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With the development of materials science, photodynamic-based treatments have gradually entered clinics. Photodynamic therapy is ideal for cancer treatment due to its non-invasive and spatiotemporal properties and is the first to be widely promoted in clinical practice. However, the shortcomings resulting from the gap between technical and clinical demands, such as phototoxicity, low tissue permeability, and tissue hypoxia, limit its wide applications. This article reviews the available data regarding the pharmacological and clinical factors affecting the efficacy of photodynamic therapy, such as photosensitizers and oxygen supply, disease diagnosis, and other aspects of photodynamic therapy. In addition, the synergistic treatment of photodynamic therapy with surgery and nanotechnology is also discussed, which is expected to provide inspiration for the design of photodynamic therapy strategies.

B-mode ultrasound imaging is a significant anatomic technique in clinic, which can display the anatomic variation in tissues. However, it is difficult to evaluate the functional state of organs and display the physiological information in organisms such as the tumor acidic microenvironment (TME). Herein, inspired by the phenomenon of sonographic acoustic shadow during detecting calculus in clinic, a strategy of self-enhanced acoustic impedance difference is proposed to monitor the acidic TME. BiF

Implant-related infections (IRIs) are a serious complication after orthopedic surgery, especially when a biofilm develops and establishes physical and chemical barriers protecting bacteria from antibiotics and the hosts local immune system. Effectively eliminating biofilms is essential but difficult, as it requires not only breaking the physical barrier but also changing the chemical barrier that induces an immunosuppressive microenvironment. Herein, tailored to a biofilm microenvironment (BME), we proposed a space-selective chemodynamic therapy (CDT) strategy to combat IRIs using metastable CuFe5O8 nanocubes (NCs) as smart Fenton-like reaction catalysts whose activity can be regulated by pH and H2O2 concentration. In the biofilm, extracellular DNA (eDNA) was cleaved by high levels of hydroxyl radicals (•OH) catalyzed by CuFe5O8 NCs, thereby disrupting the rigid biofilm. Outside the biofilm with relatively higher pH and lower H2O2 concentration, lower levels of generated •OH effectively reversed the immunosuppressive microenvironment by inducing pro-inflammatory macrophage polarization. Biofilm fragments and exposed bacteria were then persistently eliminated through the collaboration of pro-inflammatory immunity and •OH. The spatially selective activation of CDT and synergistic immunomodulation exerted excellent effects on the treatment of IRIs in vitro and in vivo. The anti-infection strategy is expected to provide a method to conquer IRIs.

The aggregation of hydrophobic photosensitizers limits the therapeutic effect of photodynamic therapy (PDT). Improving the hydrophilicity of photosensitizers can reduce their aggregation for enhancing PDT. Herein, a nanosystem (TPFcNP) is developed by a hydrophobic photosensitizer 5,10,15,20-tetrakis(4-methacryloyloxyphenyl)porphyrin (TMPP) containing multiple carbon-carbon double bonds and a ferrocene-containing amphiphilic block copolymer (PEG-b-PMAEFc), which catalyzes hydrogen peroxide (H2O2) to produce hydroxyl radicals (•OH) in a tumor microenvironment by the Fenton reaction. The •OH could catalyze the addition reaction between the carbon-carbon double bonds of TMPP and overexpressed water-soluble glutathione (GSH) in tumor cells, which greatly improves the hydrophilicity of photosensitizers and reduces their aggregation. Experiments in vitro and in vivo have proved that this strategy significantly enhances the therapeutic efficacy of PDT. Catalyzing intracellular reactions in situ by making use of the tumor microenvironment will open up a new opportunity to solve the aggregation of materials in the tumor for cancer treatment.

Acidic tumor microenvironments, characterized by weak acidity outside the cell (pH ∼ 6.5–7.0), have been revealed as a potential therapeutic target with specific acid-responsible materials. However, the intracellular pH of tumor cells is still slightly alkaline (pH ∼ 7.2–7.4), which is not conducive for nanomaterials that respond to acid but should destroy intracellular substances. Here, we proposed a new strategy for reconstructing the intracellular pH microenvironment to enhance photodynamic therapy. Nanomaterials (UCNP@ZIF + TPP + PA) were designed with an NaYF4:Yb:Tm (UCNP) inner core coated by a porous zeolitic imidazolate framework (ZIF-8) outside for photoacid (PA) and acid-responsive porphyrin (TPP) co-loading. Upon 980 nm laser irradiation, the emission light of UCNP activates PA for H+ release, which achieves reconstruction of the intracellular pH environment. In this new acid condition, TPP becomes protonated (TPP-H+), which reduces its aggregation by enhancing its water solubility, and in turn increases singlet oxygen (1O2) production for enhanced tumor killing. Both in vitro and in vivo experiments have proved that UCNP@ZIF + TPP + PA could reconstruct the intracellular pH environment and enhance therapeutic effect of photodynamic therapy (PDT). Reconstructing the intracellular pH by using light is of great significance for acid-responsive nanosystems to destroy intracellular substances and treat tumors. The results also signify the use of such acid-responsive materials for several other disease therapies.

