Upconversion Nanoparticles Research Articles

Construction of core-triple shell upconversion nanostructures NaNdF4:Yb,Gd@NaGdF4:Yb@NaGdF4:Yb,Er@NaGdF4 with high FRET efficiency for the biochemical sensor

Upconversion nanoparticles (UCNPs) are excellent energy donors for Föster resonance energy transfer (FRET) systems. However, the lower FRET efficiency to some extend limits its application. To improve the efficiency of FRET, NaNdF4:Yb,Gd@NaGdF4:Yb@NaGdF4:Yb,Er@NaGdF4 core-triple shell (CTS) UCNPs with sensitizers in the core region and activators doped in the outer shell region were successfully prepared by changing the traditional core-shell structure design sequence. By introducing a certain amount of Gd3+ into the core nanoparticles, the crystal growth process of core nanoparticles was regulated, solving the problem of excessive and uneven size caused by high concentration of sensitizers. The insertion of Yb3+ doped transition layer weakens the negative effect between Nd3+ and activator ions, and enhances the luminescence intensity. In addition, comparing CTS UCNPs with UCNPs prepared in the traditional core-shell structure design sequence proves that CTS UCNPs have higher FRET efficiency. A biochemical sensing system was designed using this novel core-shell structure UCNPs, achieving simultaneous detection of GSH and Cd2+ with detection limits of 4.2 nM and 15.2 nM, respectively. The new core-shell structure UCNPs have broader application prospects in the field of biochemical sensing design.

Upconversion-based chiral nanoprobe for highly selective dual-mode sensing and bioimaging of hydrogen sulfide in vitro and in vivo

Chiral assemblies have become one of the most active research areas due to their versatility, playing an increasingly important role in bio-detection, imaging and therapy. In this work, chiral UCNPs/CuxOS@ZIF nanoprobes are prepared by encapsulating upconversion nanoparticles (UCNPs) and CuxOS nanoparticles (NPs) into zeolitic imidazolate framework-8 (ZIF-8). The novel excited-state energy distribution-modulated upconversion nanostructure (NaYbF4@NaYF4: Yb, Er) is selected as the fluorescence source and energy donor for highly efficient fluorescence resonance energy transfer (FRET). CuxOS NP is employed as chiral source and energy acceptor to quench upconversion luminescence (UCL) and provide circular dichroism (CD) signal. Utilizing the natural adsorption and sorting advantages of ZIF-8, the designed nanoprobe can isolate the influence of other common disruptors, thus achieve ultra-sensitive and highly selective UCL/CD dual-mode quantification of H2S in aqueous solution and in living cells. Notably, the nanoprobe is also capable of in vivo intra-tumoral H2S tracking. Our work highlights the multifunctional properties of chiral nanocomposites in sensing and opens a new vision and idea for the preparation and application of chiral nanomaterials in biomedical and biological analysis.

Near-Infrared Light-Mediated Antibacterial Photodynamic Therapy Based on Erythrosine-Functionalized Mesoporous Silica-Coated Upconversion Nanoplatform.

Infectious diseases caused by bacteria pose a serious threat to public health, and more worryingly, the unregulated application of antibiotics accelerates the emergence of bacterial resistance, presenting a major challenge to the effective treatment of infectious diseases caused by bacteria. Therefore, there is an urgent necessity to develop efficient and safe antimicrobial systems. Photodynamic therapy (PDT) is an attractive therapeutic approach that does not induce bacterial resistance. However, the clinical application of PDT has been limited by several factors, including the lower tissue penetration depth of photoactivation under visible light irradiation and the uncertain biosafety of photosensitizers (PS). This work presents an near infrared (NIR)-triggered core-shell upconversion nanoparticle-based PDT system composed of mesoporous silica-coated lanthanide-doped upconversion nanoparticles loaded with the photosensitizer erythrosine (UCSE). Upon NIR-triggering, erythrosine generates highly efficient reactive oxygen species that disrupt the cell membranes of Staphylococcus aureus and Escherichia coli, exhibiting a potent photodynamic antimicrobial effect. It is worth noting that the UCSE also exhibits excellent biosafety. In conclusion, we present an efficient NIR-triggered nanoantimicrobial system with excellent antimicrobial capacity and biosafety, which is a new therapeutic strategy for the control of bacterial infectious diseases.

