Search

The emergence of X-ray-induced photodynamic therapy (X-PDT) holds tremendous promise for clinical deep-penetrating cancer therapy. However, the clinical application of X-PDT in cancer treatment is still limited due to the hypoxic property of cancerous tissue, the inherent antioxidant system of tumor cells, and the difficulty in matching the absorption spectra of photosensitizers. Herein, a versatile core-shell radiosensitizer (SCNPs@DMSN@CeO

The development of a manageable reactive nitrogen species-potentiated nitrosative stress induction system for cancer therapy has remained elusive. Herein, tailored silica-based nanoscintillators were reported for low-dosage X-ray boosting for the in situ formation of highly cytotoxic peroxynitrite (ONOO

The abrogation of the self-adaptive redox evolution of tumors is promising for improving therapeutic outcomes. In this study, we designed a novel trimetallic alloy nanozyme AuCuPt-PpIX (ACPP), which mimics up to five naturally occurring enzymes—glucose oxidase (GOD), superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and glutathione peroxidase (GPx). Facilitated by these enzyme-mimicking traits, the constructed ACPP nanozymes can not only disrupt the established redox homeostasis in tumors through a series of enzymatic cascade reactions but also achieve cyclic regeneration of the relevant enzyme substrates. Density functional theory (DFT) calculations have theoretically explained the synergistic effect of multi-metallic doping and the possible mechanism of enzymatic catalysis. The doped Cu and Pt sites are conducive to the adsorption, activation, and dissociation of reactant molecules, whereas the Au sites are conducive to desorption, which significantly improves catalytic efficiency via a synergistic effect. Additionally, ACPP nanozymes can improve the effect of protoporphyrin (PpIX)-enabled sonodynamic therapy (SDT) by alleviating hypoxia and initiating ferroptosis by inducing lipid peroxidation (LPO) and inhibiting GPX4 activity, thus achieving multi-modal synergistic therapy. This study presents a typical paradigm to enable the use of multi-metallic alloy nanozymes for the treatment of tumor cells with self-adaptive properties.

Recently, various metal peroxide nanomaterials have drawn increasing attention as an efficient hydrogen peroxide (H

Immune checkpoint blockade (ICB) therapy has attracted widespread attention in cancer treatment. Due to the low immunogenicity and immune suppression state in the tumor microenvironment (TME), the therapeutic effects are only moderate. Herein, a TME-activable manganese-boosted catalytic immunotherapy is designed for synergism with ICB therapy to kill tumors efficiently. The tumor cell membrane (CM)-wrapping multienzyme-mimic manganese oxide (MnO

Mitochondria are the "power plant" of the cell, providing a constant source of energy, and are involved in a variety of intracellular signaling pathways. Among these pathways, Ca2+ homeostasis is closely related to the normal function of mitochondria. By destroying the Ca2+ steady state of mitochondria and disrupting their multiple cellular activities, tumor cell killing can be achieved. In addition, the presence of an intracellular oxidative stress state triggers the closure of cellular calcium channels, which leads to intracellular Ca2+ retention and enrichment. We designed a targeted and tumor microenvironment (TME)-responsive CaO2-based nanosystem that can selectively target cancer cells for pH-controlled degradation and drug release, alter cellular physiological mechanisms by disrupting Ca2+ homeostasis in an artificial manner, and introduce mitochondrial Ca2+ excess-mediated apoptosis. Meanwhile, the production of Ca(OH)2 will raise the pH of the microenvironment and subsequently promote the oxidation process of glutathione by H2O2 released from CaO2 degradation, achieving the goal of remodeling TME. Moreover, calcium overload of tumor cells and calcification of tissues can both inhibit tumor growth and act as a contrast agent for computed tomography imaging.

