CeO2 and Glucose Oxidase Co-Enriched Ti3C2Tx MXene for Hyperthermia-Augmented Nanocatalytic Cancer Therapy.

Foreseen as foundational in forthcoming oncology interventions are multimodal therapeutic systems. Nevertheless, the tumor microenvironment (TME), marked by heightened glucose levels, hypoxia, and scant concentrations of endogenous hydrogen peroxide could potentially impair their effectiveness. In this research, two-dimensional (2D) Ti3C2 MXene nanosheets are engineered with CeO2 nanozymes and glucose oxidase (GOD), optimizing them for TME, specifically targeting cancer therapy. Following our therapeutic design, CeO2 nanozymes, embodying both peroxidase-like and catalase-like characteristics, enable transformation of H2O2 into hydroxyl radicals for catalytic therapy while also producing oxygen to mitigate hypoxia. Concurrently, GOD metabolizes glucose, thereby augmenting H2O2 levels and disrupting the intracellular energy supply. When subjected to a near-infrared laser, 2D Ti3C2 MXene accomplishes photothermal therapy (PTT) and photodynamic therapy (PDT), additionally amplifying cascade catalytic treatment via thermal enhancement. Empirical evidence demonstrates robust tumor suppression both in vitro and in vivo by the CeO2/Ti3C2-PEG-GOD nanocomposite. Consequently, this integrated approach, which combines PTT/PDT and enzymatic catalysis, could offer a valuable blueprint for the development of advanced oncology therapies.

Switchable up-conversion luminescence bioimaging and targeted photothermal ablation in one core-shell-structured nanohybrid by alternating near-infrared light.

In photothermal therapy (PTT), simultaneous achievement of imaging and hyperthermia mediated by a single laser inevitably risks damaging normal tissues before treatment. Herein, a core-shell-structured GdOF:Yb/Er@(GNRs@BSA) nanohybrid was designed and fabricated by conjugating gold nanorods (GNRs) on the surfaces of GdOF:Yb/Er nanoparticles by a facile procedure. By alternating near-infrared (NIR) light appropriately, high photothermal efficiency for PTT and good up-conversion luminescence (UCL) imaging can be achieved in this structure, which can substantially solve the heat-induced risk during the theranostic process. Furthermore, good biocompatibility and phagocytosis can be realized by modifying bovine serum albumin (BSA) on the surface of the GNRs, and the conjugation of folic acid (FA) endows this nanohybrid with targeting function. It is noted that the size of the GNRs prepared by the one-pot method is much smaller than that by the seed-mediated method, which is not only conducive to uniform heat distribution during intratumoral therapy, but also contributes to the nanohybrid metabolic decomposition and fluorescence tracing after treatment. Moreover, this product can also be utilized as a good magnetic resonance imaging (MRI) and computed tomography (CT) contrast agent, which can provide versatile imaging properties in the field of cancer clinical treatment.

Polypyrrole-coated UCNPs@mSiO2@ZnO nanocomposite for combined photodynamic and photothermal therapy.

Designing multifunctional nanoplatforms for the purpose of simultaneous theranostic modalities is critical to address the challenges of cancer therapy. Also, single modalities of phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT), cannot meet the requirements of highly efficient treatment. Here, a core-shell-shell nanostructure consisting of a core of upconversion nanoparticles (UCNPs), a layer of mesoporous silica with anchored ZnO nanodots, and an outer layer of polypyrrole (PPy) was developed. In the proposed construct, the emitted ultraviolet (UV) light from the UCNPs core upon 980 nm near-infrared light irradiation can trigger the ZnO nanodots to activate ambient O2 molecules around cancerous tissues to produce toxic reactive oxygen species (ROS), realizing the PDT function. On the other hand, the coated PPy layer can concurrently give rise to an obvious heat effect upon NIR light illumination, thus achieving synergistic PDT and PTT effects; this results in excellent anti-tumor efficiency in vitro and in vivo. Furthermore, in hand with the upconversion luminescence (UCL) and computed tomography (CT) imaging derived from the UCNPs core, dual-mode imaging directed cancer therapy has been realized.

Enhanced up/down-conversion luminescence and heat: Simultaneously achieving in one single core-shell structure for multimodal imaging guided therapy.

Upon near-infrared (NIR) light irradiation, the Nd(3+) doping derived down-conversion luminescence (DCL) in NIR region and thermal effect are extremely fascinating in bio-imaging and photothermal therapy (PTT) fields. However, the concentration quenching induced opposite changing trend of the two properties makes it difficult to get desired DCL and thermal effect together in one single particle. In this study, we firstly designed a unique NaGdF4:0.3%Nd@NaGdF4@NaGdF4:10%Yb/1%Er@NaGdF4:10%Yb @NaNdF4:10%Yb multiple core-shell structure. Here the inert two layers (NaGdF4 and NaGdF4:10%Yb) can substantially eliminate the quenching effects, thus achieving markedly enhanced NIR-to-NIR DCL, NIR-to-Vis up-conversion luminescence (UCL), and thermal effect under a single 808 nm light excitation simultaneously. The UCL excites the attached photosensitive drug (Au25 nanoclusters) to generate singlet oxygen ((1)O2) for photodynamic therapy (PDT), while DCL with strong NIR emission serves as probe for sensitive deep-tissue imaging. The in vitro and in vivo experimental results demonstrate the excellent cancer inhibition efficacy of this platform due to a synergistic effect arising from the combined PTT and PDT. Furthermore, multimodal imaging including fluorescence imaging (FI), photothermal imaging (PTI), and photoacoustic imaging (PAI) has been obtained, which is used to monitor the drug delivery process, internal structure of tumor and photo-therapeutic process, thus achieving the target of imaging-guided cancer therapy.