Fluorescent-colorimetric dual signal ratio sensor with AuNRs@UCNPs superstructure nanoprobe for accurate hypochlorite detection

There is a significant need for sensitive and selective hypochlorite (ClO-) detection in rheumatoid arthritis, especially at the site of inflammation. However, the traditional single signal strategy based on visible emission cannot meet sensitive and accurate analysis requirements in practical applications. In this work, a novel fluorescent-colorimetric dual-signal ratio luminescent nanoprobe (superstructure AuNRs@UCNPs) was developed based on Förster resonance energy transfer (FRET) between the ClO- responsive gold nanorods (AuNRs) and lanthanide doped up-conversion nanoparticles (UCNPs). ClO- gradually etched AuNRs to produce corresponding color changes and plasmon resonance absorption peak shifts. The luminescence at 650 nm of UCNPs gradually recovered, while the luminescence at 540 nm gradually weakened. It allows for the sensitive and accurate detection of ClO- with excellent limits of detection (0.156 μM for the fluorescent ratio method and 0.231 μM for the colorimetric method). It provides a powerful dual guarantee for ClO- detection. The detection in serum of actual samples shows that the probe has reasonable accuracy and precision.

NIR Light and GSH Dual-Responsive Upconversion Nanoparticles Loaded with Multifunctional Platinum(IV) Prodrug and RGD Peptide for Precise Cancer Therapy.

Platinum(II) drugs as a first-line anticancer reagent are limited by side effects and drug resistance. Stimuli-responsive nanosystems hold promise for precise spatiotemporal manipulation of drug delivery, with the aim to promote bioavailability and minimize side effects. Herein, a multitargeting octahedral platinum(IV) prodrug with octadecyl aliphatic chain and histone deacetylase inhibitor (phenylbutyric acid, PHB) at axial positions to improve the therapeutic effect of cisplatin was loaded on the upconversion nanoparticles (UCNPs) through hydrophobic interaction. Followed attachment of DSPE-PEG2000 and arginine-glycine-aspartic (RGD) peptide endowed the nanovehicles with high biocompatibility and tumor specificity. The fabricated nanoparticles (UCNP/Pt(IV)-RGD) can be triggered by upconversion luminescence (UCL) irradiation and glutathione (GSH) reduction to controllably release Pt(II) species and PHB, inducing profound cytotoxicity. Both in vitro and in vivo experiments demonstrated that UCNP/Pt(IV)-RGD exhibited remarkable antitumor efficiency, high tumor-targeting specificity, and real-time UCL imaging capacity, presenting an intelligent platinum(IV) prodrug-loaded nanovehicle for UCL-guided dual-stimuli-responsive combination therapy.

Enhanced photocatalytic degradation of polylactide (PLA) through TiO2-based up-conversion nanoparticles

As a degradable polymer material, the regulation of the degradation rate of polylactide (PLA) under an actual light exposure environment is of significant importance for realizing its multifaceted applications. This study aims to enhance the photodegradation of PLA under irradiation with lower-energy wavelengths by using TiO2-based up-conversion nanoparticles (UCNPs). Two modification methods were employed: doping TiO2 with Yb3+/Er3+/Tm3+ ions integrated within the TiO2 lattice, and creating a composite photocatalyst by adhering Y2O3: Yb3+/Er3+/Tm3+ to the exterior of TiO2 grains. The study investigated the impact of these two different TiO2-based UCNPs on the photocatalytic degradation rate and mechanism of PLA under simulated sunlight irradiation. Research has found that the doped TiO2, due to its narrower bandgap and higher photon utilization efficiency during the up-conversion process, exhibited superior catalytic efficiency in catalyzing the photodegradation reactions of PLA compared to unmodified TiO2 and composite TiO2. This work proposes a novel strategy for preparing PLA composites with enhanced photodegradation speed provided by modified TiO2, efficient light energy utilization offered by the up-conversion process, and potential applications in more advanced packaging and agricultural fields.