Nanosystem-mediated tumor radiosensitization strategy combining the features of X-ray with infinite penetration depth and high atomic number elements shows considerable application potential in clinical cancer therapy. However, it is difficult to achieve satisfactory anticancer efficacy using clinical radiotherapy for the majority of solid tumors due to the restrictions brought about by the tumor hypoxia, insufficient DNA damage, and rapid DNA repair during and after treatment. Inspired by the complementary advantages of nitric oxide (NO) and X-ray-induced photodynamic therapy, we herein report a two-dimensional nanoplatform by the integration of the NO donor-modified LiYF4:Ce scintillator and graphitic carbon nitride nanosheets for on-demand generation of highly cytotoxic peroxynitrite (ONOO–). By simply adjusting the Ce3+ doping content, the obtained nanoscintillator can realize high radioluminescence, activating photosensitive materials to simultaneously generate NO and superoxide radical for the formation of ONOO– in the tumor. Obtained ONOO– effectively amplifies therapeutic efficacy of radiotherapy by directly inducing mitochondrial and DNA damage, overcoming hypoxia-associated radiation resistance. The level of glutamine synthetase (GS) is downregulated by ONOO–, and the inhibition of GS delays DNA damage repair, further enhancing radiosensitivity. This work establishes a combinatorial strategy of ONOO– to overcome the major limitations of radiotherapy and provides insightful guidance to clinical radiotherapy. Agency for Science, Technology and Research (A*STAR) Submitted/Accepted version Financial support from the National Natural Science Foundation of China (51972075, 51972076, and 51772059), the Natural Science Foundation of Shandong Province (ZR2019ZD29), the Natural Science Foundation of Heilongjiang Province (YQ2019E014), the Postdoctoral Scientific Research Developmental Fund (LBH-Q18034), and the Ph.D. Student Research and Innovation Fund of the Fundamental Research Funds for the Central Universities (3072020GIP1016) are greatly acknowledged. This research is also supported by the Singapore Agency for Science, Technology and Research (A*STAR) AME IRG grant (A20E5c0081).

Mild photothermal therapy (PTT,45 °C) can prevent tumor metastasis and heat damage to normal tissue, compared with traditional PTT (50 °C). However, its therapeutic efficacy is limited owing to the hypoxic tumor environment and tumor thermoresistance owing to the overproduction of heat shock proteins (HSPs). Herein, a near-infrared (NIR)-triggered theranostic nanoplatform (GA-PB@MONs@LA) is designed for synergistic mild PTT and enhanced Fenton nanocatalytic therapy against hypoxic tumors. The nanoplatform is fabricated by the confined formation of Prussian blue (PB) nanoparticles in mesoporous organosilica nanoparticles (MONs), followed by the loading of gambogic acid (GA), an HSP90 inhibitor, and coating with thermo-sensitive lauric acid (LA). Upon NIR irradiation, the photothermal effect (44 °C) of PB not only induces apoptosis of tumor cells but also triggers the on-demand release of GA, inhibiting the production of HSP90. Moreover, the delivered heat simultaneously enhances the catalase-like and Fenton activity of PB@MONs@LA in an acidic tumor microenvironment, relieving the tumor hypoxia and promoting the generation of highly toxic •OH. In addition, the nanoplatform enables magnetic resonance/photoacoustic dual-modal imaging. Thus, this study describes a distinctive paradigm for the development of NIR-triggered theranostic nanoplatforms for enhanced cancer therapy.

Although nanocatalytic therapy has become an emerging strategy for tumor treatment, the therapeutic effects of reactive oxygen species (ROS)-mediated treatment are still seriously limited by the inherent flaws of the enzymatic activities and the specific physicochemical properties of the tumor microenvironment (TME). Herein, we report an ultrasmall bimetallic oxide nanozyme (CuFe