Radionuclide therapy is an important form of tumor internal radiation therapy (IRT), but its curative effect is restricted by the low radiation intensity and poor targeting ability of nuclides, which hampers efficient killing of DNA. Moreover, the limited penetration depth and nonuniform dose distribution of rays result in “blind” regions with residual living cancer cells, which increases the risk of tumor metastasis. Herein, we developed a new strategy to tactfully incorporate IRT with immunotherapy to achieve highly efficient synergistic therapy. Specifically, gold nanoparticles (AuNPs) co-modified with radioactive iodine-131 and the twin arginine translocation (TAT) peptide (131I-AuNPs-TAT) were constructed, in which TAT-guided nuclei targeting provided highly concentrated β-rays to the most radiosensitive DNA. Meanwhile, β− electrons dashed on AuNPs with a sudden drop in speed can transform into low-dosage X-ray bremsstrahlung radiation. X-rays have a longer penetration depth than β-rays and are able to induce a strong immune response, thus eliminating the area that is blind to short-range β-rays resulting from the limited dose distribution. This method, named “internal radio-immunity therapy (IRIT)”, is a unique approach that combines IRT with immunotherapy to not only enhance radiotherapeutic efficacy but also broaden the clinical applications of 131I, thereby demonstrating great potential for scientific research and clinical applications.

The tumor microenvironment is a complex milieu where neurons constitute an important non-neoplastic cell type. From "cancer neuroscience," the crosstalk between tumors and neurons favors the rapid growth of both, making the cancer-nerve interaction a reciprocally beneficial process. Thus, cancer-nerve crosstalk may provide new targets for therapeutic intervention against cancer and cancer-related symptoms. We proposed a nerve-cancer crosstalk blocking strategy for metastatic bone cancer pain treatment, achieved by Mg/Al layered-double-hydroxide nanoshells (Mg/Al-LDH) with AZ-23 loaded inside and alendronate decorated outside. The pain-causing H

In high-Z element enhanced radiotherapy strategies, the clinical potential of metal-based nanocomposites is always reduced by the serious side effects of leaked heavy metal ions. In this study, we demonstrate a novel anticancer strategy to realize controllable cytotoxicity of metal elements with the aid of high-energy radiation, based on a design of chelator-modified barium peroxide nanoparticles (GL-BaO2 NPs). Free Ba2+ is a potassium channel inhibitor that inhibits cell proliferation. The chelator modification can strongly bind leaked free Ba2+, thus reducing its unwanted side effects in normal tissues. However, under X-ray radiation in tumor regions, the produced hydroxyl radicals will break the chemical structures of chelators. Consequently, the released Ba2+ can access the membrane without a barrier and contribute to tumor treatment. More importantly, the sensitization of Ba in the lattice of barium peroxide will directly transform peroxide groups into reactive hydroxyl radicals, which further guarantees the decomposition of chelators as well as the efficient killing of cells. This strategy, which we termed ion interference therapy, demonstrates a universal paradigm by employing the biological effects of metal ions in tumor treatment, revealing its industrial potential for radiotherapy enhancement.

The key bottleneck problem of chemodynamic therapy (CDT) is that the efficiency depends heavily on an acidic chemical environment. However, there is a sufficient blood supply on the surface of solid tumours, resulting in neutral-pH surface regions, strongly reducing the effectiveness of CDT. In this study, chelating complex ferrous-cysteine–phosphotungstate nanoparticles (FcPWNPs) are synthesized to serve as new CDT nanoagents that break through the limitation of a neutral pH, ensuring CDT efficiencies at both an acidic and neutral pH. The CDT efficiency is increased by introducing cysteine and phosphotungstate, which form an Fe chelating complex to inhibit the formation of inert Fe(OH)x, and accelerate electron transfer between ferric and ferrous ions, respectively. Due to this ferrous chelating strategy and associated electron transfer property, the FcPWNPs can destroy cancer cells from the neutral-pH tumour surface to the acidic interior, thus realizing a complete CDT cancer therapy.

