Surface Of Upconversion Nanoparticles Research Articles

Upconversion nanoparticles-CuMnO2 nanoassemblies for NIR-excited imaging of reactive oxygen species in vivo

Here, we designed a ratiometric luminescent nanoprobe based on lanthanide-doped upconversion nanoparticles-CuMnO2 nanoassemblies for rapid and sensitive detection of reactive oxygen species (ROS) levels in living cells and mouse. CuMnO2 nanosheets exhibit a wide absorption range of 300–700 nm, overlapping with the visible-light emission of upconversion nanoparticles (UCNPs), resulting in a significant upconversion luminescence quenching. In an acidic environment, H2O2 can promote the redox reaction of CuMnO2, leading to its dissociation from the surface of UCNPs and the restoration of upconversion luminescence. The variation in luminescence intensity ratio (UCL475/UCL450) were monitored to detect ROS levels. The H2O2 nanoprobe exhibited a linear response in the range of 0.314–10 μM with a detection limit of 11.3 nM. The biological tests proved the excellent biocompatibility and low toxicity of obtained UCNPs-CuMnO2 nanoassemblies. This ratiometric luminescent nanoprobe was successfully applied for the detection of exogenous and endogenous ROS in live cells as well as in vivo ROS quantitation. The dual transition metal ions endow this probe efficient catalytic decomposition capabilities, and this sensing strategy broadens the application of UCNPs-based nanomaterials in the field of biological analysis and diagnosis.

Dye-sensitized lanthanide-doped upconversion nanoprobe for enhanced sensitive detection of Fe3+ in human serum and tap water

Iron ion (Fe3+) detection is crucial for human health since it plays a crucial role in many physiological activities. In this work, a novel Schiff-base functionalized cyanine derivative (CyPy) was synthesized, which was successfully assembled on the surface of upconversion nanoparticles (UCNPs) through an amphiphilic polymer encapsulation method. In the as-designed nanoprobe, CyPy, a recognizer of Fe3+, is served as energy donor and β-NaYF4:Yb,Er upconversion nanoparticles are adopted as energy acceptor. As a result, a 93-fold enhancement of upconversion luminescence is achieved. The efficient energy transfer from CyPy to β-NaYF4:Yb,Er endows the nanoprobe a high sensitivity for Fe3+ in water with a low detection limit of 0.21 μM. Moreover, the nanoprobe has been successfully applied for Fe3+ determination in human serum and tap water samples with recovery ranges of 95 %-105 % and 97 %-106 %, respectively. Moreover, their relative standard deviations are all below 3.72 %. This work provides a sensitive and efficient methodology for Fe3+ detection in clinical and environmental testing.

Construction of UCNPs-aptamer-AuNPs luminescence energy transfer probe for ratio detection of Staphylococcus aureus.

A ratio luminescence probe was developed for detecting Staphylococcus aureus (S. aureus) based on luminescence energy transfer (LET) using double-wavelength emission (550 nm and 812 nm) upconversion nanoparticles (UCNPs) as donor, gold nanoparticles (AuNPs) as acceptor and the aptamer for S. aureus as the specific recognition and link unit. The LET process could cause luminescence quenching because of the spectral overlap between the acceptor and the donor at 550 nm. In the presence of S. aureus, S. aureus selectively combined with the aptamer, and the AuNPs left the surface of UCNPs, which weakened the quenching effect and restored the luminescence of UCNPs. Based on this, the ratio detection was realized by monitoring the change of the luminescence signal of the probe at 550 nm and taking the luminescence signal at 812 nm as the reference signal. Crucially, the probe has a fast reaction speed, with a reaction time of 25 min, and the detection of S. aureus is realized in the concentration range of 5.0 × 103-3.0 × 105 CFU/ml, with the detection limit of 106 CFU/ml. Therefore, the ratio probe has great potential for detecting of S. aureus in food because of its high sensitivity, fast speed and good selectivity.

