Cancer-Thylakoid Hybrid Membrane Camouflaged Thulium Oxide Nanoparticles with Oxygen Self-Supply Capability for Tumor-Homing Phototherapy.

Nanomaterials that generate reactive oxygen species (ROS) upon light irradiation have significant applications in various fields, including photodynamic therapy (PDT) that is widely recognized as a highly momentous strategy for the eradication of cancer cells. However, the ROS production rate of photosensitizers, as well as the tumor hypoxia environment, are two major challenges that restrict the widespread application of PDT. In this study, a cancer-thylakoid hybrid membrane-camouflaged thulium oxide nanoparticles (Tm2O3) for tumor-homing phototherapy through dual-stage-light-guided ROS generation and oxygen self-supply is developed. Tm2O3 as a type II photosensitizer are viable for NIR-stimulated ROS generation due to the unique energy levels, large absorption cross section, and long lifetime of the 3H4 state of Tm ions. The thylakoid membrane (TK) plays a catalase-like role in converting hydrogen peroxide into oxygen and also acts as a natural photosensitizer that can generate lethal ROS through electron transfer when exposed to light. In addition, fluorescence dye DiR is embedded in the hybrid membrane for in vivo tracing as well as photothermal therapy. Results show that tumors in Tm2O3@TK-M/DiR group are effectively ablated following dual-stage-light irradiation, highlighting the promising potential of rare-earth element-based type II photosensitizers in various applications.

Comparative Analyses and Ablation Efficiency of Thulium Fiber Laser by Stone Composition.

PURPOSE: There are limited data on ablation effects of thulium fiber laser (TFL) settings with varying stone composition. Similarly, little is known surrounding the photothermal effects of TFL lithotripsy regarding the chemical and structural changes after visible char formation. We aim to understand the TFL's ablative efficiency across various stone types and laser settings, while simultaneously investigating the photothermal effects of TFL lithotripsy. MATERIALS AND METHODS: Human specimens of calcium oxalate monohydrate, calcium oxalate dihydrate, uric acid, struvite, cystine, carbonate apatite, and brushite stones were ablated using 13 prespecified settings with the Coloplast TFL Drive. Pre- and postablation mass, ablation time, and total energy were recorded. Qualitative ablative observations were recorded at 1-minute intervals with photographs and gross description. Samples were analyzed with Fourier-transform infrared spectroscopy pre- and postablation and electron microscopy postablation to assess the photothermal effects of TFL. RESULTS: Across all settings and stone types, 0.05 J × 1000 Hz was the best numerically efficient ablation setting. When selected for more clinically relevant laser settings (ie, 10-20 W), 0.2 J × 100 Hz, short pulse was the most numerically efficient setting for calcium oxalate dihydrate, cystine, and struvite stones. Calcium oxalate monohydrate ablated with the best numerical efficiency at 0.4 J × 40 Hz, short pulse. Uric acid and carbonate apatite stones ablated with the best numerical efficiency at 0.3 J × 60 Hz, short pulse. Brushite stones ablated with the best numerical efficiency at 0.5 J × 30 Hz, short pulse. Pulse duration impacted ablation effectiveness greatly with 6/8 (75%) of inadequate ablations occurring in medium or long pulse settings. The average percent of mass lost during ablation was 57%; cystine stones averaged the highest percent mass lost at 71%. Charring was observed in 36/91 (40%) specimens. Charring was most often seen in uric acid, cystine, and brushite stones across all laser settings. Electron microscopy of char demonstrated a porous melting effect different to that of brittle fracture. Fourier-transform infrared spectroscopy of brushite char demonstrated a chemical composition change to amorphous calcium phosphate. CONCLUSIONS: We describe the optimal ablation settings based on stone composition, which may guide urologists towards more stone-specific care when using thulium laser for treating renal stones (lower energy settings would be safer for ureteral stones). For patients with unknown stone composition, lasers can be preset to target common stone types or adjusted based on visual cues. We recommend using short pulse for all TFL lithotripsy of calculi and altering the settings based on visual cues and efficiency to minimize the charring, an effect which can make the stone refractory to further dusting and fragmentation.

Near-Infrared Light-Excited Reactive Oxygen Species Generation by Thulium Oxide Nanoparticles.