Intracellular catalytic reactions can tailor tumor cell plasticity toward high-efficiency treatments, but the application is hindered by the low efficiency of intracellular catalysis. Here, a magneto-electronic approach is developed for efficient intracellular catalysis by inducing eddy currents of FePt-FeC heterostructures in mild alternating magnetic fields (frequency of f = 96 kHz and amplitude of B ≤ 70 mT). Finite element simulation shows a high density of induced charges gathering at the interface of FePt-FeC heterostructure in the alternating magnetic field. As a result, the concentration of an essential coenzyme-β-nicotinamide adenine dinucleotide-in cancer cells is significantly reduced by the enhanced catalytic hydrogenation reaction of FePt-FeC heterostructures under alternating magnetic stimulation, leading to over 80% of senescent cancer cells-a vulnerable phenotype that facilitates further treatment. It is further demonstrated that senescent cancer cells can be efficiently killed by the chemodynamic therapy based on the enhanced Fenton-like reaction. By promoting intracellular catalytic reactions in tumors, this approach may enable precise catalytic tumor treatment.

Timely detection of liver fibrosis by X‐ray computed tomography (CT) can prevent its progression to fatal liver diseases. However, it remains quite challenging because conventional CT can only identify the difference in density instead of X‐ray attenuation characteristics. Spectral CT can generate monochromatic imaging to specify X‐ray attenuation characteristics of the scanned matter. Herein, an X‐ray energy‐dependent attenuation strategy originated from bismuth (Bi)‐based nanoprobes (BiF3@PDA@HA) is proposed for the accurate diagnosis of liver fibrosis. Bi element in BiF3@PDA@HA can exhibit characteristic attenuation depending on different levels of X‐ray energy via spectral CT, and that is challenging for conventional CT. In this study, selectively accumulating BiF3@PDA@HA nanoprobes in the hepatic fibrosis areas can significantly elevate CT value for 40 Hounsfield units on 70 keV monochromatic images, successfully differentiating from healthy livers and achieving the diagnosis of liver fibrosis. Furthermore, the enhancement produced by the BiF3@PDA@HA nanoprobes in vivo increases as the monochromatic energy decreases from 70 to 40 keV, optimizing the conspicuity of the diseased areas. As a proof of concept, the strategically designed nanoprobes with energy‐dependent attenuation characteristics not only expand the scope of CT application, but also hold excellent potential for precise imaging‐based disease diagnosis., A strategy of energy‐dependent attenuation based on bismuth (Bi) nanomaterials is proposed. BiF3@PDA@HA nanoprobes accumulated in fibrosis‐afflicted areas can attenuate characteristically depending on monoenergetic X‐ray, further leading to fibrotic livers conspicuous via spectral computed tomography (CT). Yet conventional CT with polyenergetic X‐ray can't distinguish liver fibrosis from healthy liver.

Photothermal therapy (PTT) is an efficient approach for cancer treatment. However, accurately monitoring the spatial distribution of photothermal transducing agents (PTAs) and mapping the real-time temperature change in tumor and peritumoral normal tissue remain a huge challenge. Here, we propose an innovative strategy to integrate T1-MRI for precisely tracking PTAs with magnetic resonance temperature imaging (MRTI) for real-time monitoring temperature change in vivo during PTT. NaBiF4: Gd@PDA@PEG nanomaterials were synthesized with favorable T1-weighted performance to target tumor and localize PTAs. The extremely weak susceptibility (1.04 × 10-6 emu g-1 Oe1-) of NaBiF4: Gd@PDA@PEG interferes with the local phase marginally, which maintains the capability of MRTI to dynamically record real-time temperature change in tumor and peritumoral normal tissue. The time resolution is 19 s per frame, and the detection precision of temperature change is approximately 0.1 K. The approach achieving PTT guided by multimode MRI holds significant potential for the clinical application.