A smart capecitabine imprinted nanocontainer with the dual-responsive performance to pH/NIR light

Capecitabine (CAP) is a kind of prodrug that can be metabolized into 5-fluorouracil (5-FU) in vivo, so it is usually classified as the antimetabolite fluoropyrimidine deoxynucleoside analog. In this paper, CAP, upconversion nanoparticles (UCNPs), 3,5-dicarboxy-4-methacrylate-based azobenzene (MAPDIA)/acrylic acid-functionalized gelatin, N,N′-methylene bisacrylamide (MBA), and ammonium persulfate (APS) were used as template, light trigger, bifunctional monomers, cross-linking agent and initiator, respectively. By using the free-radical polymerization and the molecular imprinting technique, the potential drug delivery nanocontainer CAP-MIP with the dual-responsive performance to pH/near infrared light (NIR) was successfully prepared. Furthermore, the characterization of CAP-MIP was also carried out by the modern instrumental analysis such as FTIR, XRD, TGA, BET and so on. The stimulus-responsive release experiment in vitro indicated the maximum cumulative release rate of CAP changed from 1.71 % to 89.54 % when the pH value in medium varied from 1.2 to 8.3, and the equilibrium release time point also greatly prolonged to 420 min from 40 min, respectively. When irradiated by 980 nm monochromatic NIR light in the same solution of pH 6.8, the maximum release rate of the sample could reach 96.21 % at 180 min, which respectively corresponded to the data of 41.84 % at 420 min under the condition of the absence of additional NIR light. In addition, CAP-MIP also had the excellent specific adsorption for CAP with the selectivity factor of 2.904 and the maximum CAP-loaded capacity of 7 mg•g−1. The above information denoted the target material should be of some potential in drug delivery system application.

Upconversion luminescence resonance energy transfer (LRET)-based dual-channel biosensor for rapid detection of coronavirus

Researchers recently have been working on a sensitive, accurate, and easily accessible way to detect coronaviruses. Traditional polymerase chain reaction detection technology has high sensitivity and specificity, but there are some problems, such as a complicated detection process, false negatives caused by gene mutation of coronavirus, and easy infection of operators. Antigen detection, which does not require gene amplification and other preprocessing, can be operated by non-medical staff for rapid detection. However, its detection sensitivity requires high reliability and further improvement. Accordingly, a biosensor based on luminescent resonance energy transfer (LRET) from upconversion nanoparticles (UCNPs) to gold nanoparticles (AuNPs) and antigen detection has been developed for rapid and sensitive detection of N protein of SARS-CoV-2. By adjusting the reaction conditions, LRET can be realized by making the spectral overlap between the luminescence of UCNPs and the absorption band of AuNPs, which can effectively avoid the generation of biological background light and the interference of other signals in the test process. In addition, the thiol-ene click reaction was used to link Thiol-PEG-COOH to UCNPs to improve its biocompatibility. The antigen recognition of the coronavirus based on the as-proposed detection method can be further realized on the test paper. A linear response is obtained ranging from 10 ng mL−1 to 1280 ng mL−1, and the detection limit is around 0.80 ng mL−1 with a detection time of around 10 minutes, which has a wide range of potential future. This fast and sensitive biosensor for coronavirus detection can be further reflected in the test paper and is promising for practical applications.

Optical super-resolution nanothermometry via stimulated emission depletion imaging of upconverting nanoparticles.

From engineering improved device performance to unraveling the breakdown of classical heat transfer laws, far-field optical temperature mapping with nanoscale spatial resolution would benefit diverse areas. However, these attributes are traditionally in opposition because conventional far-field optical temperature mapping techniques are inherently diffraction limited. Optical super-resolution imaging techniques revolutionized biological imaging, but such approaches have yet to be applied to thermometry. Here, we demonstrate a super-resolution nanothermometry technique based on highly doped upconverting nanoparticles (UCNPs) that enable stimulated emission depletion (STED) super-resolution imaging. We identify a ratiometric thermometry signal and maintain imaging resolution better than ~120 nm for the relevant spectral bands. We also form self-assembled UCNP monolayers and multilayers and implement a detection scheme with scan times >0.25 μm2/min. We further show that STED nanothermometry reveals a temperature gradient across a joule-heated microstructure that is undetectable with diffraction limited thermometry, indicating the potential of this technique to uncover local temperature variation in wide-ranging practical applications.

Upconverting Ultra-Thin Bi2O2CO3 Nanosheets for Synergistic Photodynamic Therapy and Radiotherapy.

