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To resolve the problem of target specificity and light transmission to deep-seated tissues in photodynamic therapy (PDT), we report a cancer cell-targeted photosensitizer using photoprotein-conjugated upconversion nanoparticles (UCNPs) with high target specificity and efficient light transmission to deep tissues. Core-shell UCNPs with low internal energy back transfer were conjugated with recombinant proteins that consists of a photosensitizer (KillerRed; KR) and a cancer cell-targeted lead peptide (LP). Under near infrared (NIR)-irradiating condition, the UCNP-KR-LP generated superoxide anion radicals as reactive oxygen species via NIR-to-green light conversion and exhibited excellent specificity to target cancer cells through receptor-mediated cell adhesion. Consequently, this photosensitizing process facilitated rapid cell death in cancer cell lines (MCF-7, MDA-MB-231, and U-87MG) overexpressing integrin beta 1 (ITGB1) receptors but not in a cell line (SK-BR-3) with reduced ITGB1 expression and a non-invasive normal breast cell line (MCF-10A). In contrast to green light irradiation, NIR light irradiation exhibited significant PDT efficacy in cancer cells located beneath porcine skin tissues up to a depth of 10 mm, as well as in vivo tumor xenograft mouse models. This finding suggests that the designed nanocomposite is useful for sensing and targeting various deep-seated tumors. [ABSTRACT FROM AUTHOR]

Near-infrared (NIR) light-induced photothermal therapy (PTT) has become a new method for precise tumor treatment due to its non-invasive, low toxicity, and targeted treatment. Gold nanoparticles have become an ideal photothermal agents due to its unique surface plasmon resonance (SPR), efficient photothermal conversion efficiency, low biological toxicity and good photostability. High quality imaging technology is a reliable and powerful tool for achieving effective photothermal therapy, especially multimodal imaging technology, which has excellent performance compared to a single imaging method, providing the possibility for more comprehensive and accurate tumor imaging, thereby significantly improving the potential of non-invasive medical treatment. Owing to their rich 4f electronic structure, NIR light excited rare-earth doped upconversion nanoparticles (UCNPs) exhibit multifunctional properties such as magnetism, fluorescence, X-ray attenuation, and radiation, making them an important application prospect in multimodal imaging as contrast agents. Therefore, constructing NIR-induced Au NPs/UCNPs composite nanosystems for multimodal imaging-guided photothermal therapy is expected to become a new strategy for cancer diagnosis and treatment. In this paper, we briefly introduced the optical properties of Au and UCNPs. In addition, this paper reviewed the latest research progress of PTT research on NIR induced UCNPs Au (nanoshell, nanorod, nanoclusters) composite nano system under the guidance of visual fluorescence imaging. The future prospects for achieving integrated diagnosis and treatment are presented, providing new ideas for its further research, development, and clinical application. [ABSTRACT FROM AUTHOR]

In an attempt to achieve antitumor effects by switching the phenotype of macrophages from the tumor-promoting M2 type to the tumor-suppressing M1 type, we fabricated mannose-decorated/macrophage membrane–coated, silica-layered NaErF 4 @NaLuF 4 upconverting nanoparticles (UCNPs) co-doped with perfluorocarbon (PFC)/chlorin e6 (Ce6) and loaded with paclitaxel (PTX) (UCNP@mSiO 2 -PFC/Ce6@RAW-Man/PTX: ∼61 nm; −11.6 mV). These nanoparticles were designed to have two major functionalities, (i) efficient singlet oxygen generation aided by an oxygen supply and (ii) good targeting to tumor-associated macrophage (TAMs) (M2-type), to induce polarization to M1 type macrophages that release proinflammatory cytokines and suppress breast cancers. The primary UCNPs consisted of lanthanide elements (erbium and lutetium) in a core@shell structure, and they facilely emitted 660 nm light in response to a deep-penetrating 808 nm near-infrared laser. Moreover, the UCNPs@mSiO 2 -PFC/Ce6@RAW-Man/PTX were able to release O 2 and generate 1O 2 because of the co-doped PFC/Ce6 and upconversion. Our nanocarriers' excellent uptake to RAW 264.7 macrophage cells (M2 type) and efficient M1-type polarization activity were clearly demonstrated using qRT-PCR and immunofluorescence-based confocal laser scanning microscopy. Our nanocarriers displayed significant cytotoxicity to 4T1 cells in 2D culture and 3D co-culture systems of 4T1/RAW 264.7 cells. More importantly, UCNPs@mSiO 2 -PFC/Ce6@RAW-Man/PTX (+808 nm laser) noticeably suppressed tumor growth in 4T1-xenografted mice, compared with the other treatment groups (332.4 vs. 709.5–1185.5 mm3). We attribute this antitumor efficacy to the prominent M1-type macrophage polarization caused by our nanocarriers through efficient ROS/O 2 generation and targeting of M2-type TAMs via mannose ligands on coated macrophage-membrane. [Display omitted] [ABSTRACT FROM AUTHOR]

Controlled drug delivery holds great potential for effective tumor treatment owing to the merits of overcoming drug resistance and improving therapeutic efficacy while minimizing systemic toxicity. However, accurate and controllable delivery of chemotherapeutics into tumor tissue with high efficiency remains a huge challenge. Taking advantage of the UV-emitting characteristics of upconversion nanoparticles (UCNPs), herein we for the first time in-situ immobilization (ENDDI) system that is fabricated by decorating UCNPs with MMP-2 responsive and photocrosslinkable peptide bearing anticancer drug doxorubicin (DOX) for overcoming multidrug resistance. Upon cleavage with tumor-specific MMP-2, the peptide fragment containing a photolabile benzophenone (BP) and DOX could be released and in-situ immobilized within the tumor through the covalent crosslinking reaction between BP and neighboring biomolecules under the excitation of converted UV emission from UCNPs, which remarkably blocks the exocytosis of DOX leading to prolonged drug retention, achieving significant suppression of DOX-resistant breast tumors. Our current dual stimuli-mediated sequential drug delivery and in-situ immobilization represent a generalizable strategy for the effective treatment of multidrug resistant tumors. [ABSTRACT FROM AUTHOR]

Skin wounds are particularly susceptible to bacterial infection, which seriously affects skin healing. Therefore, wound dressing with antibacterial properties is urgently needed for skin trauma treatment. Here, we have designed a hydrogel dressing by utilizing a multilayered upconversion nanocomposite that is constructed by the upconversion nanoparticles (UCNPs) coated with a mesoporous silica-loaded zinc phthalocyanine (ZnPc) photosensitizer. The nanocomposite can produce singlet oxygen for photodynamic therapy under 980 nm excitation by luminescent energy resonance transfer between UCNPs and ZnPc, which endows the antibacterial activity during the wound healing process. Furthermore, by utilizing the non-toxic active ester of polyethylene glycol as the cross-linking agent, the nanocomposite is assembled in chitosan to generate the hydrogel dressing, whereas chitosan is considered an ideal material for promoting wound healing. The experiments show that the dressing has good antimicrobial activity against Staphylococcus aureus and Escherichia coli. Meanwhile, in vivo experiments demonstrate that the antibacterial hydrogel dressing can effectively reduce inflammation and significantly accelerate wound healing due to its low toxicity, deep tissue penetration, good biocompatibility, and strong antibacterial capacity. Such a photodynamic hydrogel dressing designed here would provide a practical application pathway for photodynamic sterilization and treating emergencies as a total solution. [ABSTRACT FROM AUTHOR]