Exploring materials that can absorb near-infrared (NIR) light to produce reactive oxygen species (ROS) is necessary for many fields. Herein we show that thulium oxide nanoparticles are viable for NIR-stimulated ROS generation. This property may be related to the unique energy levels, large absorption cross section, low fluorescence emission, and ∼10-3 s lifetime of the 3H4 state of Tm ions. We further demonstrate the impact of these nanoparticles on photodynamic therapy (PDT), in which impressive tumor inhibition was recorded after exposure to either a broadband halogen lamp or an 808 nm laser. Our results may provide insight into the areas of photocatalysis, pollution treatment, and fine chemical synthesis.

Upconversion-nanoparticle-functionalized Janus micromotors for efficient detection of uric acid.

We report enzyme-powered upconversion-nanoparticle-functionalized Janus micromotors, which are prepared by immobilizing uricase asymmetrically onto the surface of silicon particles, to actively and rapidly detect uric acid. The asymmetric distribution of uricase on silicon particles allows the Janus micromotors to display efficient motion in urine under the propulsion of biocatalytic decomposition of uric acid and simultaneously detect uric acid based on the luminescence quenching effect of the UCNPs modified on the other side of SiO2. The efficient motion of the motors greatly enhances the interaction between UCNPs and the quenching substrate and improves the uric acid detection efficiency. Overall, such a platform using uric acid simultaneously as the detected substrate and motion fuel offers considerable promise for developing multifunctional micro/nanomotors for a variety of bioassay and biomedical applications.

Photonic Crystal Effects on Upconversion Enhancement of LiErF4:0.5%Tm3+@LiYF4 for Noncontact Cholesterol Detection.

Cholesterol is a vital compound in maintenance for human health, and its concentration levels are tightly associated with various diseases. Therefore, accurate monitoring of cholesterol is of great significance in clinical diagnosis. Herein, we fabricated a noncontact biosensor based on photonic crystal-enhanced upconversion nanoparticles (UCNPs) for highly sensitive and interference-free cholesterol detection. By compounding LiErF4:0.5%Tm3+@LiYF4 UCNPs with poly(methyl methacrylate) (PMMA) photonic crystals (OPCs), we were able to selectively tune the coupling of the photonic band gap to the excitation field and modulate the upconversion (UC) luminescence intensity, given the unique multi-wavelength excitation property of LiErF4:0.5%Tm3+@LiYF4. A 48.5-fold enhancement of the monochromatic red UC emission was ultimately achieved at 980 nm excitation, ensuring improved detection sensitivity. Based on the principle of quenching of the intense monochromic red UC emission by the oxidation products of 3,3',5,5'-tetramethylbenzidine (TMB) yielded from the cholesterol cascade reactions, the biosensor has a detection limit of 1.6 µM for cholesterol with excellent specificity and stability. In addition, the testing results of the as-designed biosensor in patients are highly consistent with clinical diagnostic data, providing a sensitive, reliable, reusable, interference-free, and alternative strategy for clinical cholesterol detection.

A CORM loaded nanoplatform for single NIR light-activated bioimaging, gas therapy, and photothermal therapy in vitro.

Carbon monoxide (CO) can cause mitochondrial dysfunction, inducing apoptosis of cancer cells, which sheds light on a potential alternative for cancer treatment. However, the existing CO-based compounds are inherently limited by their chemical nature, such as high biological toxicity and uncontrolled CO release. Therefore, a nanoplatform - UmPF - that addresses such pain points is urgently in demand. In this study, we have proposed a nanoplatform irradiated by near-infrared (NIR) light to release CO. Iron pentacarbonyl (Fe(CO)5) was loaded in the mesoporous polydopamine layer that was coated on rare-earth upconverting nanoparticles (UCNPs). The absorption wavelength of Fe(CO)5 overlaps with the emission bands of the UCNPs in the UV-visible light range, and therefore the emissions from the UCNPs can be used to incite Fe(CO)5 to control the release of CO. Besides, the catechol groups, which are abundant in the polydopamine structure, serve as an ideal locating spot to chelate with Fe(CO)5; in the meantime, the mesoporous structure of the polydopamine layer improves the loading efficiency of Fe(CO)5 and reduces its biological toxicity. The photothermal effect (PTT) of the polydopamine layer is highly controllable by adjusting the external laser intensity, irradiation time and the thickness of the polydopamine layer. The results illustrate that the combination of CO gas therapy (GT) and polydopamine PTT brought by the final nanoplatform can be synergistic in killing cancer cells in vitro. More importantly, the possible toxic side effects can be effectively prevented from affecting the organism, since CO will not be released in this system without near-infrared light radiation.