“Integrated diagnosis and treatment” of upconversion nanocomposite hydrogel for osteoarthritis treatment

Osteoarthritis (OA) is a common degenerative joint disease for which there is no definitive treatment. Mesenchymal stem cells (MSCs) can be differentiated into many types of cells such as chondrocytes, which have been used for OA treatment. How to keep the cell viability and promote the chondrogenic differentiation after MSCs transplantation into the knee joint cavityiscrucial. In this study, upconversion nanocomposite hydrogel was developed for integrated diagnosis and treatment of OA. The Er doped core–shell upconversion nanoparticles (UCNPs) were synthesized first and coated on mesoporous silica (UCNP@mSiO2). Then, an H2O2-sensitive thioketal (TK) linker (MAL-PEG-TK-NHS) was attached to the UCNP@mSiO2 surface to link capsular β-cyclodextrin (NH2-β-CD) and black hole quencher (NH2-BHQ3) to form functionalized UCNPs. After loading the drug kartogenin (KGN) that can induce chondrogenic differentiation of MSCs, the UCNP/KGN nanocomposites were mixed with VitroGel to formed the upconversion nanocomposite hydrogel (UCNP/VitroGel). The UCNP/VitroGel could allow MSCs to be implanted well and maintain good survival in vitro. In the presence of hydrogen peroxide (H2O2), the TK bond breakage and triggered release BHQ to recover the fluorescence of UCNPs for ROS detection, and the β-CD also left from the surface of UCNPs to release KGN for inducing the chondrogenic differentiation of MSCs. Thus, the UCNP/VitroGel could detect the ROS after inject into the knee joint cavity for OA diagnosis first via the fluorescence recovery of UCNPs under the 980 nm near-infrared light. And then the KGN release from UCNP/KGN nanocomposites in the environment of OA to induce the chondrogenic differentiation of MSCs for the treatment of OA. This UCNP/VitroGel will be a powerful tool for “integrated diagnosis and treatment” of OA.

Unlabelled LRET biosensor based on double-stranded DNA for the detection of anthraquinone anticancer drugs.

Based on upconversion nanoparticles (UCNPs) as energy donor and herring sperm DNA (hsDNA) as molecular recognition element, an unlabelled upconversion luminescence (UCL) affinity biosensor was constructed for the detection of anthraquinone (AQ) anticancer drugs in biological fluids. AQ anticancer drugs can insert into the double helix structure of hsDNA on the surface of UCNPs, thereby shortening the distance from UCNPs. Therefore, the luminescence resonance energy transfer (LRET) phenomenon is effectively triggered between UCNPs and AQ anticancer drugs. Hence, AQ anticancer drugs can be quantitatively detected according to the UCL quenching rate. The biosensor showed good sensitivity and stability for the detection of daunorubicin (DNR) and doxorubicin (ADM). For the detection of DNR, the linear range is 1-100 μg·mL-1 with a limit of detection (LOD) of 0.60 μg·mL-1, and for ADM, the linear range is 0.5-100 μg·mL-1 with a LOD of 0.38 μg·mL-1. The proposed biosensor provides a convenient method for monitoring AQ anticancer drugs in clinical biological fluids in the future.

Salinomycin and IR780-loaded upconversion nanoparticles influence biological behavior of liver cancer stem cells by persistently activating the MAPK signaling pathway