The endogenous tumor microenvironment (TME) can signally influence the therapeutic effects of cancer, so it is necessary to explore effective synergistic therapeutic strategies based on changing of the TME. Here, a catalytic cascade nanoplatform based on manganese (Mn)-etched dendritic mesoporous silicon nanoparticles (designated as DMMnSiO3 NPs) loaded with indocyanine green (ICG) and natural glucose oxidase (GOD) is established (designated as DIG nanocomposites). As the Mn-O bonds in DMMnSiO3 NPs are susceptive to mildly acidic and reducing environments, the DIG nanocomposites can be rapidly decomposed because of the biodegradation of DMMnSiO3 NPs once internalized into the tumor by the consumption of glutathione (GSH) in TME to weaken the antioxidant capability of the tumors. The released Mn2+ could catalyze endogenous hydrogen peroxide (H2O2) to generate oxygen (O2) to relieve the hypoxia in TME. The generation of O2 may promote the catalyzed oxidation of glucose by GOD, which will cut off nutrient supplies, accompanied by the regeneration of H2O2. The regenerated H2O2 could be sequentially catalyzed by Mn2+ to compensate for the consumed O2, and thus, the catalytic cascade process between Mn2+ and GOD was set up. As a result, a synergistic therapeutic strategy based on T1-weighted magnetic resonance imaging (MRI) of Mn2+, starvation therapy by O2-compensation enhanced catalyzing glucose, dual-model (GSH consumption and O2 compensation) enhanced photodynamic therapy, and effective photothermal therapy of ICG (η = 23.8%) under 808 nm laser irradiation has been successfully established.

The development of a stimulus-responsive nanosystem provides an effective method for improving the accuracy and efficiency of chemotherapy. Meanwhile, traditional photodynamic therapy (PDT) has been substantially restricted by the low dosage of photosensitizer and limited penetration depth of the ultraviolet (UV) or visible light used for excitation. Here, we designed a smart multifunctional nanoplatform by coating core-shell composite mesoporous silica-encapsulated upconversion nanoparticles and chlorin e6 (Ce6) with degradable calcium phosphate, followed by the loading of doxorubicin (DOX). In our structure, the as-synthesized nanoplatform exhibits high responsiveness to a low pH value and degrades rapidly in the weakly acidic tumor microenvironment, allowing the quick release of loaded DOX in tumor sites. Interestingly, the loaded DOX, whose release depends on the pH value and positively correlates with the calcium-ion concentration, enables drug release to be monitored in real time. Combined with photosensitizer Ce6-induced PDT triggered by an 808 nm near-infrared light, synergistic chemo-photodynamic therapy is achieved, thus leading to a highly efficient anticancer treatment in vitro and in vivo. Importantly, the inherent properties of rare earth ions (Gd3+, Yb3+, and Nd3+) make the nanoplatform possess UCL, MRI, and CT trimode imaging capabilities, thus achieving a multiple imaging modality-guided synergistic therapy.

Clinical applications of nanozyme-initiated chemodynamic therapy (NCDT) have been severely limited by poor catalytic efficiency of nanozymes, insufficient endogenous H2O2 content, and off-target consumption. Herein, we develop hollow mesoporous Mn/Zr-co-doped CeO2 tandem nanozyme (PHMZCO-AT) with elaborately regulated multi-enzymatic activities, i.e., simultaneously enhancing superoxide dismutase (SOD)-like and peroxidase (POD)-like activities and inhibiting catalase (CAT)-like activity, serving as an H2O2 homeostasis disruptor to promote H2O2 evolvement and restrain off-target elimination of H2O2 for achieving intensive NCDT. PHMZCO-AT nanozymes with SOD-like activity can catalyze endogenous O2·– into H2O2 in the tumor region. The suppression of CAT activity and depletion of glutathione by PHMZCO-AT largely weaken the off-target decomposition of H2O2 to H2O. Elevated H2O2 is then exclusively catalyzed by the downstream POD-like activity of PHMZCO-AT to generate toxic hydroxyl radicals, further inducing tumor apoptosis and death. T1-weighted magnetic resonance imaging and high-contrast X-ray computed tomography imaging are also achieved using PEG/PHMZCO-AT nanozymes due to the existence of paramagnetic Mn2+ species and high X-ray attenuation ability of elemental Zr, permitting in vivo tracking of the therapeutic process. This work presents a powerful paradigm to achieve intensive NCDT efficacy by simultaneously regulating multi-enzymatic activities of Ce-based nanozymes and perturbing the H2O2 homeostasis in tumor microenvironment. Agency for Science, Technology and Research (A*STAR) National Research Foundation (NRF) Submitted/Accepted version The work was supported by the MOST Grant (2016YFA0101202), the National Natural Science Foundation of China (51972075 and 51772059), the Singapore Agency for Science, Technology and Research (A*STAR) AME IRG grant (A20E5c0081), the Singapore National Research Foundation Investigatorship (NRF-NRFI2018-03), and the Fundamental Research Funds for the Central Universities.