Oxidative damage, which mainly includes cell membrane lipid peroxidation (LPO) and DNA damage, plays a vital role in tumor therapy. Unfortunately, the overproduction of polyamines in tumor tissues inhibits cell membrane LPO and promotes DNA repair, leading to the limited oxidative damage efficacy. Herein, we propose an innovative polyamine-activated carbonyl stress strategy based on the MIL-100 @PAO@PVP (MPP) nanoplatform that successfully overcomes the drawbacks of oxidative damage therapy and achieves excellent chemodynamic therapy (CDT)-induced oxidative damage efficacy. Once endocytozed by tumor cells, the loaded plasma amine oxidase (PAO) on MPP can rapidly deplete polyamines at the tumor site to produce a large amount of highly toxic acrolein and H2O2. The produced H2O2 enhances the MIL-100-driven CDT efficiency to promote cell membrane and DNA damage. Furthermore, the depletion of polyamines further reduces the stability of the cell membrane and DNA. More importantly, the reactive product, acrolein, induces carbonyl stress to further increase DNA damage, inhibit the expression of GPx4 and DNA repair proteins, and significantly enhance CDT-induced oxidative damage. Overall, this strategy not only efficiently overcomes the drawbacks of oxidative damage but also provides a new strategy for tumor treatment.

The specific characteristics of the tumor vascular microenvironment such as microvascular permeability and water diffusion have been demonstrated to play essential roles in the evaluation of infiltration of tumors. However, at present, there are few contrast agents (CAs) for magnetic resonance imaging to enhance the sensitivity for acquiring this vital information. Herein, we develop Gd-doped (CeO2:Gd) nanoparticles as CAs to detect the tumor vascular microenvironment with high sensitivity. The lattice oxygen vacancies on the surface of CeO2:Gd nanoparticles could bind considerable water molecules to improve the r1 value, achieving an excellent dynamic contrast-enhanced perfusion weighted imaging performance for the measurement of microvascular permeability. Diffusion limiting of water molecules by oxygen vacancies of CeO2:Gd nanoparticles further enhances the diffusion-weighted magnetic resonance imaging signal in vitro and in vivo. Excitingly, the strategy is not only essential for obtaining tumor vascular microenvironment information but also offers a way for further research in the design of magnetic resonance CAs.

The current positive computed tomography (CT) contrast agents (PCTCAs) including clinical iodides, present high CT density value (CT‐DV). However, they are incapable for the accurate diagnosis of some diseases with high CT‐DV, such as osteosarcoma. Because bones and PCTCAs around osteosarcoma generate similar X‐ray attenuations. Here, an innovative strategy of negative CT contrast agents (NCTCAs) to reduce the CT‐DV of osteosarcoma is proposed, contributing to accurate detection of osteosarcoma. Hollow mesoporous silica nanoparticles, loading ammonia borane molecules and further modified by polyethylene glycol, are synthesized as NCTCAs for the diagnosis of osteosarcoma. The nanocomposites can produce H2 in situ at osteosarcoma areas by responding to the acidic microenvironment of osteosarcoma, resulting in nearly 20 times reduction of CT density in osteosarcoma. This helps form large CT density contrast between bones and osteosarcoma, and successfully achieves accurate diagnosis of osteosarcoma. Meanwhile, The NCTCAs strategy greatly expands the scope of CT application, and provides profound implications for the precise clinical diagnosis, treatment, and prognosis of diseases., A negative computed tomography (CT) contrast agent based on hollow mesoporous silica nanoparticles@ammonia borane@polyethylene glycol nanocomposite can produce H2 in situ at osteosarcoma areas by responding to the acidic microenvironment of osteosarcoma, and prominently reduce the CT density of osteosarcoma, which can form large CT density difference contrast between bones and osteosarcoma, and further realize accurate diagnosis of malignant osteosarcoma.

X-ray-induced photodynamic therapy (X-PDT) has high depth of penetration and has considerable potential for applications in cancer therapy. Scintillators and heavy metals have been adopted to absorb X-rays and transmit the energy to photosensitizers. However, the low efficiency of converting X-rays to reactive oxygen species (ROS) presents a challenge for the use of X-PDT to cure cancer. In this study, a new method based on LiLuF4:Ce@SiO2@Ag3PO4@Pt(IV) nanoparticles (LAPNP) is presented that could be used to enhance the curative effects of X-PDT. To make full use of the fluorescence produced by nanoscintillators (LiLuF4:Ce), a cisplatin prodrug Pt(IV) was utilized as a sacrificial electron acceptor to increase the yield of hydroxyl radicals (·OH) by increasing the separation of electrons and holes in photosensitizers (Ag3PO4). Additionally, cisplatin is produced upon the acceptance of electrons by Pt(IV) and further enhances the damage caused by ·OH. Via two-step amplification, the potential of LAPNP to enhance the effects of X-PDT has been demonstrated.