The combination of chemotherapy and phototherapy has emerged as a promising therapeutic approach for enhancing the efficacy of cancer treatment and mitigating drug resistance. Salinomycin (SAL), a polyether antibiotic, exhibits potent cytotoxicity against chemotherapy-resistant cancer cells. IR780 iodide, a novel photosensitive reagent with excellent near-infrared (NIR) light absorption and photothermal conversion abilities, is suitable for use in photothermal therapy for cancers. However, both SAL and IR780 exhibit hydrophobic properties that limit their clinical applicability. Upconversion nanoparticles (UCNPs) are an emerging class of fluorescent probe materials capable of emitting high-energy photons upon excitation by low-energy NIR light. The UCNPs not only function as nanocarriers for drug delivery but also serve as light transducers to activate photosensitizers for deep-tissue photodynamic therapy. Here, to enhance the targeting and bioavailability of hydrophobic drugs in liver cancer stem cells (LCSCs), we employ distearoyl phosphorethanolamine-polyethylene glycol (DSPE-PEG) to encapsulate SAL and IR780 on the surface of UCNPs. Cell viability was evaluated using the CCK-8 assay. Cell migration was assessed by the Transwell Boyden Chamber. The activation of the mitogen-activated protein kinase (MAPK) signaling pathway was measured via western blot. The results demonstrated successful loading of both IR780 and SAL onto the UCNPs, and the SAL and IR780-loaded UCNPs (UISP) exhibited a robust photothermal effect under NIR light irradiation. The UISP effectively inhibited the viability of HCCLM3 and LCSCs. Under NIR light irradiation, the UISP further suppressed HCCLM3 viability but had no impact on LCSC viability; however, it could further inhibit LCSC migration. Meanwhile, under NIR light irradiation, the UISP persistently activated the MAPK pathway more significantly in LCSCs. These findings suggest that exposure to NIR light results in persistent activation of the MAPK pathway by UISP, thereby influencing the biological behavior of LCSCs and enhancing their therapeutic efficacy against liver cancer.

Robust Strategy to Improve the Compatibility between Incorporated Upconversion Nanoparticles and the Bulk Transparent Polymer Matrix.

Traditional transparent polymer nanocomposites combined with functional fluorescent inorganic nanofillers are promising for many advanced optical applications. However, the aggregation of the incorporated functional nanoparticles results in light scattering and will decrease the transparency of nanocomposites, which will restrain the application of the transparent nanocomposites. Herein, a robust synthesis strategy was proposed to modify upconversion nanoparticles (UCNPs) with polymethyl methacrylate (PMMA) to form UCNP@PMMA core@shell nanocomposites though metal-free photoinduced surface-initiated atom transfer radical polymerization (photo-SI-ATRP), and thus, the dispersity of UCNP@PMMA and the interface compatibility between the surface of UCNPs and the bulk PMMA matrix was greatly improved. The obtained PMMA nanocomposites possess high transparency and show strong upconversion photoluminescence properties, which promises great opportunities for application in 3D display and related optoelectronic fields. This strategy could also be applied to fabricate other kinds of functional transparent polymer nanocomposites with inorganic nanoparticles uniformly dispersed.

Triplet-Induced Singlet Oxygen Photobleaches Near-Infrared Dye-Sensitized Upconversion Nanosystems.

The rapid photobleaching of near-infrared (NIR) dye-sensitized upconversion nanosystems is one of the crucial problems that has blocked their technological applications. Uncovering the photophysical and photochemical pathways of NIR dyes would help to elucidate the photobleaching mechanism and thereby improve the photostability of the system. Here we investigate the triplet dynamics of NIR dyes and their interaction with triplet oxygen in the typically investigated IR806-sensitized upconversion nanoparticle (UCNP) nanosystem. Low-temperature fluorescence at 77 K provides direct proof of the generation of singlet oxygen (1O2) under 808 nm laser irradiation. Mass spectrometry indicates that all three double bonds in the structure of IR806 can be broken in the photochemical process. Coupling IR806 to the surface of UCNPs can accelerate its triplet dynamics, thus producing more 1O2 to photocleave IR806. Importantly, we find that the addition of β-carotene can scavenge the generated 1O2, thereby providing a simple method to effectively inhibit photobleaching.

Upconversion nanoparticle-based fluorescence resonance energy transfer sensing platform for the detection of cathepsin B activity in vitro and in vivo.