Upconverting stimulated emission depletion microscopy (U‐STED) is emerging as an effective approach for super‐resolution imaging due to its significantly low depletion power and its ability to surpass the limitations of the square‐root law and achieve higher resolution. Though the compelling performance, a trade‐off between the spatial resolution and imaging quality in U‐STED has been recognized in restricting the usability due to the low excitation power drove high depletion efficiency. Moreover, it is a burden to search for the right power relying on trial and error as the underpinning mechanism is unknown. Here, a method is proposed that can easily predict the ideal excitation power for high depletion efficiency with the assistance of the non‐saturate excitation based on the dynamic cross‐relaxation (CR) energy transfer of upconversion nanoparticles. This allows the authors to employ the rate equation model to simulate the populations of each relevant energy state of lanthanides and predict the ideal excitation power for high depletion efficiency. The authors demonstrate that the resolution of STED with the assistance of nonsaturated confocal super‐resolution results can easily achieve the highest resolution of sub‐40 nm, 1/24th of the excitation wavelengths. The finding on the CR effect provides opportunities for population control in realizing low‐power high‐resolution nanoscopy. [ABSTRACT FROM AUTHOR]

Frontiers in theranostics are driving the demand for multifunctional nanoagents. Upconversion nanoparticle (UCNP)-based systems activated by near-infrared (NIR) light deeply penetrating biotissue are a powerful tool for the simultaneous diagnosis and therapy of cancer. The intercalation into large polymer micelles of poly(maleic anhydride-alt-1-octadecene) provided the creation of biocompatible UCNPs. The intrinsic properties of UCNPs (core@shell structure NaYF4:Yb3+/Tm3+@NaYF4) embedded in micelles delivered NIR-to-NIR visualization, photothermal therapy, and high drug capacity. Further surface modification of micelles with a thermosensitive polymer (poly-N-vinylcaprolactam) exhibiting a conformation transition provided gradual drug (doxorubicin) release. In addition, the decoration of UCNP micelles with Ag nanoparticles (Ag NPs) synthesized in situ by silver ion reduction enhanced the cytotoxicity of micelles at cell growth temperature. Cell viability assessment on Sk-Br-3, MDA-MB-231, and WI-26 cell lines confirmed this effect. The efficiency of the prepared UCNP complex was evaluated in vivo by Sk-Br-3 xenograft regression in mice for 25 days after peritumoral injection and photoactivation of the lesions with NIR light. The designed polymer micelles hold promise as a photoactivated theranostic agent with quattro-functionalities (NIR absorption, photothermal effect, Ag NP cytotoxicity, and Dox loading) that provides imaging along with chemo- and photothermal therapy enhanced with Ag NPs. [ABSTRACT FROM AUTHOR]

A highly structured fluorometric bioassay has been proposed for screening Staphylococcus aureus (S. aureus). The study exploits (i) the spectral attributes of the hexagonal NaYF4:Yb,Er upconversion nanoparticle (UCNP)-coated 3-aminopropyl)triethoxysilane; (ii) the intrinsic non-fluorescent quenching features of the highly stable dark blackberry (BBQ®-650) receptor; (iii) the aptamer (Apt-) biorecognition and binding affinity, and (iv) the complementary DNA hybridizer-linkage efficacy. The principle relied on the excited state energy transfer between the donor Apt-labeled NH2-UCNPs at the 3′ end, and cDNA-grafted BBQ®-650 at the 5′ end, as the effective receptors. The donor moieties in proximity (< 10.0 nm) trigger hybridization with the cDNA-grafted dark BBQ®-650, as the receptors of energy from the 2F5/2 level of Yb3+ ions to initiate the Förster resonance energy transfer pathway. This was confirmed by the decline in the excited-state lifetimes from 223.52 μs (τ1) to 179.26 μs (τ2). The existence of the target S. aureus in the bioassay attracts the Apt- resulting in the detachment of the acceptor, and disintegration of the complex configuration via conformation reversal. The re-activated fluorescence monitored at λex/em = 980/652 nm, as a function of the logarithmic concentration of S. aureus (42 to 4.2 × 108 CFU mL−1), yielded an ultra-low detection response of 2.0 CFU mL−1. The bioassay screening of S. aureus in real samples revealed satisfactory recoveries (92.44–107.82%) and validation results (p > 0.05). Hence, the comprehensive Apt-labeled NH2-UCNPs-cDNA-grafted dark BBQ®-650 bioassay offered fast and precise S. aureus screening in food and environmental settings. [ABSTRACT FROM AUTHOR]

• The whole assay process can be completed within 15 min. • We used a one-step reaction to complete the conversion of oil-phase UCNPs to aqueous-phase UCNP-COOH within 2 h by the carboxyl polymer embedding method. • Our t-PSA UCNPs strip has excellent accuracy, anti-interference and stability in the clinical gray zone (4–10 ng/mL) of PSA clinical application. • It is a portable analytical tool suitable for on-site analysis and rapid screening. • We validated this UCNP PSA strip in a large-scale clinical sample of 1397 patients, showing good consistency with the Roche chemiluminescence kit. Prostate specific antigen (PSA) is a widely-used biomarker for the diagnosis, screening, and prognosis of prostate cancer (PCa). It is critical to develop a rapid and convenient method to accurately detect PSA levels, especially when the PSA levels are in the clinical gray area of 4–10 ng/mL. We developed a novel upconversion nanoparticle (UCNP)-based fluorescence lateral flow test strip for qualitatively and quantitatively detecting PSA. The carboxyl group-modified UCNPs (UCNP-COOH) were labeled with anti-PSA antibodies via 1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) as labeling probes to recognize PSA. The fluorescence intensity of the UCNP-probe was then measured with a laser fluorescence scanner. A total of 1397 serum and 20 fingertip blood samples were collected to validate the UCNP strip. A reliable correlation between the area ratio (TC), reflecting the fluorescence intensity of the test/control line, and the PSA concentration was observed (r = 0.9986). The dose-dependent luminescence enhancement showed good linearity in the PSA concentration range from 0.1 to 100.0 ng/mL with a detection limit of 0.1 ng/mL. Our UCNP POCT strip demonstrated excellent accuracy, anti-interference and stability in the gray zone (4–10 ng/mL) of PSA clinical application and outperformed other PSA test strips. The UCNP strip showed good consistency with the Roche chemiluminescence assay in 1397 serum samples. It also showed good performance for PSA detection using fingertip blood samples. This novel UCNP-based test strip could be a sensitive and reliable POCT assay to detect PSA, facilitating the diagnosis and surveillance of PCa. [ABSTRACT FROM AUTHOR]