Two-photon (TP) absorption nanomaterials are highly desirable for deep-tissue clinical diagnostics and orthotopic disease treatment. Here, a well-designed core/shell nanostructure was successfully synthesized with a ZnTPyP self-assembly nanocrystal (ZSN) inner core coated by a homogeneous TiO2 layer outside (ZSN–TO). The ZSN is a good photosemiconductor, showing both one-photon (OP) and TP absorption properties for red fluorescence emission and electron–hole pair generation; TiO2 with good biocompatibility acts as the electron acceptor, which can transfer photoelectron from ZSN to TiO2 for highly effective electron–hole separation, favoring the production of long-life superoxide anion (O2•–) by electrons and oxygen and strong oxidizing hydroxyl radical (•OH) by holes and surrounding H2O. Once pretreated with ZSN–TO, the simultaneous OP-405 nm or TP-800 nm laser stimulation and fluorescent imaging of reactive oxygen species (ROS) showed dynamical and continuous generation of ROS in HeLa cells, with cytotox...

Photothermal therapy (PTT) has been attracting much attention because of its high efficiency and ease of use. Currently deployed PTT, however, shows two main deficiencies: limited penetration depth and interference from heat shock proteins (HSPs). Here we describe a specific application of a pyroelectric material, specifically SnSe-polyvinylpyrrolidone (SnSe-PVP) nanorods, for tumor photoacoustic imaging and PTT, accompanied by pyroelectric dynamic therapy (PEDT), utilizing near-infrared-II (NIR-II) light as the excitation trigger. Moreover, we used PEDT to generate reactive oxygen species (ROS) from SnSe-PVP nanorods and to have the ROS attack HSPs and cancer cells during heating and cooling. This work revealed a high potential for the application of pyroelectric materials in biomedicine, especially for PTT with PEDT via NIR-II light stimulation.

Bismuth (Bi)‐based nanomaterials can exhibit characteristic attenuation depending on different levels of X‐ray energy, known as “energy‐dependent attenuation”. Liver‐fibrosis‐targeted Bi‐based nanomaterials, BiF(3)@PDA@HA, can exhibit characteristic attenuation on monoenergetic X‐ray, endowing the diagnosis of liver fibrosis via monoenergetic imaging of spectral computed tomography. More details can be found in article number 2002548 by Yan Zhou, Wenbo Bu, Zhenwei Yao and co‐workers. [Image: see text]

Gd3+-based contrast agents (CAs) are the most prevailing and widely used for enhanced magnetic resonance imaging (MRI). Numbers of approaches have been developed to regulate the key parameters in order to obtain high-relaxivity CAs, according to the classic Solomon–Bloembergen–Morgen theory. Herein, a method of controlling oxygen vacancies in inorganic nanosized CAs has been developed for largely accelerated proton relaxation to obtain a high r1 value. Such a strategy is verified on oxygen-deficient PEG-NaxGdWO3 nanorods, which exhibit a remarkable r1 value up to 80 mM–1 s–1 (at 0.7 T) and a high r1 value of 32.1 mM–1 s–1 on a clinical 3.0 T scanner, offering an excellent blood pool MRI performance at a low dose. Meanwhile, free electrons and/or oxygen-vacancy-induced small polarons can endow PEG-NaxGdWO3 nanorods with significant photothermal conversion for MRI-guided photothermal therapy.

A material that rapidly absorbs molecular oxygen (known as an oxygen scavenger or deoxygenation agent (DOA)) has various industrial applications, such as in food preservation, anticorrosion of metal and coal deoxidation. Given that oxygen is vital to cancer growth, to starve tumours through the consumption of intratumoral oxygen is a potentially useful strategy in fighting cancer. Here we show that an injectable polymer-modified magnesium silicide (Mg2Si) nanoparticle can act as a DOA by scavenging oxygen in tumours and form by-products that block tumour capillaries from being reoxygenated. The nanoparticles are prepared by a self-propagating high-temperature synthesis strategy. In the acidic tumour microenvironment, the Mg2Si releases silane, which efficiently reacts with both tissue-dissolved and haemoglobin-bound oxygen to form silicon oxide (SiO2) aggregates. This in situ formation of SiO2 blocks the tumour blood capillaries and prevents tumours from receiving new supplies of oxygen and nutrients.