A simple fluorescence resonance energy transfer (FRET) sensing platform (termed as USP), comprised of upconversion nanoparticles (UCNPs) as the energy donor and Cy5 as the energy acceptor, has been synthesized for cathepsin B (CTSB) activity detection in vitro and in vivo. When Cy5-modified peptide substrate (peptide-Cy5) of CTSB is covalently linked on the surface of UCNPs, the FRET between the UCNPs (excitation: 980nm; emission: 541nm/655nm) and Cy5 (excitation: 645nm) leads to a reduction in the red upconversion luminescence (UCL) signal intensity of UCNPs. Cy5 can be liberated from UCNPs in the presence of CTSB through the cleavage of peptide-Cy5 by CTSB, leading to the recovery of the red UCL signal of UCNPs. Because the green UCL signal of UCNPs remains constant during the CTSB digestion, it can be considered as an internal reference. The findings demonstrate the ability of USP to detect CTSB with the linear detection ranges of 1 to 100ng·mL-1 in buffer and 2 × 103 to 1 × 105 cells in 0.2mL cell lysates. The limits of detection (LODs) are 0.30ng·mL-1 in buffer and 887 cells in 0.2mL of cell lysates (S/N = 3). The viability of USP to detect CTSB activity in tumor-bearing mice is hasfurtherbeen investigated using in vivo fluorescent imaging.

Biomimetic Biomembrane Encapsulation and Targeted Delivery of a Nitric Oxide Release Platform for Therapy of Parkinson's Disease.

The existence of the blood-brain barrier (BBB) and the complex inflammatory environment in the brain are two major obstacles in the treatment of Parkinson's disease (PD). As a target group, we modified the red blood cell membrane (RBCM) on the surface of upconversion nanoparticles (UCNPs) in this study to effectively target the brain. Mesoporous silicon, coated with UCNPs (UCM), was loaded with S-nitrosoglutathione (GSNO) as the nitric oxide (NO) donor. Then, UCNPs were excited to emit green light (540 nm) by 980 nm near-infrared (NIR). In addition, it produced a light-responsive anti-inflammatory effect by promoting the release of NO from GSNO and lowering the brain's level of proinflammatory factors. A series of experiments demonstrated that this strategy could effectively mitigate the inflammatory response damage of neurons in the brain.

Specific and Long-Term Luminescent Monitoring of Hydrogen Peroxide in Tumor Metastasis.

Luminescent monitoring of endogenous hydrogen peroxide (H2 O2 ) in tumors is conducive to understanding metastasis and developing novel therapeutics. The clinical transformation is obstructed by the limited light penetration depth, toxicity of nano-probes, and lack of long-term monitoring modes of up to days or months. New monitoring modes are introduced via specific probes and implantable devices, which can achieve real-time monitoring with a readout frequency of 0.01 s or long-term monitoring for months to years. Near-infrared dye-sensitized upconversion nanoparticles (UCNPs) are fabricated as the luminescent probes, and the specificity to reactive oxygen species is subtly regulated by the self-assembled monolayers on the surfaces of UCNPs. Combined with the passive implanted system, a 20-day monitoring of H2 O2 in the rat model of ovarian cancer with peritoneal metastasis is achieved, in which the limited light penetration depth and toxicity of nano-probes are circumvented. The developed monitoring modes show great potential in accelerating the clinical transformation of nano-probes and biochemical detection methods.