Developing a feasible way to feature longitudinal (T 1) and transverse (T 2) relaxation performance of contrast agents for magnetic resonance imaging (MRI) is important in cancer diagnosis and therapy. Improved accessibility to water molecule is essential for accelerating the relaxation rate of water protons around the contrast agents. Ferrocenyl compounds have reversible redox property for modulating the hydrophobicity/hydrophilicity of assemblies. Thus, they could be the candidates that can change water accessibility to the contrast agent surface. Herein, we incorporated ferrocenylseleno compound (FcSe) with Gd3+-based paramagnetic UCNPs, to obtain FNPs-Gd nanocomposites using T 1 −T 2 MR/UCL trimodal imaging and simultaneous photo-Fenton therapy. When the surface of NaGdF 4 :Yb,Tm UNCPs was ligated by FcSe , the hydrogen bonding between hydrophilic selenium and surrounding water molecules accelerated their proton exchange to initially endow FNPs-Gd with high r 1 relaxivity. Then, hydrogen nuclei from FcSe disrupted the homogeneity of the magnetic field around the water molecules. This facilitated T 2 relaxation and resulted in enhanced r 2 relaxivity. Notably, upon the near-infrared light-promoted Fenton-like reaction in the tumor microenvironment, hydrophobic ferrocene(II) of FcSe was oxidized into hydrophilic ferrocenium(III), which further increased the relaxation rate of water protons to obtain r 1 = 1.90±0.12 mM−1 s−1 and r 2 = 12.80±0.60 mM−1 s−1. With an ideal relaxivity ratio (r 2 /r 1) of 6.74, FNPs-Gd exhibited high contrast potential of T 1 −T 2 dual-mode MRI in vitro and in vivo. This work confirms that ferrocene and selenium are effective boosters that enhance the T 1 −T 2 relaxivities of MRI contrast agents, which could provide a new strategy for multimodal imaging-guided photo-Fenton therapy of tumors. T 1 −T 2 dual-mode MRI nanoplatform with tumor-microenvironment-responsive features has been an attractive prospect. Herein, we designed redox ferrocenylseleno compound (FcSe) modified paramagnetic Gd3+-based UCNPs, to modulate T 1 −T 2 relaxation time for multimodal imaging and H 2 O 2 -responsive photo-Fenton therapy. Selenium−hydrogen bond of FcSe with surrounding water molecules facilitated water accessibility for fast T 1 relaxation. Hydrogen nucleus in FcSe perturbed the phase coherence of water molecules in an inhomogeneous magnetic field and thus accelerated T 2 relaxation. In tumor microenvironment, FcSe was oxidized into hydrophilic ferrocenium via NIR light-promoted Fenton-like reaction which further increased both T 1 and T 2 relaxation rates; Meanwhile, the released toxic •OH performed on-demand cancer therapy. This work confirms that FcSe is an effective redox mediate for multimodal imaging-guided cancer therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Preeclampsia is a heterogeneous and multiorgan cardiovascular disorder of pregnancy. Here, we report the development of a novel strip‐based lateral flow assay (LFA) using lanthanide‐doped upconversion nanoparticles conjugated to antibodies targeting two different biomarkers for detection of preeclampsia. We first measured circulating plasma FKBPL and CD44 protein concentrations from individuals with early‐onset preeclampsia (EOPE), using ELISA. We confirmed that the CD44/FKBPL ratio is reduced in EOPE with a good diagnostic potential. Using our rapid LFA prototypes, we achieved an improved lower limit of detection: 10 pg ml−1 for FKBPL and 15 pg ml−1 for CD44, which is more than one order lower than the standard ELISA method. Using clinical samples, a cut‐off value of 1.24 for CD44/FKBPL ratio provided positive predictive value of 100 % and the negative predictive value of 91 %. Our LFA shows promise as a rapid and highly sensitive point‐of‐care test for preeclampsia. [ABSTRACT FROM AUTHOR]

The synergistic influence of synthesized MoS2 (syn-MoS2) nanosheets and NaYF4:Yb,Tm,Nd upconversion nanoparticles (UCNP) on effective dye degradation is demonstrated. A detailed characterization of bulk MoS2 (b-MoS2), syn-MoS2 (with enhanced photocatalytic activity compared to the commercially available b-MoS2), and UCNP was done. Optical properties revealed that emission spectra of UCNP corresponding to 450, 475, and 650 nm overlap with absorption spectra of MoS2 (∼455 and 635 nm). A comparative methylene blue degradation of 96% could be achieved with the combination of UCNP and syn-MoS2 in comparison to 56.4% for syn-MoS2 and 42% for b-MoS2. Concentration-dependent dye degradation study of UCNP and syn-MoS2 revealed a maximum dye removal efficiency of 99.6% for 150 mg L–1 of syn-MoS2 and 200 mg L–1 of UCNP within 2 hrs. Comparative degradation investigations were performed on various dyes (methylene blue, methylene orange, rhodamine B, and their mixture) and water systems (artificial river-water and artificial seawater) to assess the potential applicability of the system in environmental remediation. After five cycles of reusability studies, an efficacy of 88% dye removal was obtained. The mechanism behind this was investigated using the ESR and scavengers test, which confirmed that the primary radicals responsible for dye degradation were superoxide (•O2–) and hydroxyl (•OH). A comparative photocurrent experiment also verified that the presence of UCNP enhances the efficiency of the syn-MoS2 by 98% in the presence of visible light. [ABSTRACT FROM AUTHOR]

The growing crisis of antibiotic resistance calls for advanced and sustainable antibacterial strategies. In the past few years, lanthanide‐doped upconversion nanoparticles (UCNPs) with unique photophysical properties have been innovatively explored for bacterial detection and therapy, and hold promise for alleviating challenges faced in the post‐antibiotic era. In this review, the interface engineering for the bacteria‐targeted UCNP nanoplatforms is highlighted, the principles and merits of various upconversion detection strategies are discussed, and the latest progress in UCNP‐based antibacterial applications are summarized, especially in deep‐tissue infection imaging and therapy. Finally, the remaining concerns and future efforts for practical applications are put forward. This review is expected to provide comprehensive guidance for diagnosing and combating bacterial infections based on advanced UCNP nanoplatforms. [ABSTRACT FROM AUTHOR]