Mapping Drug-Induced Neuropathy through In-Situ Motor Protein Tracking and Machine Learning.

Chemotherapy can induce toxicity in the central and peripheral nervous systems and result in chronic adverse reactions that impede continuous treatment and reduce patient quality of life. There is a current lack of research to predict, identify, and offset drug-induced neurotoxicity. Rapid and accurate assessment of potential neuropathy is crucial for cost-effective diagnosis and treatment. Here we report dynamic near-infrared upconversion imaging that allows intraneuronal transport to be traced in real time with millisecond resolution, but without photobleaching or blinking. Drug-induced neurotoxicity can be screened prior to phenotyping, on the basis of subtle abnormalities of kinetic characteristics in intraneuronal transport. Moreover, we demonstrate that combining the upconverting nanoplatform with machine learning offers a powerful tool for mapping chemotherapy-induced peripheral neuropathy and assessing drug-induced neurotoxicity.

Synthesis and in vitro preliminary evaluation of prostate-specific membrane antigen targeted upconversion nanoparticles as a first step towards radio/fluorescence-guided surgery of prostate cancer.

Over the last decade, upconversion nanoparticles (UCNP) have been widely investigated in nanomedicine due to their high potential as imaging agents in the near-infrared (NIR) optical window of biological tissues. Here, we successfully develop active targeted UCNP as potential probes for dual NIR-NIR fluorescence and radioactive-guided surgery of prostate-specific membrane antigen (PSMA)(+) prostate cancers. We designed a one-pot thermolysis synthesis method to obtain oleic acid-coated spherical NaYF4:Yb,Tm@NaYF4 core/shell UCNP with narrow particle size distribution (30.0 ± 0.1 nm, as estimated by SAXS analysis) and efficient upconversion luminescence. Polyethylene glycol (PEG) ligands bearing different anchoring groups (phosphate, bis- and tetra-phosphonate-based) were synthesized and used to hydrophilize the UCNP. DLS studies led to the selection of a tetra-phosphonate PEG(2000) ligand affording water-dispersible UCNP with sustained colloidal stability in several aqueous media. PSMA-targeting ligands (i.e., glutamate-urea-lysine derivatives called KuEs) and fluorescent or radiolabelled prosthetic groups were grafted onto the UCNP surface by strain-promoted azide-alkyne cycloaddition (SPAAC). These UCNP, coated with 10 or 100% surface density of KuE ligands, did not induce cytotoxicity over 24 h incubation in LNCaP-Luc or PC3-Luc prostate cancer cell lines or in human fibroblasts for any of the concentrations evaluated. Competitive binding assays and flow cytometry demonstrated the excellent affinity of UCNP@KuE for PSMA-positive LNCaP-Luc cells compared with non-targeted UCNP@CO2H. Furthermore, the binding of UCNP@KuE to prostate tumour cells was positively correlated with the surface density of PSMA-targeting ligands and maintained after 125I-radiolabelling. Finally, a preliminary biodistribution study in LNCaP-Luc-bearing mice demonstrated the radiochemical stability of non-targeted [125I]UCNP paving the way for future in vivo assessments.

Six-photon upconverted excitation energy lock-in for ultraviolet-C enhancement.

Photon upconversion of near-infrared (NIR) irradiation into ultraviolet-C (UVC) emission offers many exciting opportunities for drug release in deep tissues, photodynamic therapy, solid-state lasing, energy storage, and photocatalysis. However, NIR-to-UVC upconversion remains a daunting challenge due to low quantum efficiency. Here, we report an unusual six-photon upconversion process in Gd3+/Tm3+-codoped nanoparticles following a heterogeneous core-multishell architecture. This design efficiently suppresses energy consumption induced by interior energy traps, maximizes cascade sensitizations of the NIR excitation, and promotes upconverted UVC emission from high-lying excited states. We realized the intense six-photon-upconverted UV emissions at 253 nm under 808 nm excitation. This work provides insight into mechanistic understanding of the upconversion process within the heterogeneous architecture, while offering exciting opportunities for developing nanoscale UVC emitters that can be remotely controlled through deep tissues upon NIR illumination.

Laser-induced breakdown spectroscopy as a readout method for immunocytochemistry with upconversion nanoparticles.