Reducing the scavenging capacity of reactive oxygen species (ROS) and elevating ROS production are two primary goals of developing novel sonosensitizers for sonodynamic therapy (SDT). Hence, ultrathin 2D Bi

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 T2-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.

Long-term tumor hypoxia has always been a huge obstacle for oxygen dependent photodynamic therapy (PDT) and anticancer drug chemotherapy. Herein, a hollow-structured biophotocatalyst was developed by coating mesoporous cerium oxide (mCeOx) on upconversion nanoparticles (UCNPs, NaGdF4:Yb,Tm@NaGdF4), and it can be initialized with a near-infrared (NIR) laser to achieve PDT with O2 compensation by decomposing the endogenous H2O2 in the tumor microenvironment. A NIR laser with a long wavelength has low phototoxicity to biotissue, and the core–inert shell structured UCNPs can efficiently convert the NIR photons into ultraviolet (UV) light, which can further trigger CeOx to produce reactive oxygen species (ROS). Moreover, the internal space of UCNPs@mCeOx is ideal for storing chemotherapeutic doxorubicin (DOX), and adequate O2 plays a key role in alleviating drug fastness via chemotherapy in hypoxic tumors, thereby strengthening the synergy between PDT and chemotherapy. After being injected into tumor-bearing mice intravenously, the nanomedicine was able to reach the tumor via an enhanced permeability and retention (EPR) effect. In addition, the capability to use the developed nanosystem in computed tomography (CT), magnetic resonance (MR) and upconversion luminescence (UCL) imaging was validated. Significantly, the NIR laser irradiated nanomedicine exhibits an excellent anticancer effect, implying promising theranostic applications.

Gasotransmitters with high therapeutic efficacy and biosafety have been drawing the attention of researchers. Nevertheless, how to effectively deliver gases to and precisely control their generation at the lesion as well as integrate them with other therapies to realize precision therapy have remained elusive. Herein, we report a versatile Cu2+-initiated nitric oxide (NO) nanocomposite for multimodal imaging-guided synergistic chemodynamic/photodynamic/gas therapy. After the nanomedicine was ingested by tumor cells, the acidic tumor microenvironment accelerated the decomposition of CuO2 and simultaneously triggered the Fenton-like catalytic reaction of Cu2+ and H2O2 to produce highly toxic ˙OH. By virtue of the NO generation and glutathione depletion, UMNOCC-PEG can relieve the antioxidant capacity and hypoxia of the tumor to improve the efficiency of chemodynamic therapy (CDT) and photodynamic therapy (PDT). Importantly, NO and reactive oxygen species (ROS) can generate reactive nitrogen species (RNS), which can result in DNA damage, further improving the therapeutic effect (cell apoptosis rate up to 93.4%). Moreover, the inherent properties of lanthanide ions endow UMNOCC-PEG with upconversion luminescence (UCL), CT and MRI trimodal imaging capability, achieving precise cancer treatment. By taking advantage of these features, the strategy developed here may provide a promising application foreground to conquer malignant tumors.