Near-infrared light triggered in situ release of CO for enhanced therapy of glioblastoma

BackgroundPhotodynamic therapy (PDT) features high biocompatibility and high spatiotemporal selectivity, showing a great potential in glioblastoma (GBM) treatment. However, its application was restricted by the poor therapeutic efficacy and side effect.ResultsIn this study, a therapeutic nanoplatform (UCNPs@Ce6/3HBQ@CM) with combination of PDT and CO therapy was constructed, in which a photoCORM and a photosensitizer were loaded onto the surface of upconversion nanoparticles (UCNPs) functioning as photon transducer. Benefitting from NIR excitation and multicolor emission of UCNPs, the penetration depth of excitation light is enhanced and meanwhile simultaneous generation of CO and ROS in tumor site can be achieved. The as-prepared nanocomposite possessed an elevated therapeutic efficiency with the assistance of CO through influencing mitochondrial respiration and depleting ATP, accompanying with the reduced inflammatory responses. By wrapping a homologous cell membrane, the nanocomposite can target GBM and accumulate in the tumor site, affording a powerful tool for precise and efficient treatment of GBM.ConclusionThis therapeutic nanoplatform UCNPs@Ce6/3HBQ@CM, which combines PDT and CO therapy enables precise and efficient treatment of refractory glioblastoma.

Upconversion nanoparticle-based optogenetic nanosystem for photodynamic therapy and cascade gene therapy.

Most photosensitizer molecules used for the photodynamic therapy (PDT) are chemically-synthesized organic photosensitizer dyes which show several limitations such as unsatisfactory cell uptake, weak selectivity and off-target phototoxicity. Recently, genetically-encoded photosensitizers have attracted increasing attentions which provide the targeted cell elimination with single-cell precision. However, their applications are mainly limited by the shallow tissue penetration depth of the excitation light and the low cell apoptosis ratio. Herein, we developed a feasible upconversion nanoparticle (UCNP)-based optogenetic nanosystem with three-in-one functional integration: bio-imaging, NIR-triggered PDT and cascade gene therapy. Firstly, the mitochondria-targeted genetically-encoded photosensitizer was constructed and transfected into cancer cells. Then, the functional upconversion nanoprobe was constructed with the mitochondria targetability and then the siRNA was loaded on the surface of UCNPs via the reactive oxygen species (ROSs) sensitive chemical bond. After the transfection and incubation, both of the upconversion nanoprobe and the genetically-encoded photosensitizer were accumulated in the mitochondria of cancer cells. Under the NIR irradiation, the emission of UCNPs could excite the expressed protein photosensitizer to generate ROSs which then stimulated the release of siRNAs in a controllable manner, achieving PDT and cascade gene therapy. Since the generation of ROSs and the release of siRNA occurred in the mitochondria in-situ, the mitochondria-mediated cell apoptosis signal pathway would be activated to induce cell apoptosis and subsequently inhibit tumor growth. To the best of our knowledge, this is the first report about NIR laser-activated, organelle-localized genetically-encoded photosensitizers developed for cascade therapy, which will widen the application of optogenetic tools in the tumor therapy. STATEMENT OF SIGNIFICANCE: The application of genetically-encoded photosensitizers in photodynamic therapy (PDT) is mainly limited by the shallow tissue penetration depth of the excitation light and unsatisfactory therapeutic performance. In this experiment, we developed an upconversion nanoparticles-based optogenetic nanosystem to enhance the PDT and cascade gene therapy for malignant tumors. The expressed genetically-encoded photosensitizers were accumulated in the mitochondria, which were activated in situ by the upconversion nanoprobe. Besides, the photogenerated reactive oxygen species (ROSs) stimulated the release of siRNAs in a controllable manner. To the best of our knowledge, this is the first report about NIR laser-activated, genetically-encoded photosensitizers developed for organelle-localized controllable cascade therapy. We hope this work can accelerate the application of genetically-encoded photosensitizers in the tumor therapy.