Immunohistochemistry (IHC) and immunocytochemistry (ICC) are widely used to identify cancerous cells within tissues and cell cultures. Even though the optical microscopy evaluation is considered the gold standard, the limited range of useful labels and narrow multiplexing capabilities create an imminent need for alternative readout techniques. Laser-induced breakdown spectroscopy (LIBS) enables large-scale multi-elemental analysis of the surface of biological samples, e.g., thin section or cell pellet. It is, therefore, a potential alternative for IHC and ICC readout of various labels or tags (Tag-LIBS approach). Here, we introduce Tag-LIBS as a method for the specific determination of HER2 biomarker. The cell pellets were labeled with streptavidin-conjugated upconversion nanoparticles (UCNP) through a primary anti-HER2 antibody and a biotinylated secondary antibody. The LIBS scanning enabled detecting the characteristic elemental signature of yttrium as a principal constituent of UCNP, thus indirectly providing a reliable way to differentiate between HER2-positive BT-474 cells and HER2-negative MDA-MB-231 cells. The comparison of results with upconversion optical microscopy and luminescence intensity scanning confirmed that LIBS is a promising alternative for the IHC and ICC readout.

The ROS-generating photosensitizer-free NaYF4:Yb,Tm@SiO2upconverting nanoparticles for photodynamic therapy application.

In this work we adapt rare-earth-ion-doped NaYF4nanoparticles coated with a silicon oxide shell (NaYF4:20%Yb,0.2%Tm@SiO2) for biological and medical applications (for example, imaging of cancer cells and therapy at the nano level). The wide upconversion emission range under 980 nm excitation allows one to use the nanoparticles for cancer cell (4T1) photodynamic therapy (PDT) without a photosensitizer. The reactive oxygen species (ROS) are generated by Tm/Yb ion upconversion emission (blue and UV light). Thein vitroPDT was tested on 4T1 cells incubated with NaYF4:20%Yb,0.2%Tm@SiO2nanoparticles and irradiated with NIR light. After 24 h, cell viability decreased to below 10%, demonstrating very good treatment efficiency. High modification susceptibility of the SiO2shell allows for attachment of biological molecules (specific antibodies). In this work we attached the anti-human IgG antibody to silane-PEG-NHS-modified NaYF4:20%Yb,0.2%Tm@SiO2nanoparticles and a specifically marked membrane model by bio-conjugation. Thus, it was possible to perform a selective search (a high-quality optical method with a very low-level organic background) and eventually damage the targeted cancer cells. The study focuses on therapeutic properties of NaYF4:20%Yb,0.2%Tm@SiO2nanoparticles and demonstrates, upon biological functionalization, their potential for targeted therapy.

Synthesis, RL and OSL characterization of thulium doped NaMgF3 neighborite.

The aim of this work is to study the dosimetric properties of tissue-equivalent thulium doped NaMgF3 neighborites and to determine their possible application as dosimeters in personal dosimetry. In this aspect, radioluminescence (RL) and optically stimulated luminescence (OSL) dosimetric properties of undoped and Tm3+ -doped NaMgF3 have been investigated for the first time. Samples were synthesized by solid state reaction and by considering a stoichiometric mixture of pure NaF and MgF2 reagents. Two emission peaks centered at 460 and 360 nm have been found in the RL emission spectrum of the doped samples, which can be ascribed to the 1D2 - 3F4 and 1D2 - 3H6 transitions of Tm3+ cations, respectively. Maximum OSL emission under blue light stimulation has been found for samples doped with 0.2 mol % of thulium. Furthermore, the OSL signal of this compound depends linearly on dose within the range 0.05-100 Gy. Besides, its OSL signal features satisfactory repeatability and a minimum detectable dose of 0.04 Gy. Finally, it has been found a low fading of the OSL signal of approximately 13% after the first 60 h, after which the OSL response remains constant. The obtained results suggest the feasibility of using this compound as an OSL detector in personal dosimetry.

Application of NaYF4:Yb/Er/Tm UCNPs in Array-Based Sensing of Neurotransmitters: From a Single Particle to a Multichannel Sensor Array.

A novel multichannel sensor array has been designed using a single, yet multiemissive lanthanide-doped upconversion nanoparticle (UCNP). The energy levels of lanthanide ions gave rise to several emission bands which were exploited as individual sensor elements for the recognition of four important neurotransmitters (NTs): dopamine, norepinephrine, levodopa, and serotonin. At alkaline conditions, the oxidation products of these NTs quenched the fluorescence emissions of UCNPs with different quenching degrees. The resulting fingerprint multichannel emission profiles from NaYF4:Yb/Er/Tm UCNPs allowed the discrimination of NTs with excellent accuracy. The recognition was further verified in artificial cerebrospinal fluid, as a complex biological media. We believe that the designed UCNP-based multichannel sensor array offers innovative insights into the discrimination of various chemical signatures using a single measurement.