The development of near-infrared (NIR) laser triggered phototheranostics for multimodal imaging-guided combination therapy is highly desirable. However, multiple laser sources, as well as inadequate therapeutic efficacy, impede the application of phototheranostics. Here, we develop an all-in-one theranostic nanoagent PEGylated DCNP@DMSN-MoO

Reactive oxygen species (ROS)-based therapeutic modalities including chemodynamic therapy (CDT) and photodynamic therapy (PDT) hold great promise for conquering malignant tumors. However, these two methods tend to be restricted by the overexpressed glutathione (GSH) and hypoxia in the tumor microenvironment (TME). Here, we develop biodegradable copper/manganese silicate nanosphere (CMSN)-coated lanthanide-doped nanoparticles (LDNPs) for trimodal imaging-guided CDT/PDT synergistic therapy. The tridoped Yb3+/Er3+/Tm3+ in the ultrasmall core and the optimal Yb3+/Ce3+ doping in the shell enable the ultrabright dual-mode upconversion (UC) and downconversion (DC) emissions of LDNPs under near-infrared (NIR) laser excitation. The luminescence in the second near-infrared (NIR-II, 1000-1700 nm) window offers deep-tissue penetration, high spatial resolution, and reduced autofluorescence when used for optical imaging. Significantly, the CMSNs are capable of relieving the hypoxic TME through decomposing H2O2 to produce O2, which can react with the sample to generate 1O2 upon excitation of UC photons (PDT). The GSH-triggered degradation of CMSNs results in the release of Fenton-like Mn2+ and Cu+ ions for •OH generation (CDT); simultaneously, the released Mn2+ ions couple with NIR-II luminescence imaging, computed tomography (CT) imaging, and magnetic resonance (MR) imaging of LDNPs, performing a TME-amplified trimodal effect. In such a nanomedicine, the TME modulation, bimetallic silicate photosensitizer, Fenton-like nanocatalyst, and NIR-II/MR/CT contrast agent were achieved "one for all", thereby realizing highly efficient tumor theranostics.

The therapeutic effect of traditional chemodynamic therapy (CDT) agents is severely restricted by their weakly acidic pH and glutathione (GSH) overexpression in the tumor microenvironment. Here, fusiform-like copper(II)-based tetrakis(4-carboxy phenyl)porphyrin (TCPP) nanoscale metal-organic frameworks (nMOFs) were designed and constructed for the first time (named PCN-224(Cu)-GOD@MnO2). The coated MnO2 layer can not only avoid conjugation of glucose oxidase (GOD) to damage normal cells but also catalyzes the generation of O2 from H2O2 to enhance the oxidation of glucose (Glu) by GOD, which also provides abundant H2O2 for the subsequent Cu+-based Fenton-like reaction. Meanwhile, the Cu2+ chelated to the TCPP ligand is converted to Cu+ by the excess GSH in the tumor, which reduces the tumor antioxidant activity to improve the CDT effect. Next, the Cu+ reacts with the plentiful H2O2 by enzyme catalysis to produce a toxic hydroxyl radical (•OH), and singlet oxygen (1O2) is synchronously generated from combination with Cu+, O2, and H2O via the Russell mechanism. Furthermore, the nanoplatform can be used for both TCPP-based in vivo fluorescence imaging and Mn2+-induced T1-weighted magnetic resonance imaging. In conclusion, fusiform-like PCN-224(Cu)-GOD@MnO2 nMOFs facilitate the therapeutic efficiency of chemodynamic and starvation therapy via combination with relief hypoxia and GSH depletion after acting as an accurate imaging guide.