Integrating biocompatible metal–organic frameworks (MOFs) with upconversion nanoparticles (UCNPs), capable of converting near‐infrared (NIR) light into visible or ultraviolet emissions, affords unique UCNPs@MOFs heterostructures for nanomedicine. Alongside inherited advantages from parent UCNPs on imaging and parent MOFs with porous structure on chemodrugs delivery, upconversion Förster resonance energy transfer (FRET) from UCNPs to molecular moieties in MOFs offers unique abilities to probe or modulate intracellular and tumor microenvironments at high spatiotemporal precision. As a result, UCNPs@MOFs heterostructures allow to detect hint number of biomolecules, regulate intracellular ion concentrations for tumor cell killing and lamellipodia‐induced cell metastasis, on‐demand release NO gas molecules for antibacterial therapy and neurotherapy, and perform tumor microenvironment‐responsive multimodal therapy, all achieved possible using tissue‐penetrating NIR light stimulation of low photon flux. In this work, recent progress on the construction and applications of UCNPs@MOFs heterostructures toward these regards is surveyed. An emphasis is placed on the classification of heterostructures (Janus, core@satellite, core@shell) with distinct geometric shapes as well as the fundamental upconversion FRET mechanism underpinning all their theranostic applications. Cutting‐edge applications on combined therapies, drug delivery, multimodal imaging, and biosensing are also highlighted, along with provided perspectives on the future development. [ABSTRACT FROM AUTHOR]

Chemo‐photodynamic therapy nanodelivery systems provide a potential strategy to enhance anticancer effect. However, the treatment efficiency of stimuli‐responsive nanotheranostics remains a challenge owing to off‐target properties, poor tissue penetration, and slow drugs release. Herein, di‐selenide‐bridged mesoporous silica (Se‐Se‐mSiO2) is introduced into a near‐infrared (NIR) light triggered and tumor microenvironment (TME)‐activated intelligent nanoplatform (UCNPs@mSiO2‐Ce6@Se‐Se‐mSiO2(DOX)@HA (UCSSDH)) realizing burst drug release on demand. Typically, the UCSSDH actively targets cancer cells and accumulates in tumor site through hyaluronic acid (HA). Then, under the irradiation of 980 nm NIR light, the upconverted 650 nm emission light activates photosensitizer Ce6 to produce the singlet oxygen (1O2) for photodynamic therapy (PDT). More importantly, 1O2 further cleaves di‐selenide bonds which are sensitive to reactive oxygen species (ROS), driving the rapid degradation of Se‐Se‐mSiO2 accompanied by the burst release of doxorubicin (DOX). Consequently, UCSSDH achieves efficient chemo‐photodynamic therapy of tumors. Last but not least, the upconversion nanoparticles (UCNPs) perform upconversion luminescence (UCL) imaging to monitor the drugs delivery. Collectively, an intelligent drug delivery system integrating therapeutic, monitoring, and targeting is exploited for NIR light‐triggered synergistic tumor therapy. This study broadens fresh vision into the development of controlled drug release and provides a momentous thought for potential clinical cancer therapy. [ABSTRACT FROM AUTHOR]

Upconversion Nanoparticles (UCNPs) have attracted exceptional attention due to their great potential in high-contrast, free-background biofluorescence deep tissue imaging and quantum sensing. Most of these interesting studies have been performed using an ensemble of UCNPs as fluorescent probes in bioapplications. Here, we report a synthesis of small and efficient YLiF4:Yb,Er UCNPs for single-particle imaging as well as sensitive optical temperature sensing. The reported particles demonstrated a bright and photostable upconversion emission at a single particle level under a low laser intensity excitation of 20 W/cm2. Furthermore, the synthesized UCNPs were tested and compared to the commonly used two-photon excitation QDs and organic dyes and showed a nine times better performance at a single particle level under the same experimental conditions. In addition, the synthesized UCNPs demonstrated sensitive optical temperature sensing at a single particle level within the biological temperature range. The good optical properties of single YLiF4:Yb,Er UCNPs open an avenue for small and efficient fluorescent markers in imaging and sensing applications. [ABSTRACT FROM AUTHOR]

Recently, nanoscale thermometry has attracted extensive attention. Here, we present an innovative approach to enhance the sensitivity of upconversion nanoparticles for thermometry through near-field manipulation. This method involves a composite structure consisting of photonic crystals and upconversion nanoparticles, with the near-field of the nanoparticles manipulated by tuning the absorption of the photonic crystals. The fluorescence intensity ratio (540nm/520 nm) of 4H 11/2 and4S 3/2 states of upconversion nanoparticles doped with Er3+ ions is sensitive to temperature change and employed as a temperature indicator that satisfies Boltzmann thermal equilibrium. The composite structure exhibited a relative thermometry sensitivity of 21.9 × 10−3 K−1 at 298 K, representing a significant improvement over pure core-shell upconversion nanoparticles with a 63.43% increase in relative sensitivity and a 675% increase in absolute sensitivity. This finding demonstrates the potential of our approach for advancing nanoscale thermometry. [ABSTRACT FROM AUTHOR]

Lanthanide-doped upconversion nanoparticles (UCNPs) absorb low-energy photons, in the near-infrared region (NIR), and emit high-energy photons, in the visible or ultraviolet region (UV/Vis). The higher energy radiation emissions can be used to promote plasmonic photocatalytic reactions by coupling UCNPs with plasmonic nanoparticles. Thus, in this work, highly crystalline β-NaYF4:Yb3+,Er3+@NaYF4:Nd3+@NaYF4 UCNPs capped with an amino-modified nanosized silica shell were coupled with Au nanospheres (13 ± 2 nm). The plasmonic-driven dimerization of 4-aminothiophenol (4-ATP) to 4,4′-dimercaptoazobenzene (DMAB) was carried out solely by using the UCNP visible emissions to excite the Au nanoparticle localized surface plasmon resonance band. The reaction was monitored in situ through surface-enhanced Raman spectroscopy (SERS) and optimal conditions were achieved in order to eliminate secondary influences during spectra acquisition. The SERS substrates containing either UCNPs@SiO2-NH2/Au or SiO2-NH2/Au nanoparticles were prepared by the drop-cast method in silicon substrates. In the studied reaction conditions, plasmonic photocatalytic activity was observed only in the substrates containing UCNPs and Au nanoparticles. The plasmonic-driven reaction was achieved by UCNPs excitation with a 980 nm laser (25.7 mW), aligned in a Raman spectrometer, only after 5 s of exposition. Interactive document mapping (IDMAP), which is an unsupervised pattern recognition method, was applied to analyze the numerous SERS spectra acquired during the plasmonic photocatalytic measurements. The high values found for the silhouette coefficient (0.88 for the Si_SiO2-NH2/Au and 0.76 for the Si_NYF@SiO2-NH/Au substrate) indicate that strong discrimination among the Raman spectra was achieved. Thus, through IDMAP, it was observed that the SERS spectra obtained for the substrates containing either UCNPs@SiO2-NH2/Au or SiO2-NH2/Au corresponded to spectral features, respectively, from the DMAB product and the 4-ATP reagent, evidencing that, in the optimized reaction conditions, the dimerization occurred only through the interaction of the UCNPs with the Au nanospheres. [ABSTRACT FROM AUTHOR]