Synergistic therapy has become the major therapeutic method for malignant tumors in clinical. Photodynamic therapy (PDT) and radiotherapy (RT) always combine together because of their identical anti-tumor mechanisms, that is reactive oxygen species are generated by the use of radiosensitizers after irradiation by X-ray to efficiently kill cancer cells, PDT also follows similar mechanism. Full exposure of energy-absorbing species in nanomaterials to X-ray or near-infrared light irradiation makes the energy interchange between nanomaterials and surrounding H2O or dissolved oxygen easier, however, it remains challenging. Herein, an ultrathin two-dimensional (2D) nanosheet (NS) is developed, Bi2O2CO3, doped with lanthanide ions to give out upconversion luminescence, where the high Z elements Bi, Yb, and Er promote the radio-sensitizing effect. To the surprise, lanthanide activator ions gave out completely different luminescence properties compared with traditional upconversion nanoparticles. Less dopant of Er ions in nanosheets lattice resulted in brighter red emission, which provides more efficient PDT. Under RT/PDT combined treatment, NS shows a good tumor growth-inhibiting effect. In addition, synergistic therapy requires lower radiation dose than conventional radiotherapy and lower light power than single photodynamic therapy, thus greatly reducing radiation damage caused by RT and thermal damage caused by PDT.

Modulated upconversion luminescence of water-dispersed NaErF4@NaYF4 nanoparticles by introducing Tm3+/Ho3+ as energy capture centers under multi-wavelength NIR excitation

Water-dispersed red upconversion nanoparticles (UCNPs) have great application prospects in the biomedical field. Thus, a series of Er3+-based upconversion nanoparticles (Er-UCNPs) with excellent red upconversion luminescence under three-wavelength NIR excitation (808/980/1550 nm) were prepared by a simple thermal decomposition method, and then further functionalized by PAA to achieve good water dispersibility. Compared with NaErF4 bare core, the emission intensity of Er-UCNPs samples doping of 0.5%Tm3+ and 0.5%Ho3+ as energy capture centers was significantly enhanced, and further improved after coating with NaYF4 inert shell. Meanwhile, among all Er-UCNPs@NaYF4 samples, NaErF4@NaYF4 exhibited the highest emission intensity and longest luminescence lifetime due to the efficient suppression of luminescence quenching effect, while NaErF4:0.5%Tm3+@NaYF4 showed highest red luminescence purity owing to the energy transfer process between Tm3+(3H5) and Er3+(4I13/2). The hydrophilic Er-UCNPs@NaYF4@PAA samples still maintained good red luminescence under multi-wavelength excitation. The luminescence enhancement mechanism in Er-UCNPs@NaYF4 was discussed in detail based on spectral characteristics. The as-prepared water-dispersed Er-UCNPs@NaYF4@PAA with bright red luminescence under multi-wavelength NIR excitation will have potential applications in targeted therapy and deep tissue imaging.

NIR-Remote Selectively Triggered Buprenorphine Hydrochloride Release from Microneedle Patches for the Treatment of Neuropathic Pain.

Neuropathic pain is a prevalent form of intermittent chronic pain, affecting approximately 7-10% of the global population. However, the current clinical administration methods, such as injection and oral administration, are mostly one-time administration, which cannot achieve accurate control of pain degree and drug dose. Herein, we developed near-infrared (NIR) light-responsive microneedle patches (MNPs) to spatiotemporally control the drug dose released to treat neuropathic pain according to the onset state. The mechanism of action utilizes upconversion nanoparticles to convert NIR light into visible and ultraviolet light. This conversion triggers the rapid rotation of the azobenzene molecular motor in the mesoporous material, enabling the on-demand controlled release of a drug dose. Additionally, MNs are used to overcome the barrier of the stratum corneum in a minimally invasive and painless manner, effectively promoting the transdermal penetration of drug molecules. The effectiveness of these patches has been demonstrated through significant results. Upon exposure to NIR light for five consecutive cycles, with each cycle lasting 30 s, the patches achieved a precise release of 318 μg of medication. In a mouse model, maximum pain relief was observed within 1 h of one cycle of NIR light exposure, with the effects lasting up to 6 h. The same level of precise treatment efficacy was maintained for subsequent pain episodes with similar light exposure. The NIR-controlled drugs precision-released MNPs provide a novel paradigm for the treatment of intermittent neuropathic pain.

Upconverting Nanoparticle-based Enhanced Luminescence Lateral-Flow Assay for Urinary Biomarker Monitoring.

