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.

Deep Insight of Design, Mechanism, and Cancer Theranostic Strategy of Nanozymes.

Since the discovery of enzyme-like activity of Fe3O4 nanoparticles in 2007, nanozymes are becoming the promising substitutes for natural enzymes due to their advantages of high catalytic activity, low cost, mild reaction conditions, good stability, and suitable for large-scale production. Recently, with the cross fusion of nanomedicine and nanocatalysis, nanozyme-based theranostic strategies attract great attention, since the enzymatic reactions can be triggered in the tumor microenvironment to achieve good curative effect with substrate specificity and low side effects. Thus, various nanozymes have been developed and used for tumor therapy. In this review, more than 270 research articles are discussed systematically to present progress in the past five years. First, the discovery and development of nanozymes are summarized. Second, classification and catalytic mechanism of nanozymes are discussed. Third, activity prediction and rational design of nanozymes are focused by highlighting the methods of density functional theory, machine learning, biomimetic and chemical design. Then, synergistic theranostic strategy of nanozymes are introduced. Finally, current challenges and future prospects of nanozymes used for tumor theranostic are outlined, including selectivity, biosafety, repeatability and stability, in-depth catalytic mechanism, predicting and evaluating activities.

Association of BIRC5 Gene Polymorphism with the Collateral Circulation and Severity of Large Artery Atherosclerotic Stroke.

Objectives: The collateral circulation near the cerebral artery occlusion can contribute to the relief of the symptoms and signs of stroke. Genetic factors play a decisive role in the difference in collateral circulation. Survivin, encoded by the baculoviral inhibitor of apoptosis (IAP) repeat-containing 5 gene (BIRC5), plays an important role in maintaining long-term endothelial integrity and homeostasis and as an angiogenic factor in the treatment of vascular diseases. We hypothesized that genetic variations in the BIRC5 gene may contribute to severity by influencing the collateral circulation. This study aimed at examining how the polymorphism of the BIRC5 gene correlated with the collateral circulation and severity of large artery atherosclerotic stroke. Methods: This study enrolled 428 patients with large artery atherosclerotic stroke. There are no statistical differences in age, sex, social behavior, such as smoking and drinking, between the groups classified by the collateral circulation and by the severity of stroke (P > 0.01). Direct sequencing was performed for the genotyping of single nucleotide polymorphism (SNP) of BIRC5 (rs2071214). The enrolled patients were divided into several subgroups based on the collateral flow grading system from the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR), the results of the National Institutes of Health Stroke Survey (NIHSS) (6 as a threshold), and the score of the modified Rankin scale (mRS) (for the prediction of prognosis, 2 as a threshold). Differences among subgroups were identified through logistic regression. Results: The analysis of collateral circulation revealed the significant correlation of SNP of rs2071214 with the development of poor collateral circulation of large artery atherosclerotic stroke in the additive model (GG vs. AA, odds ratio (OR) = 3.592, 95% confidence interval (CI) = 1.410-9.150, and P=0.007) and the recessive model (GG vs. AA/GA, OR = 3.313, 95% CI = 1.420-7.727, and P=0.006). The analysis of stroke severity exposed the significant role of the SNP of rs2071214 in increasing stroke severity in the dominant model (GA/GG vs. AA, OR = 1.658, 95% CI = 1.017-2.703, and P=0.043) and the additive model (GA vs. AA, OR = 1.717, 95% CI = 1.021-2.888, and P=0.042). However, the analysis of the short-term outcome indicated that three genetic models were not associated with short-term outcomes in the additive model (GA vs. AA, P=0.815, GG vs. AA, and P=0.336), the dominant model (GA/GG vs. AA and P=0.589), and the recessive model (GG vs. AA/GA and P=0.342). Conclusion: Our findings identified the SNP of rs2071214 of the BIRC5 gene as a risk factor for the poor compensatory ability of collateral circulation and a predictor of stroke severity in large artery atherosclerotic stroke, which suggested that the SNP of rs2071214 can serve as an innovative therapeutic target for patients with acute ischemic stroke.