We report a new strategy to fabricate a multifunctional composite photoanode containing TiO2 hollow spheres (TiO2‐HSs), Au nanoparticles (AuNPs) and novel NaYF4 : Yb,Er@NaLuF4 : Eu@SiO2 upconversion nanoparticles (UCNPs). The AuNPs are grown on the photoanode film including TiO2‐HSs and UCNPs by a simple in situ plasmonic treatment. As a result, an impressive power conversion efficiency of 14.13 % is obtained, which is a record for N719 dye‐based dye‐sensitized solar cells, demonstrating great potential for the solar cells toward commercialization. This obvious enhancement is ascribed to a collaborative mechanism of the TiO2‐HSs exhibiting excellent light‐scattering ability, of the UCNPs converting near‐infrared photons into visible photons and of the AuNPs presenting outstanding surface plasmon resonance effect. Notably, a steady‐state experiment further reveals that the champion cell exhibits 95.33 % retainment in efficiency even after 180 h of measurements, showing good device stability. [ABSTRACT FROM AUTHOR]

Abstract Background Photodynamic 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. Results In 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. Conclusion This therapeutic nanoplatform UCNPs@Ce6/3HBQ@CM, which combines PDT and CO therapy enables precise and efficient treatment of refractory glioblastoma.

Thromboembolism is the leading cause of cardiovascular mortality. Currently, for the lack of targeting, short half-life, low bioavailability and high bleeding risk of the classical thrombolytic drugs, pharmacological thrombolysis is usually a slow process based on micro-pumping. In addition, frequently monitoring and regulating coagulation functions are also required during (and after) the process of thrombolysis. To address these issues, a targeted thrombolytic and anticoagulation nanoplatform (UCATS-UK) is developed based on upconversion nanoparticles (UCNPs) that can convert 808 or 980 nm near-infrared (NIR) light into UV/blue light. This nanoplatform can target and enrich in the thrombus site. Synergistic thrombolysis and anticoagulation therapy thus could be realized through the controlled release of urokinase (UK) and nitric oxide (NO). Both in vitro and in vivo experiments have confirmed the excellent thrombolytic and anticoagulative capabilities of this multifunctional nanoplatform. Combined with the unique fluorescent imaging capability of UCNPs, this work is expected to contribute to the development of clinical thrombolysis therapy towards an integrated system of imaging, diagnosis and treatment.

UCNPs@AgBiS2 core-shell nanoparticles that AgBiS2 coated on the surface of upconversion nanoparticles (UCNPs) was successfully prepared through an ion exchange reaction. The photothermal conversion efficiency of AgBiS2 can be improved from 14.7% to 45% due to the cross relaxation between Nd ions and AgBiS2. The doping concentration of Nd ions played a critical role in the production of reactive oxygen species (ROS) and enhanced the photothermal conversion efficiency. The NaYF4:Yb/Er/Nd@NaYF4:Nd nanoparticles endows strong upconversion emissions when the doped concentration of Nd ions is 1% in the inner core, which excites the AgBiS2 shell to produce ROS for photodynamic therapy (PDT) of cancer cells. As a result, the as-prepared NaYF4:Yb/Er/Nd@NaYF4:Nd@AgBiS2 core-shell nanoparticles showed combined photothermal/photodynamic therapy (PTT/PDT) against malignant tumors. This work provides an alternative near-infrared light-active multimodal nanostructures for applications such as fighting against cancers.

Introduction. As the area of nano-based platforms for antimicrobial treatment aimed at pathogenic oral biofilms continues to expand, this review serves to bring together researchers from several disciplines to foster more collaboration and discovery among dental practitioners.

The incomplete detection of glioblastoma or the remnants of surgery constitute the primary reasons underlying glioblastoma recurrence. However, the current commercial MR Gd-based contrast agents (GBCAs) are not specialized, thus posing a potentially high risk of missed diagnosis or inaccurate boundary identification. MR contrast agents have been widely explored in conjugation with tumor-specific markers to preoperatively diagnose and identify the intraoperative positioning of glioblastoma. Herein, we developed a type of upconversion nanoparticle (UCNP), KMnF3:18%Yb, 2%Er, via the typical hydrothermal method, which possesses unique MR upconversion luminescence bimodal imaging. Furthermore, UCNPs were transformed to the aqueous phase by replacing oleic acid with amine–polyethylene glycol (PEG)–thiol (NH2–PEG–SH), further enabling the covalent conjugation of the glioblastoma metabolic ligand biotin. The as-prepared multifunctional biotin/PEG–UCNPs were characterized using various techniques. Moreover, their biocompatibility, especially with the brain, was systematically assessed via histological and hematological examinations. The results indicated negligible toxicity in vivo. As a proof of concept, biotin/PEG–UCNPs exhibited considerable potential for accurate definition of glioma infiltration boundaries for surgery as metabolic dual imaging contrast agents. [ABSTRACT FROM AUTHOR]

The dearth of technologies that allow gene modulation and therapy with high spatiotemporal precision remains a bottleneck in biomedical research and applications. Here we present a near‐infrared (NIR) light‐controlled nanosystem that allows spatiotemporally controlled regulation of gene expression and thus combinational tumor therapy. The nanosystem is built by engineering of an enzyme‐activatable antisense oligonucleotide and further combination with an upconversion nanoparticle‐based photodynamic system and a mitochondria localization signal. The system relies on photodynamic effect‐induced translocation of a DNA repair enzyme from nucleus into mitochondria, which enables spatially selective gene regulation via enzymatic reactions. We demonstrate that the NIR light‐induced mitochondrial photodamage and gene regulation enable enhanced antitumor effect. Our approach may enable the specific gene regulation and tumor treatment with high precision both spatially and temporally. [ABSTRACT FROM AUTHOR]

Constructing near‐infrared light (NIR) light‐enhanced room temperature gas sensors is becoming more promising for practical application. In this study, learning from the structure and photosynthetic process of chlorophyll thylakoid membranes in plants, the first "Thylakoid membrane" structural formaldehyde (HCHO) sensor is constructed by matching the upconversion emission of the lanthanide‐doped upconversion nanoparticles (UCNPs) and the UV–vis adsorption of the as‐prepared nanocomposites. The NIR‐mediated sensor exhibits excellent performances, including ultra‐high response (Ra / Rg = 2.22, 1 ppm), low practical limit of detection (50 ppb), reliable repeatability, high selectivity, and broadband spectral response. The practicality of the NIR‐mediated gas sensor is confirmed through the remote and external stimulation test. A study of sensing mechanism demonstrates that it is the UCNPs‐based light transducer produces more light‐induced oxygen species for gas response in the process of non‐radiative/radiative energy transfer, playing a key role in significantly improving the sensing properties of the sensor. The universality of NIR‐mediated gas sensors based on UCNPs is verified using ZnO, In2O3, and SnO2 systems. This work paves a way for fabricating high‐performance NIR‐mediated gas sensors and will expand the application fields of NIR light. [ABSTRACT FROM AUTHOR]