Inventing a tumor-responsive theranostic nanoconstruct shows great potential for improving the therapeutic outcome on cancer. Herein, a facile in situ growth strategy based on polyoxometalate (POM) integrated with the mesoporous silica coated upconversion nanoparticles (UCNPs@mSiO2) has been developed. The product was named as USP, and can be triggered by 808 nm light for cancer theranostic. The POM is ultra-sensitive to the intratumoral acidity and reducibility, which enables the photothermal conversion of 808 nm photon for photothermal therapy (PTT). The POM endows the nanostructure highly hydrophilic surface, which is very significant for in vivo application. Need to point out, the photothermal conversion ability of POM enhances the inner temperature of doxorubicin (DOX)-loaded USP (USP-DOX), realizing a bioresponsiveness and NIR photon co-enhanced chemo-photothermal therapy. The POM can also obviate the DOX leakage in normal tissues while accelerate DOX release in tumor tissues under NIR irradiation. Significantly, the POM endows the nanomedicine self-assemble property in acidic tumor microenvironment, which is highly beneficial for enhancing intratumoral accumulation. Highly effective anticancer therapy of the developed USP-DOX has been validated by the in vitro and in vivo assays. The Gd3+/Nd3+/Yb3+/Er3+ co-doped UCNPs ensure the nanosystem MRI/CT/UCL imaging functions, thus achieving the integration of therapy and diagnosis.

A rare-earth-based upconversion nanocrystal that exhibits anti-Stokes nature has attracted worldwide attention due to its unique physical properties. In this work, a novel core–active shell upconversion nanocrystal (NaErF4:Tm@NaGdF4:Yb) which emits super-bright red emission upon 980 nm near-infrared (NIR) laser excitation is presented. The Er3+ ions act as both sensitizers and activators to enable an efficient upconversion process of core nanocrystals. To mitigate the luminescence quenching caused by the energy migration between the Er3+ ions and internal lattice defects, an energy trapping center of Tm3+ was introduced into the core to confine the energy of Er3+ through an energy back transfer (Er3+ → Tm3+ → Er3+) pathway. After that, an active shell of NaGdF4:Yb was grown on the core zone to simultaneously enable the efficient energy transfer from NIR photons to the upconverting zone and suppress the luminescence quenching caused by surface defects and surface associated ligands. It is worth noting that both the Tm3+ and active shell can enhance the red to green (R/G) ratio of the Er3+ emission, thus resulting in an ultra-bright red emission with high purity. The core–active shell nanoparticles possess more intense (∼20 times higher) emission intensity than core–inert shell nanoparticles (NaErF4:Tm@NaGdF4), and their quantum yield reaches as high as 3.71%. This finding paves a convenient way to obtain red-emissive upconversion nanocrystals with high purity for special applications.

The tumor microenvironment (TME) is complex in composition and unique in nature, and is closely related to the growth, invasion and metastasis of tumor cells. Improving and remodeling the TME to return it to a normalized state can fundamentally disrupt the environment and/or nutrient supply on which tumor cells depend. To achieve this goal, based on the unique physicochemical properties and biological effects of CaO2, we designed and constructed a Ca2+ nanogenerator (named as CaO2-Cu/ICG@PCM) that enables H2O2/O2 self-supplementation and GSH depletion. The 808 nm laser induces the heat generation of photosensitizer indocyanine green (ICG) to initiate a series of reactions, followed by the production of copper ions, H2O2, O2 and large amounts of Ca2+, which can eventually lead to the combined treatment of photodynamic therapy (PDT), chemodynamic therapy (CDT) and calcium overload. Additionally, the reaction process is accompanied by the generation of Ca(OH)2, which greatly improves the acidic environment of TME and effectively promotes the oxidation process of GSH by H2O2, achieving the purpose of remodeling TME. It is worth mentioning that a large amount of free Ca2+ accumulating in tumor cells can rapidly initiate the process of calcium overload and calcification, which can not only play a role in tumor suppression, but also assist CT imaging to detect the effect of treatment. Thus, CaO2-Cu/ICG@PCM could be a promising candidate for bioimaging and tumor therapy.