Au25 cluster functionalized metal-organic nanostructures for magnetically targeted photodynamic/photothermal therapy triggered by single wavelength 808 nm near-infrared light.

Near-infrared (NIR) light-induced cancer therapy has gained considerable interest, but pure inorganic anti-cancer platforms usually suffer from degradation issues. Here, we designed metal-organic frameworks (MOFs) of Fe3O4/ZIF-8-Au25 (IZA) nanospheres through a green and economic procedure. The encapsulated Fe3O4 nanocrystals not only produce hyperthemal effects upon NIR light irradiation to effectively kill tumor cells, but also present targeting and MRI imaging capability. More importantly, the attached ultrasmall Au25(SR)18(-) clusters (about 2.5 nm) produce highly reactive singlet oxygen ((1)O2) to cause photodynamic effects through direct sensitization under NIR light irradiation. Furthermore, the Au25(SR)18(-) clusters also give a hand to the hyperthemal effect as photothermal fortifiers. This nanoplatform exhibits high biocompatibility and an enhanced synergistic therapeutic effect superior to any single therapy, as verified by in vitro and in vivo assay. This image-guided therapy based on a metal-organic framework may stimulate interest in developing other kinds of metal-organic materials with multifunctionality for tumor diagnosis and therapy.

Y2O3:Yb,Er@mSiO2-Cu(x)S double-shelled hollow spheres for enhanced chemo-/photothermal anti-cancer therapy and dual-modal imaging.

Multifunctional composites have gained significant interest due to their unique properties which show potential in biological imaging and therapeutics. However, the design of an efficient combination of multiple diagnostic and therapeutic modes is still a challenge. In this contribution, Y2O3:Yb,Er@mSiO2 double-shelled hollow spheres (DSHSs) with up-conversion fluorescence have been successfully prepared through a facile integrated sacrifice template method, followed by a calcination process. It is found that the double-shelled structure with large specific surface area and uniform shape is composed of an inner shell of luminescent Y2O3:Yb,Er and an outer mesoporous silica shell. Ultra small Cu(x)S nanoparticles (about 2.5 nm) served as photothermal agents, and a chemotherapeutic agent (doxorubicin, DOX) was then attached onto the surface of mesoporous silica, forming a DOX-DSHS-Cu(x)S composite. The composite exhibits high anti-cancer efficacy due to the synergistic photothermal therapy (PTT) induced by the attached Cu(x)S nanoparticles and the enhanced chemotherapy promoted by the heat from the Cu(x)S-based PTT when irradiated by 980 nm near-infrared (NIR) light. Moreover, the composite shows excellent in vitro and in vivo X-ray computed tomography (CT) and up-conversion fluorescence (UCL) imaging properties owing to the doped rare earth ions, thus making it possible to achieve the target of imaging-guided synergistic therapy.

An imaging-guided platform for synergistic photodynamic/photothermal/chemo-therapy with pH/temperature-responsive drug release.

To integrate biological imaging and multimodal therapies into one platform for enhanced anti-cancer efficacy, we have designed a novel core/shell structured nano-theranostic by conjugating photosensitive Au25(SR)18 - (SR refers to thiolate) clusters, pH/temperature-responsive polymer P(NIPAm-MAA), and anti-cancer drug (doxorubicin, DOX) onto the surface of mesoporous silica coated core-shell up-conversion nanoparticles (UCNPs). It is found that the photodynamic therapy (PDT) derived from the generated reactive oxygen species and the photothermal therapy (PTT) arising from the photothermal effect can be simultaneously triggered by a single 980 nm near infrared (NIR) light. Furthermore, the thermal effect can also stimulate the pH/temperature sensitive polymer in the cancer sites, thus realizing the targeted and controllable DOX release. The combined PDT, PTT and pH/temperature responsive chemo-therapy can markedly improve the therapeutic efficacy, which has been confirmed by both in intro and in vivo assays. Moreover, the doped rare earths endow the platform with dual-modal up-conversion luminescent (UCL) and computer tomography (CT) imaging properties, thus achieving the target of imaging-guided synergistic therapy under by a single NIR light.

LaF3:Ln mesoporous spheres: controllable synthesis, tunable luminescence and application for dual-modal chemo-/photo-thermal therapy.

In this report, uniform LaF(3):Ln mesoporous spheres have been synthesized by a facile and mild in situ ion-exchange method using yolk-like La(OH)3:Ln mesoporous spheres as templates, which were prepared through a self-produced bubble-template route. It was found that the structures of the final LaF(3):Ln can simply be tuned by adding a polyetherimide (PEI) reagent. LaF(3):Ln hollow mesoporous spheres (HMSs) and LaF(3):Ln flower-like mesoporous spheres (FMSs) were obtained when assisted by PEI and in the absence of PEI. The up-conversion (UC) luminescence results reveal that the doping of Nd(3+) ions in LaF(3):Ln can markedly influence the UC emissions of the products. It is interesting that an obvious thermal effect is achieved due to the energy back-transfer from Tm(3+) to Nd(3+) ions under 980 nm near-infrared (NIR) irradiation. The LaF(3):Yb/Er/Tm/Nd HMSs show good biocompatibility and sustained doxorubicin (DOX) release properties. In particular, upon 980 nm NIR irradiation, the photothermal effect arising from the Nd(3+) doping induces a faster DOX release from the drug release system. Moreover, UC luminescence images of LaF(3):Yb/Er/Tm/Nd HMSs uptaken by MCF-7 cells exhibit apparent green emission under 980 nm NIR irradiation. Such a multifunctional carrier combining UC luminescence and hyperthermia with the chemotherapeutic drugs should be of high potential for the simultaneous anti-cancer therapy and cell imaging.