Engineering oxygen vacancy of MoOx nanoenzyme by Mn doping for dual-route cascaded catalysis mediated high tumor eradication.

There is an urgent need to develop photosensitive nanoenzymes with better phototherapeutic efficiency through simple processes. By exploiting semiconductor catalysis and defect chemistry principles, herein, a MnMoOx composite semiconductor nanoenzyme was developed to achieve a fully integrated theranostic nanoenzyme for highly efficient photo/chemo-enzyme-dynamic eradication of deep tumors. Relative to iron oxides, manganese oxides offer ideal catalytic performance under near-neutral conditions, which helps to broaden the suitable pH range of the MnMoOx nanoenzyme for antitumor therapy. Furthermore, with the assistance of glutathione depletion, Mn4+/Mo6+ was successfully converted to Mn2+/Mo5+, inhibiting the scavenging of reactive oxygen species (ROS) and promoting cycling. Therefore, MnMoOx has favorable catalase (CAT)-like activity and oxidase (OXD)-like activity in the tumor microenvironment (TME) for promoting the "H2O2O2O2-" and "H2O2OH" cascade reactions. The abundant oxygen vacancy defects also promote the surface plasmon resonance (SPR) effect in the second near-infrared (NIR-II) window of MnMoOx, which significantly enhanced its photothermal therapy (PTT) effect and catalytic activity. In detail, ROS production was significantly enhanced due to the adsorption of water and oxygen molecules by the rich oxygen vacancies of MnMoOx. MnMoOx also exhibited excellent multi-modal imaging activity (including computed tomography (CT), magnetic resonance imaging (MRI), and photoacoustic (PA)), which can be exploited to better guide the administration of medication.

CuFeSe2-based thermo-responsive multifunctional nanomaterial initiated by a single NIR light for hypoxic cancer therapy.

Integration of various therapeutic modes and novel hypoxic therapy are two emerging aspects in the current anti-cancer field. Based on this, we designed a multifunctional therapeutic system combining photothermal therapy (PTT), the newly defined chemodynamic therapy (CDT) and AIPH-based hypoxic therapy ingeniously, which can take effect well in hypoxic tumor environments. The CuFeSe2-based heterojunction was controllably constructed by the coating of a MIL-100(Fe) shell layer by layer, and the large mesoporous cavities were subsequently filled with a polymerization initiator (AIPH) and phase change material (tetradecanol) to achieve higher drug loading and controlled heat release of radicals. When irradiated by a single 808 nm laser, the photothermal agent of CuFeSe2 plays a significant role of the initiating switch in the whole nanoplatform, whose hyperthermia not only realizes fundamental PTT but also promotes greatly the Fenton reaction of the MIL-100(Fe) shell for oxidative ˙OH production and the generation of toxic AIPH radicals while melting tetradecanol. Due to the sensitive heat-responsive therapies independent of oxygen concentration, the nanoplatform showed a superior therapeutic effect for hypoxic tumor environments. Besides, on account of the effective attenuation for X-rays and the presence of the magnetic element Fe of CuFeSe2, the nanoplatform was also certified to be a superior diagnosis agent for computed tomography (CT) and magnetic resonance imaging (MRI). As expected, cell experiments in vitro and mice experiments in vivo further verified the excellent biocompatibility and antitumor effect, suggesting that this nanoplatform of CuFeSe2@MIL-100(Fe)-AIPH is promising for simultaneous diagnosis and treatment in hypoxic cancer therapy.

Correction: Y2O3:Yb,Er@mSiO2-CuxS double-shelled hollow spheres for enhanced chemo-/photothermal anti-cancer therapy and dual-modal imaging.

Correction for 'Y2O3:Yb,Er@mSiO2-CuxS double-shelled hollow spheres for enhanced chemo-/photothermal anti-cancer therapy and dual-modal imaging' by Dan Yang et al., Nanoscale, 2015, 7, 12180-12191, DOI: 10.1039/C5NR02269J.