UCNP-based Photoluminescent Nanomedicines for Targeted Imaging and Theranostics of Cancer.

Theranostic approach is currently among the fastest growing trends in cancer treatment. It implies the creation of multifunctional agents for simultaneous precise diagnosis and targeted impact on tumor cells. A new type of theranostic complexes was created based on NaYF4: Yb,Tm upconversion nanoparticles coated with polyethylene glycol and functionalized with the HER2-specific recombinant targeted toxin DARPin-LoPE. The obtained agents bind to HER2-overexpressing human breast adenocarcinoma cells and demonstrate selective cytotoxicity against this type of cancer cells. Using fluorescent human breast adenocarcinoma xenograft models, the possibility of intravital visualization of the UCNP-based complexes biodistribution and accumulation in tumor was demonstrated.

Controllable synthesis of rare earth (Gd3+,Tm3+) doped Prussian blue for multimode imaging guided synergistic treatment.

Gd3+ and Tm3+ doped Prussian blue (Gd/Tm-PB) with high uniformity and dispersibility was synthesized by a facile solvothermal method. The conditions for the synthesis of Gd/Tm-PB were explored. Through the regulation of the ratio of Gd3+/Tm3+, the Gd/Tm-PB particles with the optimal size (about 150-200 nm) and the best fluorescence and photothermal effect were obtained. On the basis of the optimal Gd/Tm-PB, further coated by polydopamine (PDA) functionalized metal-organic frameworks (MOFs), a multifunctional platform Gd/Tm-PB@ZIF-8/PDA for cancer diagnosis and treatment was established. Doxorubicin (DOX) was selected as a drug model and the drug loading of Gd/Tm-PB@ZIF-8/PDA was found to be 81 mg g-1. Cytotoxicity analysis indicated that Gd/Tm-PB@ZIF-8/PDA was highly biocompatible. The DOX release at different pH values and GSH concentrations revealed an excellent pH/GSH-triggered drug release. Through the combination of the near infrared photothermal performance of Gd/Tm-PB, chemo-photothermal therapy can be achieved to further improve the anti-cancer efficiency. In addition, the Gd/Tm-PB@ZIF-8/PDA nanoparticles can be tracked by fluorescence imaging (FOI) and magnetic resonance imaging (MRI). Cell FOI and in vivo MRI experiments showed the potential application of Gd/Tm-PB@ZIF-8/PDA in dual mode imaging guided therapy. In vivo antitumor experiments demonstrated the higher anticancer efficacy of Gd/Tm-PB@ZIF-8/PDA with a combined effect of chemo-photothermal therapy. This work provides a new strategy for nano-drug carriers in the direction of integrated diagnosis and treatment.

Intracellular photoswitchable neuropharmacology driven by luminescence from upconverting nanoparticles.

Photoswitchable drugs are small-molecule optical probes that undergo chromatically selective control of drug efficacy using, most often, UV-visible light. Here we report that luminescence produced by near-infrared stimulation of NaYF4:TmYb nanoparticles can be used for "remote control" of an azobenzene-based photochromic ion channel blocker of neurons in living brain slices.

Thulium oxide nanoparticles as radioenhancers for the treatment of metastatic cutaneous squamous cell carcinoma.

Metastases from cutaneous squamous cell carcinoma (cSCC) occur in 2%-5% of cases. Surgery is the standard treatment, often combined with adjuvant radiotherapy. Concurrent carboplatin treatment with post-operative radiotherapy may be prescribed, although it has not shown benefit in recent clinical trials in high-risk cSCC patients. The novel high-Z nanoparticle thulium (III) oxide has been shown to enhance radiation dose delivery to brain tumors by specific uptake of these nanoparticles into the cancerous tissue. As the dose-enhancement capacity of thulium oxide nanoparticles following radiotherapy against metastatic cSCC cells is unknown, its efficacy as a radiosensitizer was evaluated, with and without carboplatin. Novel and validated human patient-derived cell lines of metastatic cSCC were used. The sensitivity of the cells to radiation was investigated using short-term proliferation assays as well as clonogenic survival as the radiobiological endpoint. Briefly, cells were irradiated with 125 kVp orthovoltage x-rays (0-6 Gy) with and without thulium oxide nanoparticles (99.9% trace metals basis; 50 µg ml-1) or low dose carboplatin pre-sensitization. Cellular uptake of the nanoparticles was first confirmed by microscopy and found to have no impact on short-term cell survival for the cSCC cells, highlighting the biocompatibility of thulium oxide nanoparticles. Clonogenic cell survival assays confirmed radio-sensitization when exposed to thulium nanoparticles, with the cell sensitivity increasing by a factor of 1.24 (calculated at the 10% survival fraction) for the irradiated cSCC cells. The combination of carboplatin with thulium oxide nanoparticles with irradiation did not result in significant further reductions in survival compared to nanoparticles alone. This is the first study to provide in vitro data demonstrating the independent radiosensitization effect of high-Z nanoparticles against metastatic cSCC with or without carboplatin. Further preclinical investigations with radiotherapy plus high-Z nanoparticles for the management of metastatic cSCC are warranted.