The conversion of bulk water to confined water in biological tissues has been proposed to benefit the treatments of diseases. However, regulating the states of water in vivo is still a challenge. Herein, we constructed nanocatalysts (BiOCl) containing abundant superficial vacancies to confine water in situ and investigated the potential utilization in cancer radiotherapy. Vacancies absorbed bulk water, transformed its structure and converted it to confined water. Enhanced reactivity of confined water increased the efficiency of water radiolysis and the yield of hydroxyl radicals (·OH) from radiation exposure. The results validated the feasibility of water-confinement-based radiosensitization strategy. These findings not only provide a method of constructing confined water in vivo, but also present the potentials of confined water for biological applications.

Disruption of mitochondrial reactive oxygen species (mitoROS) plays a major role in cancer cell apoptosis. Here, we designed a core/shell-structured mitochondria-targeting upconversion-based nano-photosensitizer (TPP-UC(PS)) with a lanthanide-doped upconversion nanoparticle (UCNP) core coated by a photosensitizer (PS)-incorporated dense silica shell. Following irradiation with external near-infrared laser (NIR), TPP-UC(PS) in mitochondria caused serious mitochondrial matrix swelling for the activated upconversion-based photodynamic therapy (UC-PDT), and the mobilization of cytochrome c (cyt c) was amplified in response to the increased mitoROS. Specifically, this heme-containing cyt c could be monitored by varying TPP-UC(PS)’s upconversion luminescence signal (UCL), which may facilitate the in situ detection of cyt c for apoptosis research. As a proof of concept, our designed TPP-UC(PS) may provide significant opportunities for controlling cancer cell apoptosis under NIR stimulation and for studying apoptosis using the dynamic UCL, which is influenced by local cyt c.

Multimodal magnetic resonance (MR) imaging, including MR angiography (MRA) and MR perfusion (MRP), plays a critical role in the diagnosis and surveillance of acute ischemic stroke. However, these techniques are hindered by the low T1 relaxivity, short circulation time, and high leakage rate from vessels of clinical Magnevist. To address these problems, nontoxic polyethylene glycol (PEG)ylated upconversion nanoprobes (PEG-UCNPs) are synthesized and first adopted for excellent MRA and MRP imaging, featuring high diagnostic sensitivity toward acute ischemic stroke in high-resolution imaging. The investigations show that the agent possesses superior advantages over clinical Magnevist, such as much higher relaxivity, longer circulation time, and lower leakage rate, which guarantee much better imaging efficiency. Remarkably, an extremely small dosage (5 mg Gd kg(-1) ) of PEG-UCNPs provides high-resolution MRA imaging with the vascular system delineated much clearer than the Magnevist with clinical dosage as high as 108 mg Gd kg(-1) . On the other hand, the long circulation time of PEG-UCNPs enables the surveillance of the progression of ischemic stroke using MRA or MRP. Once translated, these PEG-UCNPs are expected to be a promising candidate for substituting the clinical Magnevist in MRA and MRP, which will significantly lengthen the imaging time window and improve the overall diagnostic efficiency.

Following the "detect-to-treat" strategy, by biological engineering, the emerging upconversion nanoparticles (UCNPs) have become one of the most promising inorganic nanomedicines, and their biomedical applications have gradually shifted from multimodal tumor imaging to highly efficient cancer therapy. The past few years have witnessed a three-stage development of UCNP-based nanomedicines. On one hand, UCNPs can optimize each clinical treatment tool (chemotherapy, photodynamic therapy (PDT), radiotherapy (RT)) by controlled drug delivery/release, near-infrared (NIR)-excited deep PDT, and radiosensitization, respectively, all of which contribute greatly to the optimized treatment efficacy along with minimized side effects. On the other hand, several individual treatments can be "smartly" integrated into a single UCNP-based nanotheranostic system for multimodal synergetic therapy, which can further improve the overall therapeutic effectiveness. Especially, UCNPs provide more-effective strategies for overcoming tumor hypoxia, thus leading to an ideal treatment efficacy for complete eradication of solid tumors. Finally, the critical issues regarding the future development of UCNPs are discussed to promote the clinic-translational applications of UCNP-based nanomedicines, as well as realization of our "one drug fits all" dream.