Upconversion-mediated ZnFe2O4 nanoplatform for NIR-enhanced chemodynamic and photodynamic therapy.

ZnFe2O4, a semiconductor catalyst with high photocatalytic activity, is ultrasensitive to ultraviolet (UV) light and tumor H2O2 for producing reactive oxygen species (ROS). Thereby, ZnFe2O4 can be used for photodynamic therapy (PDT) from direct electron transfer and the newly defined chemodynamic therapy (CDT) from the Fenton reaction. However, UV light has confined applicability because of its high phototoxicity, low penetration, and speedy attenuation in the biotissue. Herein, an upconversion-mediated nanoplatform with a mesoporous ZnFe2O4 shell was developed for near-infrared (NIR) light enhanced CDT and PDT. The nanoplatform (denoted as Y-UCSZ) was comprised of upconversion nanoparticles (UCNPs), silica shell, and mesoporous ZnFe2O4 shell and was synthesized through a facile hydrothermal method. The UCNPs can efficiently transfer penetrable NIR photons to UV light, which can activate ZnFe2O4 for producing singlet oxygen thus promoting the Fenton reaction for ROS generation. Besides, Y-UCSZ possesses enormous internal space, which is highly beneficial for housing DOX (doxorubicin, a chemotherapeutic agent) to realize chemotherapy. Moreover, the T 2-weighted magnetic resonance imaging (MRI) effect from Fe3+ and Gd3+ ions in combination with the inherent upconversion luminescence (UCL) imaging and computed tomography (CT) from the UCNPs makes an all-in-one diagnosis and treatment system. Importantly, in vitro and in vivo assays authenticated excellent biocompatibility of the PEGylated Y-UCSZ (PEG/Y-UCSZ) and high anticancer effectiveness of the DOX loaded PEG/Y-UCSZ (PEG/Y-UCSZ&DOX), indicating its potential application in the cancer treatment field.

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.

A smart tumor microenvironment responsive nanoplatform based on upconversion nanoparticles for efficient multimodal imaging guided therapy.

Near-infrared (NIR) light-induced imaging-guided cancer therapy has been studied extensively in recent years. Herein, we report a novel theranostic nanoplatform by modifying polyoxometalate (POM) nanoclusters onto mesoporous silica-coated upconversion nanoparticles (UCNPs), followed by loading doxorubicin (DOX) in the mesopores and coating a folate-chitosan shell onto the surface. In this nanoplatform, the core-shell structured UCNPs (NaYF4:Yb,Er@NaYF4:Yb,Nd) showed special upconverting luminescence (UCL) when irradiated with high-penetration 808 nm NIR light, and the doped Yb and Nd ions endowed the sample with CT imaging properties, thus achieving a dual-mode imaging function. Moreover, the simultaneously generated heat mediated by the 808 nm NIR light may coordinate with the chemotherapy generated from the released DOX to realize an efficient synergistic therapy, verified by diverse in vitro and in vivo assays. The coated folate-chitosan shell can target the platform to tumor tissues when it was transported in the blood vessels and accumulated in tumor sites via the enhanced permeability and retention effect (EPR). Due to the acidic and reductive microenvironment of the tumor, the DOX released quickly with the dissolved folate-chitosan shell, exhibiting obvious tumor microenvironment (TME) responsive properties. The smart imaging-guided therapeutic nanoplatform should be highly promising in TME responsive therapy.

Folic Acid Functionalized Zirconium-Based Metal-Organic Frameworks as Drug Carriers for Active Tumor-Targeted Drug Delivery.