In order to improve the application of stem cell therapy, it is important to monitor the proliferation and differentiation of transplanted stem cells in real time, high sensitivity and high precision. Upconversion nanoparticles (UCNPs) have been employed as bioimaging agents and delivery vehicles for gene therapeutics in several types of cells. Herein, we fabricated multiple functional upconversion nanoparticles (FUC-NPs) as exogenous contrast agents to investigate the effect of FUC-NPs size on the efficiency of tracking human umbilical cord mesenchymal stem cells (HUCMSCs). We used TEM, DLS, MTT, etc. systematically detected the effects of nanoparticle dose and exposure time on HUCMSCs cytotoxicity. Our data showed that incubation of FUC-NPs, HUCMSCs are able to maintain their viability and differentiation ability. Interestingly, the small size FUC-NPs examined, S-FUCs, had a much higher uptake capability than the other FUC-NPs (B-FUCs, H-FUCs and R-FUCs).The study will aid in UCNPs for the engineering of stem cell application in the future. [ABSTRACT FROM AUTHOR]

Shigella, a typical and fatal foodborne pathogen with strong infectivity and survivability in foodstuff, demands a simple and sensitive detecting method. In this study, we reported a novel nanoplatform based on biofunctionalized magnetic nanoparticles (MNPs) modified upconversion nanoparticles (UCNPs) for rapid and specific determination of Shigella. Due to base pairing, Shigella aptamer-functionalized horseradish peroxidase (HRP) combined with complementary strand-modified MNPs@UCNPs. In the absence of Shigella, HRP associated with MNPs@UCNPs were magnetically separated, and colorless 3,3′,5,5′-tetramethylbenzidine (TMB) was oxidized into blue oxTMB. The overlap between oxTMB's absorption peak and MNPs@UCNPs' emission peak caused the fluorescence quenching at 545 nm. The MNPs@UCNPs fluorescence biosensor was achieved to detect Shigella in 1 h, with a limit of detection of 32 CFU/mL. This work showed a rapid and specific sensing platform and produced satisfactory chicken sample results. [ABSTRACT FROM AUTHOR]

Non-invasive visualization and monitoring of tissue-engineered structures in a living organism is a challenge. One possible solution to this problem is to use upconversion nanoparticles (UCNPs) as photoluminescent nanomarkers in scaffolds. We synthesized and studied scaffolds based on natural (collagen—COL and hyaluronic acid—HA) and synthetic (polylactic-co-glycolic acids—PLGA) polymers loaded with β-NaYF4:Yb3+, Er3+ nanocrystals (21 ± 6 nm). Histomorphological analysis of tissue response to subcutaneous implantation of the polymer scaffolds in BALB/c mice was performed. The inflammatory response of the surrounding tissues was found to be weak for scaffolds based on HA and PLGA and moderate for COL scaffolds. An epi-luminescent imaging system with 975 nm laser excitation was used for in vivo visualization and photoluminescent analysis of implanted scaffolds. We demonstrated that the UCNPs' photoluminescent signal monotonously decreased in all the examined scaffolds, indicating their gradual biodegradation followed by the release of photoluminescent nanoparticles into the surrounding tissues. In general, the data obtained from the photoluminescent analysis correlated satisfactorily with the histomorphological analysis. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a special form of phototherapy in which oxygen is needed, in addition to light and a drug called a photosensitiser (PS), to create cytotoxic species that can destroy cancer cells and various pathogens. PDT is often used in combination with other antitumor and antimicrobial therapies to sensitise cells to other agents, minimise the risk of resistance and improve overall outcomes. Furthermore, the aim of combining two photosensitising agents in PDT is to overcome the shortcomings of the monotherapeutic approach and the limitations of individual agents, as well as to achieve synergistic or additive effects, which allows the administration of PSs in lower concentrations, consequently reducing dark toxicity and preventing skin photosensitivity. The most common strategies in anticancer PDT use two PSs to combine the targeting of different organelles and cell-death mechanisms and, in addition to cancer cells, simultaneously target tumour vasculature and induce immune responses. The use of PDT with upconversion nanoparticles is a promising approach to the treatment of deep tissues and the goal of using two PSs is to improve drug loading and singlet oxygen production. In antimicrobial PDT, two PSs are often combined to generate various reactive oxygen species through both Type I and Type II processes. [ABSTRACT FROM AUTHOR]

Highly toxic reactive oxygen species (ROS) induced apoptosis and ferroptosis have been considered as significant cell death pathways for cancer therapy. However, insufficient amount of intracellular ROS extremely restricts the therapeutic effect. Toward this, we report a rationally designed nanocomposite (mUCC) with enhanced ROS generation ability, inducing the combination of apoptosis and ferroptosis through synergistic photodynamic therapy (PDT) and chemodynamic therapy (CDT). Under 808 nm near-infrared (NIR) light irradiation, photocatalytic reaction is triggered starting from the separation of electron-hole pairs on the surface of heterojunction (CeO2/CuO), realizing improved ROS production. Simultaneously, mUCC served as Fenton-like agent exhibits considerable ability to generate highly toxic ·OH under tumor microenvironment (TME). The boosted accumulation of ROS disrupts the redox balance within tumor cells and results in the integration of apoptosis and ferroptosis. In addition, mUCC shows satisfactory tumor targeting property benefiting from the cancer cell membrane functionalization under the guidance of magnetic resonance imaging (MRI) and NIR fluorescence imaging. The intelligent mUCC with good biocompatibility and excellent antitumor response achieves efficient tumor elimination under synergistic PDT and CDT. This work offers an elective approach for further development of ROS-based therapeutic nanoplatform in cancer therapy. [ABSTRACT FROM AUTHOR]

Fluorescence can be enhanced or quenched depending on the distance between the surface of a metal nanoparticle and the fluorophore molecule. Fluorescence enhancement by nearby metal particles is called metal-enhanced fluorescence (MEF). MEF shows promising potential in the field of fluorescence-based biological sensing. MEF-based biosensor systems generally fall into two platform categories: (1) a two/three-dimensional scaffold, or (2) a colloidal suspension. This review briefly summarizes the application studies using wavelength-dependent carbon dots (UV-VIS), noble metals (VIS), and upconversion nanoparticles (NIR to VIS), representative nanomaterials that contribute to the enhancement of fluorescence through the resonance energy transfer modulation and then presents a perspective on this topic. [ABSTRACT FROM AUTHOR]

Tobramycin (TOB) is a broad-spectrum aminoglycoside extensively used as veterinary medicine to treat bacterial infections. However, TOB residue in food and environment may cause great threat to human health. Here, we report, for the first time, the upconversion nanoparticles (UCNPs) for TOB detection based on Förster resonance energy transfer (FRET). The upconversion (UC) luminescence from core-shell structured UCNPs was effectively quenched after addition of MnO2 nanosheets due to the efficient energy transfer from the UCNPs to MnO2 nanosheets. When interacting with TOB, the UC luminescence was restored and increased as a result of coupling between TOB and aptamer, with MnO2 nanosheets dropping off the latter one. The UCNPs@SiO2-MnO2 aptasensors for TOB detection have a good selectivity and sensitivity in a linear range of 10–180 ng mL−1 with a limit of detection (LOD) of 3.04 ng mL−1. The sensors were tested for TOB detection in real samples of liquid milk and fishes and the results are very good and satisfactory. These type of aptasensors are promising for practical applications as they have a high sensitivity, selectivity, low LOD, and are autofluorescence-free.