In recent decades, extensive attention has been paid to developing anatomic and functional imaging contrast agents that could provide a wealth of complementary bioimaging information. Among them, dual-mode nanoprobes that combine anatomic magnetic resonance imaging (MRI) with functional fluorescent imaging have been mostly used for separated imaging. However, the lack of a machine for simultaneous dual-mode imaging greatly limits further clinical application. One effective strategy is to rationally design MRI contrast agents that own both anatomic and functional MR imaging capability on a single MRI machine, which is highly attractive but remains a great challenge. Herein, ultrasmall NaGdF4@PLL nanodots (NDs) were developed as a novel class of MR contrast agent, which offers a high longitude relaxivity (6.42 mM(-1) s(-1)) for T1-weighted MRI and an excellent sensitive chemical exchange saturation transfer (CEST) effect for pH mapping (at +3.7 ppm). Further in vivo animal experiments show the feasibility of NaGdF4@PLL NDs as contrast agents for efficient kidney and brain tumor diagnosis and pH mapping, which will undoubtedly enhance the diagnosis accuracy and is beneficial for disease precaution and prognosis. Different from other complex dual-mode nanoprobes, the as-constructed NaGdF4@PLL NDs enable both anatomic and functional imaging on a single MR machine, which is a simple and cost-effective new approach to realize dual-mode MR imaging and holds great potential for future clinical application.

Excess electrons play important roles for the construction of superficial active sites on nanocatalysts. However, providing excess electrons to nanocatalysts in vivo is still a challenge, which limits the applications of nanocatalysts in biomedicine. Herein, auger electrons (AEs) emitted from radionuclide 125 (125I) are used in situ to construct active sites in a nanocatalyst (TiO2) and the application of this method is further extended to cancer catalytic internal radiotherapy (CIRT). The obtained 125I‐TiO2 nanoparticles first construct superficial Ti3+ active sites via the reaction between Ti4+ and AEs. Then Ti3+ stretches and weakens the O—H bond of the absorbed H2O, thus enhancing the radiolysis of H2O molecules and generating hydroxyl radicals (•OH). All in vitro and in vivo results demonstrate a good CIRT performance. These findings will broaden the application of radionuclides and introduce new perspectives to nanomedicine., A simple and highly efficient catalytic internal radiotherapy (CIRT) is developed by 125I‐labeled TiO2 nanoparticles. Auger electrons from 125I react with Ti4+ in TiO2 and construct superficial active sites of Ti3+. The generated Ti3+ decreases the energy barriers of H2O and contributes to the generation of •OH upon γ‐rays irradiation, thus enhancing the antitumor effect of IRT.

Biodegradable nanoprodrugs, inheriting the antitumor effects of chemotherapy drugs and overcoming the inevitable drawback of side effects on normal tissues, hold promise as next-generation cancer therapy candidates. Biodegradable nanoprodrugs of transferrin-modified MgO2 nanosheets are developed to selectively deliver reactive oxygen species to cancer cells for molecular dynamic therapy strategy. The nanosheets favor the acidic and low catalase activity tumor microenvironment to react with proton and release nontoxic Mg2+ . This reaction simultaneously produces abundant H2 O2 to induce cell death and damage the structure of transferrin to release Fe3+ , which will react with H2 O2 to produce highly toxic ·OH to kill tumor cells.

Combination therapy is a promising cancer treatment strategy that is usually based on the utilization of complicated nanostructures with multiple components functioning as photo-thermal energy transducers, photo-sensitizers, or dose intensifiers for photothermal therapy (PTT), photodynamic therapy (PDT), or radiation therapy (RT). In this study, ultrathin tungsten oxide nanowires (W18O49) were synthesized using a solvothermal approach and examined as a multifunctional theranostic nanoplatform. In vitro and in vivo analyses demonstrated that these nanowires could induce extensive heat- and singlet oxygen-mediated damage to cancer cells under 980 nm near infrared (NIR)-laser excitation. They were also shown to function as radiation dose intensifying agents that enhance irradiative energy deposition locally and selectively during radiation therapy. Compared to NIR-induced PTT/PDT and RT alone, W18O49-based synergistic tri-modal therapy eradicated xenograft tumors and no recurrence was observed within a 9-month follow up. Moreover, the strong X-ray attenuation ability of the tungsten element (Z = 74, 4.438 cm2·g–1, 100 KeV) qualified these nanowires as excellent contrast agents in X-ray-based imaging, such as diagnostic computed tomography (CT) and cone-beam CT for image-guided radiation therapy. Toxicity studies demonstrated minimal adverse effects on the hematologic system and major organs of mice within one month. In conclusion, these nanowires have shown significant potential for cancer therapy with inherent image guidance and synergistic effects from phototherapy and radiation therapy, which warrants further investigation.