Nanoscale metal-organic frameworks (NMOFs) have proven to be a class of promising drug carriers as a result of their high porosity, crystalline nature with definite structure information, and potential for further functionality. However, MOF-based drug carriers with active tumor-targeting function have not been extensively researched until now. Here we show a strategy for constructing active tumor-targeted NMOF drug carriers by anchoring functional folic acid (FA) molecules onto the metal clusters of NMOFs. Two zirconium-based MOFs, MOF-808 and NH2 -UiO-66, were chosen as models to reduce to the nanoscale for application as drug carriers, and then the terminal carboxylates of FA molecules were coordinated to Zr6 clusters on the surfaces of the nanoparticles by substitution of the original formate or terminal -OH ligands. The successful modification with FA was confirmed by solid-state 13 C MAS NMR and UV/Vis spectroscopy and other characterization methods. Drug loading and controlled release behavior at different pH were determined by utilizing the anticancer drug 5-fluorouracil (5-FU) as the model drug. Confocal laser scanning microscopy measurements further demonstrated that 5-FU-loaded FA-NMOFs have excellent targeting ability through the efficient cellular uptake of FA-NMOFs. This work opens up a new avenue to the construction of active tumor-targeted NMOF-based drug carriers with potential for cancer therapies.

Carbon-Dot-Decorated TiO2 Nanotubes toward Photodynamic Therapy Based on Water-Splitting Mechanism.

The use of visible light to produce reactive oxygen species (ROS) from renewable water splitting is a highly promising means in photodynamic therapy (PDT). Up to date, diverse inorganic-organic hybrid materials developed as photosensitizers still undergo low therapeutic efficiency and/or poor stability. Herein, a kind of carbon-nanodot-decorated TiO2 nanotubes (CDots/TiO2 NTs) composite is developed and applied for photodynamic therapy. Upon 650 nm laser light excitation, the emissions with short wavelengths (325-425 nm) from the CDots as a result of upconversion process excite TiO2 NTs to form electron/hole (e- /h+ ) pairs, triggering the reaction with the adsorbed oxidants to produce ROS. Moreover, the CDots deposited on the surface of TiO2 NTs markedly enhance the light absorption response and narrow the band gap compared with anatase TiO2 nanoparticles, thereby increasing the photosensitizing efficiency. Besides, the CDots show high chemical catalytic activity for H2 O2 decomposition even if no light is needed, which is essential for PDT. The excellent therapeutic performance actuated by 650 nm light is demonstrated by in vitro and in vivo assays. This photosensitizer comprises low-cost, earth-abundant, environment-friendly merits, and especially excellent stability, implying its feasible application in biomedical field.

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.

Au Nanoclusters Sensitized Black TiO2-x Nanotubes for Enhanced Photodynamic Therapy Driven by Near-Infrared Light.

The low reactive oxygen species production capability and the shallow tissue penetration of excited light (UV) are still two barriers in photodynamic therapy (PDT). Here, Au cluster anchored black anatase TiO2-x nanotubes (abbreviated as Au25 /B-TiO2-x NTs) are synthesized by gaseous reduction of anatase TiO2 NTs and subsequent deposition of noble metal. The Au25 /B-TiO2-x NTs with thickness of about 2 nm exhibit excellent PDT performance. The reduction process increased the density of Ti3+ on the surface of TiO2 , which effectively depresses the recombination of electron and hole. Furthermore, after modification of Au25 nanoclusters, the PDT efficiency is further enhanced owing to the changed electrical distribution in the composite, which forms a shallow potential well on the metal-TiO2 interface to further hamper the recombination of electron and hole. Especially, the reduction of anatase TiO2 can expend the light response range (UV) of TiO2 to the visible and even near infrared (NIR) light region with high tissue penetration depth. When excited by NIR light, the nanoplatform shows markedly improved therapeutic efficacy attributed to the photocatalytic synergistic effect, and promotes separation or restrained recombination of electron and hole, which is verified by experimental results in vitro and in vivo.

A Versatile Near Infrared Light Triggered Dual-Photosensitizer for Synchronous Bioimaging and Photodynamic Therapy.