Upconversion nanoparticle (UCNP)-driven polymerization attracts great attention due to the ability of near-infrared light to penetrate deeper into biological media and synthetic materials than ultraviolet or visible light. Despite significant progress, the limitation of near-infrared light-triggered polymerization is associated with a key element of the photocurable composition, a UCNP/photoinitiator complex or a nanoinitiator. To determine the impact of resonance energy transfer from UCNPs to photoinitiator (PI) and its effect on polymerization, we developed two different photocurable compositions consisting of the polyethylene glycol diacrylate (PEG-DA), ultraviolet- and blue-emitting NaYF4: Yb3+, Tm3+ UCNPs with hydrophobic surface combined with water-soluble or insoluble PI. We found that transfer energy in these nanoinitiators proceeds differently: in UCNP/water-soluble PI (lithium phenyl-2,4,6-trimethylbenzoylphosphinate or LAP), it occurs through the photon-mediated transfer while in UCNP/water-insoluble PI (2-benzyl-2-(dimethylamino)-4′-morpholinobutyrophenone or Irgacure 369), it takes place via the non-radiative resonant energy transfer. The impact of these processes in homolytic decomposition of initiator is extremely important in terms of the precisely controlled fabrication of polymer structures. PEG-DA facilitates the affinity between hydrophilic and hydrophobic components of the photocurable composition, which provides UCNP-driven cross-linking of biopolymers such as methacrylated hyaluronic acid and gelatin. 3D structures were prototyped to demonstrate the one-step rapid procedure of nanoinitiator preparation and emphasize the control of the energy transfer in UCNP/PI complexes for further development of UCNP-driven polymerization.

Electrospun nanofibers possess a large surface area and a three-dimensional porous network that makes them a perfect material for embedding functional nanoparticles for diverse applications. Herein, we report the trends in embedding upconversion nanoparticles (UCNPs) in polymeric nanofibers for making an advanced miniaturized (bio)analytical device. UCNPs have the benefits of several optical properties, like near-infrared excitation, anti-Stokes emission over a wide range from UV to NIR, narrow emission bands, an extended lifespan, and photostability. The luminescence of UCNPs can be regulated using different lanthanide elements and can be used for sensing and tracking physical processes in biological systems. We foresee that a UCNP-based nanofiber sensing platform will open opportunities in developing cost-effective, miniaturized, portable and user-friendly point-of-care sensing device for monitoring (bio)analytical processes. Major challenges in developing microfluidic (bio)analytical systems based on UCNPs@nanofibers have been reviewed and presented.

In this work, we report a new concept of upconversion-powered photoelectrochemical (PEC) bioanalysis. The proof-of-concept involves a PEC bionanosystem comprising a NaYF4:Yb,Tm@NaYF4 upconversion nanoparticles (UCNPs) reporter, which is confined by DNA hybridization on a CdS quantum dots (QDs)/indium tin oxide (ITO) photoelectrode. The CdS QD-modified ITO electrode was powered by upconversion absorption together with energy transfer effect through UCNPs for a stable photocurrent generation. By measuring the photocurrent change, the target DNA could be detected in a specific and sensitive way with a wide linear range from 10 pM to 1 μM and a low detection limit of 0.1 pM. This work exploited the use of UCNPs as signal reporters and realized upconversion-powered PEC bioanalysis. Given the diversity of UCNPs, we believe it will offer a new perspective for the development of advanced upconversion-powered PEC bioanalysis.

Vibrio parahaemolyticus is a halophilic and heat-labile gram-negative bacterium and is the most prevalent foodborne bacterium in seafood. In order to develop a rapid and sensitive method for detecting the foodborne pathogenic bacterium Vibrio parahaemolyticus, an aptamer-modified magnetic nanoparticle and an aptamer-modified upconversion nanoparticle were synthesised and used as a capture probe and a signal probe, respectively. The aptamer-modified magnetic nanoparticle, V. parahaemolyticus cell, and aptamer-modified upconversion nanoparticle formed a sandwich-like complex, which was rapidly separated from a complex matrix using a magnetic force, and the bacterial concentration was determined by fluorescence intensity analysis. The results showed that the fluorescence intensity signal correlated positively with the concentration of V. parahaemolyticus in the range of 3.2 × 102 to 3.2 × 105 CFU/mL, with a linear equation of y = 296.40x − 217.67 and a correlation coefficient of R2 = 0.9610. The detection limit of the developed method was 4.4 CFU/mL. There was no cross-reactivity with other tested foodborne pathogens. This method is highly specific and sensitive for the detection of V. parahaemolyticus, and can achieve the qualitative detection of this bacterium in a complex matrix.

Novel and high-security anti-counterfeiting technology has always been the focus of attention and research. This work proposes a nanocomposite combination of upconversion nanoparticles (UCNPs) and perovskite quantum dots (PeQDs) to achieve color-adjustable dual-mode luminescence anti-counterfeiting. Firstly, a series of NaGdF4: Yb/Tm UCNPs with different sizes were synthesized, and their thermal-enhanced upconversion luminescence performances were investigated. The upconversion luminescence (UCL) intensity of the samples increases with rising temperature, and the UCL thermal enhancement factor rises as the particle size decreases. This intriguing thermal enhancement phenomenon can be attributed to the mitigation of surface luminescence quenching. Furthermore, CsPbBr3 PeQDs were well adhered to the surfaces and surroundings of the UCNPs. Leveraging energy transfer and the contrasting temperature responses of UCNPs and PeQDs, this nanocomposite was utilized as a dual-mode thermochromic anti-counterfeiting system. As the temperature increases, the color of the composite changes from green to pink under 980 nm excitation, while it displays green to non-luminescence under 365 nm excitation. This new anti-counterfeiting material, with its high security and convenience, has great potential in anti-counterfeiting applications.

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 (SC50) and detection range (SC10 to SC90) 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.

Food safety has become a topic of global concern in the recent decades. The significant food safety incidents occur from time to time around the world, seriously threatening the public health and causing extensive economic losses. In particular, the occurrence of COVID-19 highlights the importance of the food safety for the public health. Therefore, there is an urgent need to establish a fast, simple, sensitive, and efficient method for the detection of food safety. In recent years, the upconversion (UC) nanotechnology has been widely used in the field of food detection. The UC fluorescence analysis technology possesses the advantages of ultra-sensitivity detection, non-invasiveness, light stability, etc., and has broad application prospects in the field of food safety. After cladding and surface modification, it can be combined with other substances through a variety of mechanisms, such as electrostatic interaction, thereby expanding its application in the food safety detection. Thus, overall, there is a vital need to evaluate and utilize the potential of UC nanoparticles in the field of rapid detection of food safety.