Effect of ytterbium amount on LaNbO4:Tm3+,Yb3+ nanoparticles for bio-labelling applications.

PURPOSE: This work investigates how Yb3+ concentration affects the luminescent properties of LaNbO4 nanoparticles for medical imaging applications. Due to the highly transparent optical window for organic tissues in the near infrared region (650-1000 nm), upconversion fluorescence allows near infrared wavelengths to penetrate deeply into tissues, which is useful in biomedical areas such as biodetection, activated phototherapy, and screening. MATERIALS/METHOD: Upconversion nanoparticles based on LaNbO4 doped with Tm3+ and Yb3+ were prepared by the one-step industrial process called Spray Pyrolysis. Samples with different Tm3+:Yb3+ molar ratios (1:4, 1:8 and 1:16) were obtained. RESULTS: The X-ray powder diffractograms of all the samples displayed the typical peaks of a crystalline material (tetragonal phase). Emission bands emerged in the blue, red, and near infrared regions, and they corresponded to the Tm3+1G4 → 3H6 (475 nm), 1G4 → 3F4 (650 nm), 3F2,3 â†’ 3H6 (690 nm), and 3H4 → 3H6 (803 nm) transitions, which indicated a two-photon absorption process. As for bio-labelling application, the results indicated that Yb3+ concentration was directly related to signal intensity. CONCLUSIONS: The intensity of positive conversion emissions depends directly on Yb3+ concentration. The bio-labelling tests pointed to the potential application of these materials. The sample containing the highest amount of Yb3+ provided better results and was easier to detect than the standard sample.

Multifunctional Complexes Based on Photoluminescent Upconversion Nanoparticles for Theranostics of the HER2-Positive Tumors.

Combining diagnostic and therapeutic functions in one agent is a promising strategy in the development of personalized approaches to the treatment of cancer. The opportunity to combine diagnostics and therapy appeared with the development of nanobiotechnologies and was realized in the concept of theranostics. To date, a number of promising agents based on nanomaterials capable of diagnosing, targeted therapeutic effects, and monitoring the response of tumor cells were obtained within the approach of theranostics. In this work, a new type of theranostic complexes based on upconversion nanoparticles coated with polyethylene glycol and functionalized with the DARPin-LoPE recombinant targeted toxin was developed. Selective binding of complexes to human breast adenocarcinoma cells overexpressing the HER2 receptor and specific toxicity to them were shown.

Selective Decoating-Induced Activation of Supramolecularly Coated Toxic Nanoparticles for Multiple Applications.

In spite of the rapid emergence of numerous nanoparticles (NPs) for biomedical applications, it is often challenging to precisely control, or effectively tame, the bioactivity/toxicity of NPs, thereby exhibiting limited applications in biomedical areas. Herein, we report the construction of hyaluronic acid (HA)-laminated, otherwise toxic methylviologen (MV), NPs via ternary host-guest complexation among cucurbit[8]uril, trans-azobenzene-conjugated HA, and MV-functionalized polylactic acid NPs (MV-NPs). The high, nonspecific toxicity of MV-NPs was effectively shielded (turned off) by HA lamination, as demonstrated in cells, zebrafish, and mouse models. The supramolecular host-guest interaction-mediated HA coating offered several HA-MV-NP modalities, including hyaluronidase locally and photoirradiation remotely, to precisely remove HA lamination on demand, thereby endowing materials with the capability of selective decoating-induced activation (DIA) for applications as a user-friendly herbicide, a selective antibacterial agent, or an anticancer nanomedicine. This work offers facile supramolecular coating and DIA strategies to effectively tame and precisely control the bioactivity and toxicity of functional nanomaterials for diverse applications.