Photodynamic therapy (PDT) based on Tm3+-activated up-conversion nanoparticles (UCNPs) can effectively eliminate tumor cells by triggering inorganic photosensitizers to generate cytotoxic reactive oxygen species (ROS) upon tissue penetrating near-infrared (NIR) light irradiation. However, the partial use of the emitted lights from UCNPs greatly hinders their application. Here we develop a novel dual-photosensitizer nanoplatform by coating mesoporous graphitic-phase carbon nitride (g-C3N4) layer on UCNPs core, followed by attaching ultrasmall Au25 nanoclusters and PEG molecules (named as UCNPs@g-C3N4-Au25-PEG). The ultraviolet-visible (UV-vis) light and the intensive near infrared (NIR) emission from UCNPs can activate g-C3N4 and excite Au25 nanoclusters to produce ROS, respectively, and thus realize the simultaneous activation of two kinds of photosensitizers for enhanced the efficiency of PDT mediated by a single NIR light excitation. A markedly higher PDT efficacy for the dual-photosensitizer system than any single modality has been verified by the enhanced ROS production and in vitro and in vivo results. By combining the inherent multi-imaging properties (up-conversion, CT, and MRI) of UCNPs, an imaging guided therapeutic platform has been built. As the first report of dual-inorganic-photosensitizer PDT agent, our developed system may be of high potential in future NIR light induced PDT application.

Multiple imaging and excellent anticancer efficiency of an upconverting nanocarrier mediated by single near infrared light.

It is difficult to meet the requirements of clinical diagnosis through a single imaging technique. Similarly, satisfactory therapy efficacy is also hard to achieve by a single therapeutic modality. It is therefore highly desirable and interesting to simultaneously achieve multimodal imaging and therapies in one single structure. In this study, we developed a core-shell-satellite NaGdF4:Yb,Er,Mn,Co@mSiO2-CuS structure using up-conversion luminescent (UCL) NaGdF4:Yb,Er,Mn,Co as the core, mesoporous silica as the layer, and the photoactive CuS nanoparticles as the satellites. The further linked photosensitizer (ZnPc) and doxorubicin hydrochloride (DOX) allow the system to have photodynamic therapy (PDT) and chemotherapy functions. The doping of Co2+ ions in the core endows the carrier with T2-weighted magnetic resonance imaging (MRI) properties, and the co-doping of Mn2+ ions can efficiently enhance the red emission which further improves the PDT efficiency by reacting with the attached ZnPc upon near-infrared (NIR) light irradiation. The nanoplatform exhibits excellent anti-tumor efficiency due to a synergistic effect arising from combined PDT, photo-thermal therapy (PTT) and chemotherapy, which has been evidenced by in vitro and in vivo results. Due to the multimodal imaging (MRI, CT, and UCL) properties, the drug delivery process and therapeutic efficacy can be monitored in real time and assessed, thus achieving the target of imaging-guided therapy.

Multifunctional Theranostics for Dual-Modal Photodynamic Synergistic Therapy via Stepwise Water Splitting.

Combined therapy using multiple approaches has been demonstrated to be a promising route for cancer therapy. To achieve enhanced antiproliferation efficacy under hypoxic condition, here we report a novel hybrid system by integrating dual-model photodynamic therapies (dual-PDT) in one system. First, we attached core-shell structured up-conversion nanoparticles (UCNPs, NaGdF4:Yb,Tm@NaGdF4) on graphitic-phase carbon nitride (g-C3N4) nanosheets (one photosensitizer). Then, the as-fabricated nanocomposite and carbon dots (another photosensitizer) were assembled in ZIF-8 metal-organic frameworks through an in situ growth process, realizing the dual-photosensitizer hybrid system employed for PDT via stepwise water splitting. In this system, the UCNPs can convert deep-penetration and low-energy near-infrared light to higher-energy ultraviolet-visible emission, which matches well with the absorption range of the photosensitizers for reactive oxygen species (ROS) generation without sacrificing its efficacy under ZIF-8 shell protection. Furthermore, the UV light emitted from UCNPs allows successive activation of g-C3N4 and carbon dots, and the visible light from carbon dots upon UV light excitation once again activate g-C3N4 to produce ROS, which keeps the principle of energy conservation thus achieving maximized use of the light. This dual-PDT system exhibits excellent antitumor efficiency superior to any single modality, verified vividly by in vitro and in vivo assay.