Reducing the scavenging capacity of reactive oxygen species (ROS) and elevating ROS production are two primary goals of developing novel sonosensitizers for sonodynamic therapy (SDT). Hence, ultrathin 2D Bi2 MoO6 -poly(ethylene glycol) nanoribbons (BMO NRs) are designed as piezoelectric sonosensitizers for glutathione (GSH)-enhanced SDT. In cancer cells, BMO NRs can consume endogenous GSH to disrupt redox homeostasis, and the GSH-activated BMO NRs (GBMO) exhibit an oxygen-deficient structure, which can promote the separation of electron-hole pairs, thereby enhancing the efficiency of ROS production in SDT. The ultrathin GBMO NRs are piezoelectric, in which ultrasonic waves introduce mechanical strain to the nanoribbons, resulting in piezoelectric polarization and band tilting, thus accelerating toxic ROS production. The as-synthesized BMO NRs enable excellent computed tomography imaging of tumors and significant tumor suppression in vitro and in vivo. A piezoelectric Bi2 MoO6 sonosensitizer-mediated two-step enhancement SDT process, which is activated by endogenous GSH and amplified by exogenous ultrasound, is proposed. This process not only provides new options for improving SDT but also broadens the application of 2D piezoelectric materials as sonosensitizers in SDT.

Photodynamic therapy (PDT) and photothermal therapy (PTT) combined treatment guided by imaging diagnosis has brought the cancer treatment into a new stage. But simple nanoplatforms with multifunctional therapeutic performance are rarely designed. Herein, we adopt ball-milling method to fabricate spherical BiAgOS nanoparticles as photosensitizer to apply for 808 nm near-infrared (NIR) light triggered PDT and PTT co-therapy. The polyethylene glycol (PEG) modified BiAgOS NPs show a great absorption in the range of visible light to near-infrared region. Under 808 nm laser irradiation, BiAgOS-PEG NPs have obvious photothermal and photosensitive effects together with excellent X-ray computed tomography (CT) imaging function. The in vitro and in vivo experiments exhibit that the BiAgOS-PEG NPs have good biocompatibility, excellent tumor cells inhibition effects simultaneously. Our finding described the first use of BiAgOS-PEG NPs as a semiconductor photosensitizer for anti-cancer treatment, providing a promising strategy to fabricate this kind of material for imaging guided NIR light induced combined tumor treatment.

ZnFe

Synergistic therapy with different treatment mechanisms is an emerging strategy to improve antitumor efficiency. Here, a diversified nanoplatform (Ag2S@MSN-TGF) is synthesized by coating mesoporous silica on Ag2S nanoparticles (NPs), followed by loading hypoxia-active prodrug (tirapazamine) insides the mesoporous silica and coating glucose oxidase (GOx) on the surface. Considering that the degree of hypoxia in tumors is not high enough, GOx is combined with hypoxia-active tirapazamine prodrug, and two important functions are realized. One is the consumption of oxygen to enhance the hypoxic environment and promote the curative effect of tirapazamine, and the other is the consumption of glucose to achieve starvation treatment. Additionally, we take the lead in using Ag2S NPs for second near-infrared (NIR-II, 1064 nm) excited photothermal therapy (PTT). The photothermal conversion efficiency (44.7%) of Ag2S@MSN-TGF is even better than that under 808 nm laser irradiation (38.2%). Finally, in vivo NIR-II fluorescence imaging well demonstrated that Ag2S@MSN-TGF can offer an obvious tracking effect for the therapeutic process. Therefore, superior to any single therapeutic mode, our designed Ag2S@MSN-TGF demonstrates an excellent tumor inhibition effect in vitro and in vivo due to synergistic starvation, hypoxia-active prodrug treatment and PTT effect, suggesting the significant prospect of NIR-II imaging guided antitumor therapy.