Development of efficient portable sensors for accurately detecting biomarkers is crucial for early disease diagnosis, yet remains a significant challenge. To address this need, we introduce the enhanced luminescence lateral-flow assay, which leverages highly luminescent upconverting nanoparticles (UCNPs) alongside a portable reader and a smartphone app. The sensor's efficiency and versatility were shown for kidney health monitoring as a proof of concept. We engineered Er3+- and Tm3+-doped UCNPs coated with multiple layers, including an undoped inert matrix shell, a mesoporous silica shell, and an outer layer of gold (UCNP@mSiO2@Au). These coatings synergistically enhance emission by over 40-fold and facilitate biomolecule conjugation, rendering UCNP@mSiO2@Au easy to use and suitable for a broad range of bioapplications. Employing these optimized nanoparticles in lateral-flow assays, we successfully detected two acute kidney injury-related biomarkers─kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL)─in urine samples. Using our sensor platform, KIM-1 and NGAL can be accurately detected and quantified within the range of 0.1 to 20 ng/mL, boasting impressively low limits of detection at 0.28 and 0.23 ng/mL, respectively. Validating our approach, we analyzed clinical urine samples, achieving biomarker concentrations that closely correlated with results obtained via ELISA. Importantly, our system enables biomarker quantification in less than 15 min, underscoring the performance of our novel UCNP-based approach and its potential as reliable, rapid, and user-friendly diagnostics.

Tailoring upconversion fluorescence of lanthanide doped nanocrystals by coupling to single microcavity mode with specific symmetry.

Lanthanide-doped upconversion nanoparticles have unique optical properties that can absorb low-energy infrared photons and then emit higher-energy visible ones, which have been widely used for advanced optical sensors and fluorescent probes. Efficiently tailoring the upconversion emission is desirable for meeting the wavelength requirement in various application fields. However, up to now, optimizing the composition combining with core/shell structure is still the predominant way to reach this goal. Here, we show that the relative intensities of the emission peaks of upconverting nanoparticles can be tuned by coupling to single microcavity mode with specific symmetry. Theoretical calculation based on the finite-difference time-domain (FDTD) indicates that the symmetries of the microcavity modes dominate their resonant absorption properties in the visible region. As a result, the upconversion emission peaks vary in these microcavities with different symmetries. This route can be developed for tailoring the emission spectra of other luminescent materials, such as quantum dots and fluorescent dyes.

Near-Infrared Light-Activatable DNA Tentacles for Efficient Inhibition of Tumor Metastasis by Bio-Orthogonal Cell Assembly.

Tumor metastasis remains a major challenge in cancer management. Among various treatment strategies, immune cell-based cancer therapy holds a great potential for inhibiting metastasis. However, its wide application in cancer therapy is restricted by complex preparations, as well as inadequate homing and controllability. Herein, we present a groundbreaking approach for bioorthogonally manipulating tumor-NK (natural killer) cell assembly to inhibit tumor metastasis. Multiple dibenzocyclootyne (DBCO) groups decorated long single-stranded DNA were tail-modified on core-shell upconversion nanoparticles (CSUCNPs) and condensed by photosensitive chemical linker (PC-Linker) DNA to shield most of the DBCO groups. On the one hand, the light-triggered DNA scaffolds formed a cross-linked network by click chemistry, effectively impeding tumor cell migration. On the other hand, the efficient cellular assembly facilitated the effective communication between tumor cells and NK-92 cells, leading to enhanced immune response against tumors and further suppression of tumor metastasis. These features make our strategy highly applicable to a wide range of metastatic cancers.

A novel MNPs@GO biosensor- integrated upconversion fluorescence cuvette for simultaneous detection of Salmonella typhimurium and Staphylococcus aureus

An upconversion fluorescence biosensor was developed and employed in a self-designed cuvette engineered for the detection of Salmonella typhimurium and Staphylococcus aureus in chicken samples. The cuvette consisted of a hollow cylinder filled with alendronic acid-modified upconversion nanoparticles (ADA@UCNPs) and solid quartz cube blocks and could provide a stable and reusable fluorescent donor. In addition, the fluorescence inner filter mechanism (IEF) between two fluorescence quenchers (3,3′,5,5′-tetramethylbenzidine oxide (oxTMB) and 5-bromo-4-chloro-3-indolyl phosphate/nitroblue tetrazole (oxBCIP/NBT)) and ADA@UCNPs in the cuvette could be triggered. After sample injection, bacteria-targeting aptamers labeled with horseradish peroxidase (HRP) or alkaline phosphatase (AP) fell off the magnetic graphene oxide (MNPs@GO), resulting in the blockage of the enzymatic reaction. This led to an increase in the yellow-green upconversion fluorescence peaks at 547 nm and 658 nm. The whole detection process could be accomplished within 40 min and required the minimum amounts of ADA@UCNPs and MNPs@GO. The limit of detection was as low as 14 CFU/mL for Salmonella typhimurium and 33 CFU/mL for Staphylococcus aureus. To sum up, the upconversion fluorescence biosensor holds a potential in rapid analysis and detection of foodborne pathogenic bacteria.