A DNA-based nanodevice for near-infrared light-controlled drug release and bioimaging

DNA-based nanostructures have shown curative potential in drug delivery and anti-tumor therapy. However, the applications of such systems are limited by the lack of precise control over the space and duration of drug release. Here, we report a near-infrared (NIR) light-guided DNA nanodevice that enables controlled drug release for precise tumor imaging and therapy. The DNA nanodevice is constructed by engineering GC-rich DNA duplexes with an ultraviolet (UV) light labile moiety and further modification onto the surface of upconversion nanoparticles (UCNPs). The chemotherapeutic drug (doxorubicin, Dox) is intercalated into the GC motif of DNA duplexes, where the fluorescence signal of Dox is markedly quenched. Upon NIR light irradiation, the UCNPs acting as energy transducers emit UV light that can break the photolabile moiety in DNA duplexes, resulting in the controlled release of Dox and recovery of their fluorescence signal. We present that this DNA nanodevice is not only able to selectively induce tumor cells apoptosis via NIR light-mediated activation, but also enables in situ imaging and monitoring of drug release. Therefore, this modular strategy opens a window for remotely controlled drug delivery.

Dual excitable upconversion nanoparticle@polydopamine nanocomposite with intense red emission and efficient photothermal generation

Integration of strong upconversion emission with deep tissue penetration and stable photothermal generation is of great significance for imaging-guided photothermal therapy under infrared excitation. Herein, the NaYF4:Yb3+,Ho3+,Ce3+@NaGdF4:Yb3+,Nd3+@NaGdF4 core-shell-shell upconversion nanoparticles (UCNPs) with increasing Ce3+ doping concentration were firstly synthesized, in which the size manipulation, enhanced red to green emission intensity ratio (IR/IG), 980 and 808 nm dual-modal excitations, as well as improved total upconversion emission intensity can be achieved. After the coating of polydopamine (PDA) through dopamine spontaneous polymerization on the UCNPs surface under alkaline condition, the obtained UCNP@PDA nanocomposites show efficient photothermal effect under 808 nm excitation, while the thickness variation of PDA can be indicated by the upconversion spectra under 980 nm excitation. Interestingly, the photothermal effect of the UCNP@PDA nanocomposites with high IR/IG ratio is more stable with PDA thickness variation, which benefits from the structure design that allows PDA to simultaneously absorb the visible emission from inside UCNPs and the external 808 nm infrared light. Further in vitro cytotoxicity assay and photothermal therapy demonstrate that the UCNP@PDA nanocomposite has good biocompatibility and ability to kill tumor cells by photothermal effect under 808 nm excitation. This research may provide a nanoplatform for integrating deep bioimaging with highly stable photothermal therapy without the sacrifice of radiative transitions of rare earth ions.

The Surface Charge of Polymer-Coated Upconversion Nanoparticles Determines Protein Corona Properties and Cell Recognition in Serum Solutions.

Applications of nanoparticles (NPs) in the life sciences require control over their properties in protein-rich biological fluids, as an NP quickly acquires a layer of proteins on the surface, forming the so-called "protein corona" (PC). Understanding the composition and kinetics of the PC at the molecular level is of considerable importance for controlling NP interaction with cells. Here, we present a systematic study of hard PC formation on the surface of upconversion nanoparticles (UCNPs) coated with positively-charged polyethyleneimine (PEI) and negatively-charged poly (acrylic acid) (PAA) polymers in serum-supplemented cell culture medium. The rationale behind the choice of UCNP is two-fold: UCNP represents a convenient model of NP with a size ranging from 5 nm to >200 nm, while the unique photoluminescent properties of UCNP enable direct observation of the PC formation, which may provide new insight into this complex process. The non-linear optical properties of UCNP were utilised for direct observation of PC formation by means of fluorescence correlation spectroscopy. Our findings indicated that the charge of the surface polymer coating was the key factor for the formation of PC on UCNPs, with an ensuing effect on the NP-cell interactions.

Lysosomal Adenosine Triphosphate-Activated Upconversion Nanoparticle/Carbon Dot Composite for Ratiometric Imaging of Hepatotoxicity.