Introduction: Dexamethasone (DEX), as an important enduring-effect glucocorticoid (GC), holds great promise in the field of lung ischemia-reperfusion injury (LIRI) comprehensive therapy owing to its immunomodulatory properties, such as inducing apoptosis and cell cycle distribution. However, its potent anti-inflammatory application is still restricted because of multiple internal physiologic barriers.Methods: Herein, we developed upconversion nanoparticles (UCNPs) coated with photosensitizer/capping agent/fluorescent probe-modified mesoporous silica (UCNPs@mSiO2[DEX]-Py/β-CD/FITC, USDPFs) for precise DEX release synergistic LIRI comprehensive therapy. The UCNPs were designed by covering an inert YOF:Yb shell on the YOF:Yb, Tm core to achieve high-intensity blue and red upconversion emission upon Near-Infrared (NIR) laser irradiation.Results: Under suitable compatibility conditions, the molecular structure of photosensitizer can be damaged along with capping agent shedding, which endowed USDPFs with an outstanding capability to carry out DEX release controlling and fluorescent indicator targeting. Furthermore, the hybrid encapsulating of DEX significantly increased utilization of nano-drugs, improving the water solubility and bioavailability, which was conducive to developing the anti-inflammatory performance of USDPFs in the complex clinical environment.Discussion: The response-controlled release of DEX in the intrapulmonary microenvironment can reduce normal cell damage, which can effectively avoid the side effects of nano-drugs in anti-inflammatory application. Meanwhile, the multi-wavelength of UCNPs endowed nano-drugs with the fluorescence emission imaging capacity in an intrapulmonary microenvironment, providing precise guidance for LIRI.

Accurate blood glucose determination is essential to the clinical diagnosis and management of diabetes. This work establishes an inner filter effect (IFE) strategy between upconversion nanoparticles (UCNPs) and quinone-imine complex for glucose monitoring in human serum simply and efficiently. In this system, the enzyme glucose oxidase (GOx) catalyzes the reaction of glucose into hydrogen peroxide (H2O2) and gluconic acid when compulsion by oxygen. In the presence of horseradish peroxidase (HRP), the produced H2O2 can catalytically oxidize phenol and 4-amino antipyrine (4-AAP) to generate quinone-imine products. The purple-colored quinone-imine complex effectively absorbed the fluorescence of NaYF4:Yb3+, Er3+ UCNPs, leading to the strong fluorescence quenching of UCNPs through IFE. Thus, a new approach was established for glucose monitoring by determining the fluorescence intensity. Under the optimal condition, this approach shows better linearity to glucose from 2–240 μmol/L with a low detection limit at 1.0 μmol/L. Owing to the excellent fluorescence property and background-free interference of the UCNPs, the biosensor was applied for glucose measurements in human serum and got a satisfactory result. Furthermore, this sensitive and selective biosensor revealed great potential for the quantitative analysis of blood glucose or different kinds of H2O2-involved biomolecules for the application of clinical diagnosis.

Abstract Amyloid‐β (Aβ) and Tau proteins are the main components of Aβ plaques and neurofibrillary tangles in Alzheimer's disease (AD), and their abnormal aggregation is closely related to the pathogenesis of AD. The production of reactive oxygen species (ROS) and the aggregation of Aβ and Tau form a vicious circle, which leads to the aggravation of AD. However, inhibiting the aggregation of Aβ and Tau or scavenging ROS is not able to effectively reverse the progression of AD. Herein, we prepared a H2O2 responsive multifunctional nanocomposite UCNPs@mSiO2‐MB@AuNPs (abbreviated as USMA) to inhibit the aggregation of Aβ and Tau. In this system, USMA could respond to H2O2 to detach gold nanoparticles (AuNPs) and lead to the release of methylene blue (MB) from mesoporous silica (mSiO2), where AuNPs and MB can inhibit Aβ and Tau aggregation, respectively. Furthermore, USMA could consume H2O2 by reacting with them. Meanwhile, upconversion luminescence of UCNPs can be used to track USMA and monitor MB release, which could provide information on the content of MB in the lesion area. Importantly, the USMA can effectively reduce the cytotoxicity induced by Aβ and Tau aggregation. This work opens up a possibility to improve therapeutic efficacy for the treatment of AD.

Overuse of antibiotics such as enrofloxacin (ENR) can lead to their residues in environment and food and ultimately endanger human health. It's essential to build a rapid, sensitive and selective biosensor to detect the antibiotics residues. Herein, an autofluorescence free near-infrared (NIR) laser excited functionalized upconversion nanoparticles (UCNPs) based turn-on aptasensor for ENR detection is presented. Efficient Fӧrster resonance energy transfer (FRET) from aptamer modified core-shell UCNPs with highly enhanced upconversion (UC) luminescence to MnO2 nanosheets occurs. Based on the UC luminescence recovery of the UCNPs-MnO2 aptasensor caused by ENR, this luminescence turn-on UCNPs-MnO2 aptasensor shows highly sensitive and selective detection of ENR in linear range of 0.5–3000 ng mL−1 with a limit of detection (LOD) at 0.0642 ng mL−1 in diluted commercially available milk solution without pretreatment. The proposed aptasensor demonstrates high sensitivity, excellent selectivity, no background autofluorescence for high signal-to-noise ratio and low LOD for the fast detection of antibiotics residue, holding great potential for environmental and food safety detection of antibiotics.

Background: Photodynamic 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. Results: In 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. Conclusion: This therapeutic nanoplatform UCNPs@Ce6/3HBQ@CM, which combines PDT and CO therapy enables precise and efficient treatment of refractory glioblastoma. [ABSTRACT FROM AUTHOR]

Genetically engineered bacteria have aroused attention as micro-nano drug delivery systems in situ. However, conventional designs of engineered bacteria usually function constantly or autonomously, which might be non-specific or imprecise. Therefore, designing and optimizing in situ control strategy are important methodological progress for therapeutic researches of intestinal engineered bacteria. Here, a micro-nano optogenetic system based on probiotic was developed combining microelectronics, nanotechnology, and synthetic biology to achieve in situ controllable drug delivery. Firstly, optogenetic engineered Lactococcus lactis was orally administrated in the intestinal tract. A wearable optical device was designed to control optical signals remotely. Then, L. lactis could be customized to secrete peptides according to optical signals. As an example, optogenetic L. lactis system can be constructed to secrete glucagon-like peptide-1 (GLP-1) under the control of the wearable optical device to regulate metabolism. To improve the half-life of GLP-1 in vivo, Fc-domain fused GLP-1 was optimally used. Using this strategy, blood glucose, weight, and other features were well controlled in rats and mice models. Furthermore, upconversion microcapsules were introduced to increase the excitation wavelength of the optogenetic system for better penetrability. This strategy has biomedical potential to expand the toolbox for intestinal engineered bacteria. [ABSTRACT FROM AUTHOR]