Interplay between a Heptamethine Cyanine Dye Sensitizer (IR806) and Lanthanide Upconversion Nanoparticles

AbstractLanthanide‐doped upconversion nanoparticles (UCNPs) have attractive emission properties but suffer from weak light‐absorbing capacities and thereby relatively low brightnesses. This motivates using strongly absorbing dye molecules as antennas and sensitizers. However, despite much effort, understanding of this dye‐UCNP interplay is still limited. Major sensitization mechanisms are still under discussion, largely because there is a lack of effective means to observe key factors such as dark state transitions within the dyes. Here, a combined spectroscopic procedure is established to systematically investigate the photophysics behind the dye‐UCNP interaction, embracing fluorescence‐based transient‐state excitation‐modulation, lifetime and correlation spectroscopy, and spectrofluorometry/spectrophotometry. With this procedure the heptamethine cyanine dye IR806, a typical UCNP sensitizer is studied, its photophysical model is established, its photophysics in UCL‐sensitization‐related environments is deciphered, and the energy transfer from the IR806 singlet excited state to Yb3+ (UCNP sensitizer ion) can be identified as the dominant sensitization mechanism. These studies suggest that IR806 can form non‐emissive H‐aggregates at the nanoparticle surfaces, which can be dissociated after certain light excitation duration (typically>100 µs). Moreover, buildup of a non‐fluorescent, photo‐redox state of IR806 after longer irradiation times (10–100 ms) can deleteriously affect its UCL sensitization effect, inferring an optimal excitation duration for dye‐sensitized UCNPs, relevant for, e.g., optical imaging applications.

Controllable chemical synthesis of core-shell NaGdF4:Yb3+/Er3+@Bi4O5I2/Bi5O7I Z-scheme heterojunction for efficient tetracycline hydrochloride photodegradation

Constructing heterojunction photocatalysts that can make additional utilization of near-infrared (NIR) light has been a global scientific problem and has gained widespread research interest. Upconversion nanoparticles (UCNPs) collaborate with semiconductors to construct UCNPs-based photocatalysts that are used to improve solar energy utilization. In this work, the as-prepared UCNPs-based photocatalysts consisting of NaGdF4:Yb3+/Er3+ (NGFYE) and bismuth oxyiodide (BOI) are synthesized by chemical epitaxial growth method and in-situ calcination process. The crystalline phase, morphology, optical and electrochemical properties of NGFYE@BOI samples are investigated in detail. Besides, Bi4O5I2/Bi5O7I Z-type heterojunction is confirmed by EPR test. Moreover, the photocatalytic elimination of tetracycline hydrochloride (TCH) and its photocatalytic mechanism by NGFYE@BOI samples are explored. This work may provide a promising idea for the efficient and controlled synthesis of UCNPs-based photocatalysts, which will contribute to the future utilization of solar energy.

Zinc oxide nanoparticles with catalase-like nanozyme activity and near-infrared light response: A combination of effective photodynamic therapy, autophagy, ferroptosis, and antitumor immunity

We prepared biocompatible and environment-friendly zinc oxide nanoparticles (ZnO NPs) with upconversion properties and catalase-like nanozyme activity. Photodynamic therapy (PDT) application is severely limited by the poor penetration of UV–Visible light and a hypoxic tumor environment. Here, we used ZnO NPs as a carrier for the photosensitizer chlorin e6 (Ce6) to construct zinc oxide–chlorin e6 nanoparticles (ZnO-Ce6 NPs), simultaneously addressing both problems. In terms of penetration, ZnO NPs convert 808 nm near-infrared light into 401 nm visible light to excite Ce6, achieving deep-penetrating photodynamic therapy under long-wavelength light. Interestingly, the ability to emit short-wavelength light under long-wavelength light is usually observed in upconversion nanoparticles. As nanozymes, ZnO NPs can catalyze the decomposition of hydrogen peroxide in tumors, providing oxygen for photodynamic action and relieving hypoxia. The enhanced photodynamic action produces a large amount of reactive oxygen species, which overactivate autophagy and trigger immunogenic cell death (ICD), leading to antitumor immunotherapy. In addition, even in the absence of light, ZnO and ZnO-Ce6 NPs can induce ferroptosis of tumor cells and exert antitumor effects.

Cellular Uptake of Upconversion Nanoparticles Based on Surface Polymer Coatings and Protein Corona.

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