Drug-induced hepatotoxicity (DIH) is a common cause of acute liver injury, endangering human health. Intracellular adenosine triphosphate (ATP) content in hepatocytes is related to hepatotoxicity. Thus, monitoring the dynamic changes in lysosomal ATP is promising to further understand the pathogenesis and accurate evaluation of DIH. Herein, we developed a lysosomal ATP-activated upconversion nanoprobe by decorating ATP-sensitive carbon dots (CDs) on the surface of upconversion nanoparticles (UCNPs) for ratiometric imaging of hepatotoxicity. Owing to the excellent optical characteristics of UCNPs as well as the high selectivity and biocompatibility of CDs, this nanoprobe showed robust reversibility and good sensitivity to ATP in an acidic environment. Noticeably, it was successfully applied in imaging the lysosomal ATP levels fluctuation in living cells and deep tissues and used for studying the production and remediation pathways of acetaminophen-induced hepatotoxicity. This nanoprobe is significant for further understanding the pathogenesis of DIH and may be a potentially effective tool for the clinical evaluation of DIH.

Efficient ROS activation by highly stabilized aqueous ICG encapsulated upconversion nanoparticles for tumor cell imaging and therapeutics

Dye-sensitized upconversion nanoparticles (UCNPs) have gained significant interest in biological applications. However, previous attempts to utilize these dye-sensitized UCNPs in the aqueous environment suffer from dramatic decline in the upconversion luminescence (UCL) intensity and problems with nanoparticles aggregation and water quenching. By employing indocyanine green (ICG) as a hydrophobic amplifier and energy harvester for UCNPs, we use a general, facile, and kinetically controlled mixing technology—flash nanoprecipitation (FNP)—to prepare aqueous stable ICG-sensitized UCNPs encapsulated by a biocompatible block copolymer poly (ethylene glycol)-b-poly (lactic-co-glycolic acid (PEG-b-PLGA) to efficiently activate ROS generation for simultaneous cancer cell imaging and treatment. As compared to NPs obtained from traditional drip and stir method (TM), the NPs under high turbulent conditions (high Re) exhibit smaller size, narrower size distribution, and much higher stability, for the UCNPs hydrophobicity enhanced by ICG which was bound on the surface of UCNPs due to the coordination effect between sulfonates of ICG molecules and naked lanthanide metal ions of UCNPs. The remained UCL intensity was significantly boosted as well as ROS generation through FNP in the presence of ICG, but not for TM samples indicating superior protection of upconversion NPs from water quenching and the energy transfer between ICG and UCNP was well retained. The efficiency of ROS generation of NPs via FNP evidently increases with the stronger red-light emission of UCNPs, resulting in high cytotoxicity for SMMC-7721 cells in vitro and good suppression of tumor growth in vivo. The success of NPs by FNP in biological application demonstrates a bright prospect of FNP for synthesis of efficient antitumor nanoparticles.

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

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

Binary Ligand‐Mediated Photochromic Tuning of Lanthanide‐Doped Upconversion Nanoparticle Conjugates

AbstractThe ability to tune photochromic features of nanoparticle (NP)‐ligand conjugates can vastly extend the utility of dynamic materials in the fields of drug delivery, bioimaging, and data storage. Herein, the photochromic tuning of lanthanide‐doped upconversion nanoparticle (UCNP)‐spiropyran (SP) conjugates through a binary ligand strategy is reported. It is found that the content of SP ligand on the surface of UCNPs can be rationally controlled by an SP‐to‐oleate ligand exchange reaction, allowing for regulating the steric congestion in the ligand layer. A highly congested SP layer not only leads to an ultralong lifetime for the purple open‐ring state but also results in improved red fluorescence under UV excitation. The enhancement in steric congestion further enables increased activation energy for the ring‐opening reaction for the bound SP ligand, permitting the generation of high‐resolution self‐erasing patterns in a UCNP‐SP conjugate‐doped polydimethylsiloxane film by local irradiation with either UV or near‐infrared light. The findings provide new insights into the optical tuning of nanoconjugates by controlling the conformational dynamics of their mixed ligand layers.