. In this approach, dopamine-melanin nanoshells facilely formed on the surface of UCNPs act as ultraefficient quenchers for upconversion fluorescence, contributing to a photoinduced electron-transfer mechanism. This spontaneous oxidative polymerization of the dopamine-induced quenching effect could be effectively prevented by the presence of various antioxidants (typically biothiols, ascorbic acid (Vitamin C), and Trolox). The chemical response of the UCNPs@dopamine-melanin hybrid system exhibited great selectivity and sensitivity toward antioxidants relative to other compounds at 100-fold higher concentration. A satisfactory correlation was established between the ratio of the "anti-quenching" fluorescence intensity and the concentration of antioxidants. Besides the response of the upconversion fluorescence signal, a specific evaluation process for antioxidants could be visualized by the color change from colorless to dark gray accompanied by the spontaneous oxidation of dopamine. The near-infrared (NIR)-excited UCNP-based antioxidant capacity assay platform was further used to evaluate the antioxidant capacity of cell extracts and human plasma, and satisfactory sensitivity, repeatability, and recovery rate were obtained. This approach features easy preparation, fluorescence/visual dual mode detection, high specificity to antioxidants, and enhanced sensitivity with NIR excitation, showing great potential for screening and quantitative evaluation of antioxidants in biological systems.