NIR-driven water splitting by layered bismuth oxyhalide sheets for effective photodynamic therapy.

Two major issues of finding the appropriate photosensitizer and raising the penetration depth of irradiation light exist in further developing of photodynamic therapy (PDT). The excited ultraviolet/visible (UV/vis) irradiation light has a relatively shallow depth of penetration and UV light itself may have sufficient energy to damage normal tissues; these are substantial limitations to successful cancer therapy. Herein, we for the first time report a novel multifunctional nanoplatform for a single 980 nm near-infrared (NIR) light-triggered PDT based on NaGdF4:Yb,Tm@NaGdF4 upconversion nanoparticles (UCNPs) integrated with bismuth oxyhalide (BiOCl) sheets, designated as UCNPs@BiOCl. And UCNPs@BiOCl was fabricated by a convenient, efficient, green, and inexpensive method. Excitingly, layered bismuth oxyhalide materials possess a high photocatalytic performance, unique layered structures and wide light response to a broad wavelength range of ultraviolet to visible light. And the loaded UCNPs can convert NIR light into UV/vis region emissions, which drives the pure water splitting of BiOCl sheets to produce plenty of reactive oxygen species (ROS) to damage tumor cells. The excellent antitumor efficiency of the complex has been evidently attested by comparing experimental results. Our work may make a contribution to the wide application of BiOCl-based materials in biomedicine.

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.

Doxorubicin-conjugated CuS nanoparticles for efficient synergistic therapy triggered by near-infrared light.

To integrate photothermal therapy (PTT) with chemotherapy for improving anticancer efficiency, we developed a novel and multifunctional doxorubicin (DOX) conjugated copper sulfide nanoparticle (CuS-DOX NP) drug delivery system using hydrazone bonds to conjugate carboxyl-functionalized copper sulfide nanoparticles (CuS NPs) and DOX. On the other hand, the hydrazone bonds could be used for improving the DOX release rate (88.0%) by cleavage in a mildly acidic environment irradiated by 808 nm laser light, which could greatly promote chemo-therapeutic efficacy. Simultaneously, CuS NPs which can absorb near infrared (NIR) light produce a clear thermal effect, giving rise to a synergistic therapeutic effect combined with enhanced chemo-therapy. The DOX-conjugated CuS NPs display an evident in vitro cytotoxicity to HeLa cancer cells under 808 nm light irradiation. High tumor inhibition efficacy has been achieved after 14 day in vivo treatment, performed with intravenous administration of CuS-DOX NPs with 808 nm laser irradiation on H22 tumor-bearing mice. The multifunctional system which was achieved by a facile route should be a potential candidate in the anti-cancer field due to the synergistic therapeutic effect, which is superior to any single approach.

NIR-driven graphitic-phase carbon nitride nanosheets for efficient bioimaging and photodynamic therapy.

Photodynamic therapy (PDT) is a noninvasive and promising anticancer therapy modality that utilizes the photochemical reactions of photosensitizers, upon irradiation at a specific wavelength, to yield reactive oxygen species (ROS) to impair malignant cancer cells. As a potential and new two-dimensional layered photosensitizer, graphitic-phase carbon nitride (g-C3N4) exhibits a high blue photoluminescence quantum yield and good biocompatibility, but is challenged by limited narrow absorption in the near-infrared (NIR) region. Herein, in order to broaden its light utilization, unique and original NIR light excited nanocomposites (g-C3N4/UCNP NCs) for PDT based on g-C3N4 nanosheets combined with up-conversion nanoparticles (UCNPs) have been designed. UCNPs can efficiently convert NIR light to ultraviolet and visible light emissions that match well with the absorption of g-C3N4 nanosheets. The nanocomposites swallowed up by cancer cells are able to yield ROS and suppress tumor cell growth and then induce apoptosis upon NIR laser excitation. This demonstrates the potential of g-C3N4/UCNP NCs as a low-toxic and biocompatible photosensitizer for PDT and for down/up-conversion luminescence imaging.