Multimodal synergistic therapy based on photodynamic therapy (PDT), photothermal therapy (PTT), and chemodynamic therapy (CDT) has attracted increasing attention in cancer therapy. However, the scant therapeutic efficiency is always a barrier for further application. Herein, a smart tumor microenvironment (TME) responsive nanocatalysts are developed by adopting Fe-Mn layered double hydroxides (FeMn-LDH) as an effective photothermal nanocarrier to load mesoporous silica and chlorin e6 (Ce6)-covalently coated upconversion nanoparticles (UCSP) for multimodal imaging for directed therapy. Under acidic TME, FeMn-LDH degrades into Fe3+ and Mn2+ ions to initiate a Fenton-like reaction inducing CDT and enhancing magnetic resonance imaging. Additionally, Fe3+ can decompose H2 O2 to oxygen (O2 ), enhancing PDT guided by UCSP. As a representative noninvasive imaging probe, the upconversion luminescence will recover after decomposition of FeMn-LDH, and provide high-resolution upconversion luminescent imaging guidance for pinpointed PDT. Moreover, the photothermal properties of FeMn-LDH can further enhance CDT effects. The synergistic therapy and multifunctional imaging can realize the integration of diagnosis and treatment.

Nanocatalytic therapy, using artificial nanoscale enzyme mimics (nanozymes), is an emerging technology for therapeutic treatment of various malignant tumors. However, the relatively deficient catalytic activity of nanozymes in the tumor microenvironment (TME) restrains their biomedical applications. Here, a versatile and bacteria-like PEG/Ce-Bi@DMSN nanozyme is developed by coating uniform Bi2 S3 nanorods (NRs) with dendritic mesoporous silica (Bi2 S3 @DMSN) and then decorating ultrasmall ceria nanozymes into the large mesopores of Bi2 S3 @DMSN. The nanozymes exhibit dual enzyme-mimic catalytic activities (peroxidase-mimic and catalase-mimic) under acidic conditions that can regulate the TME, that is, simultaneously elevate oxidative stress and relieve hypoxia. In addition, the nanozymes can effectively consume the overexpressed glutathione (GSH) through redox reaction. Photothermal therapy (PTT) is introduced to synergistically improve the dual enzyme-mimicking catalytic activities and depletion of the overexpressed GSH in the tumors by photonic hyperthermia. This is achieved by taking advantage of the desirable light absorbance in the second near-infrared (NIR-II) window of the PEG/Ce-Bi@DMSN nanozymes. Subsequently the reactive oxygen species (ROS)-mediated therapeutic efficiency is significantly improved. Therefore, this study provides a proof of concept of hyperthermia-augmented multi-enzymatic activities of nanozymes for tumor ablation.

The strategy of combining imaging and treatment has been shown as a widely studied and promising approach. In this work, we first integrated copper sulfide (CuS) nanoparticles and black phosphorus (BP) nanosheets with strong negative charges via mesoporous silica-coated upconversion nanoparticles (UCNPs). Synergistic treatment of photothermal, photodynamic and chemotherapy can be achieved after loading doxorubicin (DOX). The nanocomposites perform excellent antitumor efficiency under 808 nm near-infrared (NIR) light, and avoid the slightly lower efficiency and limited penetration depth of conventional ultraviolet and visible (UV–vis) light. In this system, the pore size of mesoporous silica and the large specific surface area of BP are advantageous for achieving high DOX loading capacity. Furthermore, the reduction in the red/green (R/G) ratio elicited by DOX release can be employed to determine the extent of DOX release by the fluorescence resonance energy transfer (FRET) process. CT/MR imaging induced by doping of rare earth ions imparts multimode imaging capabilities to nanosystem under 808 nm light irradiation, thereby enabling imaging-guided cancer treatment.

A method of blind signal separation based on second order statistic analytic equations is provided for a single hydrophone. This method takes second order statistics equations as restrictive conditions to construct blind separation criterion, then traditional blind separation methods are used to separate source signals through iterative optimization of genetic algorithm. Simulation demonstrates effectiveness of algorithm and separation performance. Results showed: this method can both separate source signals and estimate parameters such as DOA, intensity. And it not only separate incoherent source signals, but also separate source signals which their frequency spectrum are overlapped each other.