The early detection and thus treatment of breast cancer bone metastasis remain a big challenge clinically. As the most abundant cells within bone tissue, osteocytes have been found to manipulate the activity of early cancer bone metastasis by its crosstalk with cancer cells and osteoclasts. However, conventional bone-targeting nanomedicine has limited bone-lesion specificity and ignores the vital role of osteocytes during breast cancer bone metastasis. Also, it lacks detailed insight into the therapeutic mechanisms, which hinders the following translational practice. Previously, we have shown that a combination of zoledronic acid (ZA) and plumbagin (PL) synergistically alleviates cancer-induced bone destruction. Herein, we further develop a pH-responsive bone-targeting drug delivery system, i.e., the ZA-anchored bimodal mesoporous slica covered gadolinium(III) upconversion nanoparticles loaded with PL, to detect and treat bone metastasis sensitively and specifically at an early stage. This multifunctional nanosystem can target osteocytes to release PL as controlled by pH, decreasing osteocytic RANKL expression synergistically through the structural simulation of adenosine phosphate, which competitively inhibits the phosphorylation of osteocytic protein kinase-a, cAMP-response element binding protein, extracellular regulated protein kinase, and c-Jun N-terminal kinase. More importantly, by establishing a breast cancer bone metastasis mice model via intracardiac injection, we show that tumoriogenesis and osteoclastogenesis can both be attenuated significantly. We thereby realize the effective theranostics of tiny bone metastasis in breast cancer bone metastasis. Our work highlights the significance of theranostic nanomedicine and osteocyte-targeting therapy in the treatment of early bone metastasis, which could be applied in achieving efficient theranostic effects for other bone diseases.

Several decades of research have identified the specific tumor microenvironment (TME) to develop promising nanotheranostics, such as pH-sensitive imaging, acidity-sensitive starving therapy, and hydrogen peroxide-activated chemotherapy, etc. Herein, a novel TME-mediated nanoplatform employing antiferromagnetic pyrite nanocubes is presented, exploiting the intratumoral, overproduced peroxide for self-enhanced magnetic resonance imaging (MRI) and photothermal therapy (PTT)/chemodynamic therapy (CDT). Through the activation of excessive peroxide in the tumor microenvironment, pyrite can lead to in situ surface oxidation and generate hydroxyl radicals to kill tumor cells (i.e., CDT). The increase of the valence state of surface Fe significantly promotes the performance of MRI accompanied by CDT. Furthermore, the localized heat by photothermal treatment can accelerate the intratumoral Fenton process, enabling a synergetic PTT/CDT. To our best knowledge, this is the first study to use the TME-response valence-variable strategy based on pyrite for developing a synergetic nanotheranostic, which will open up a new dimension for the design of other TME-based anticancer strategies.

Excessive free radicals are noxious for living organisms and lead to cell death. Destruction of malignant cells by reactive free radicals has been widely used in cancer treatment. A key consideration is how to allow targeted free radical attack on cancer cells and avoid unwanted side-effects. Herein, we develop an efficient intracellular free radical generation strategy against cancer cells by delivering active ingredients into cancer cells, where free radicals are selectively generated by a lysosomal bioactivation process. Artesunate (ART), which is non-toxic to normal cells, was chosen as the free radical source and transported into cells with a hollow mesoporous silica-based delivery system (ART@HMS). To selectively activate the ART@HMS inside cancer cells, a high-bioactive Fe/O cluster-mesoporous silica nanosystem (Fe/O-MSN) was elaborately prepared. Under the bioactivation of the lysosome, the low-dose ART@HMS together with biocompatible Fe/O-MSN induced significant intracellular generation of toxic free radicals and efficient death of cancer cells. This selective intracellular free radical generation strategy is encouraging for its development into an effective low-cost cancer therapy.

In the version of this Article originally published, incorrect images were used for columns 4–6 in Fig. 4a. Also, the fluorescent scale of columns 1–3 was inconsistent with the others, and the scale bar was missing. The original and corrected panels of Fig. 4a are shown below. This does not affect the text or the conclusions of the paper.

In the present work, the photocatalytic activity of La 2 Ti 2 O 7 for the photoreduction of Cr(VI) ions in water was investigated. The results indicated that La 2 Ti 2 O 7 is an efficient photocatalyst with 98% of reduction efficiency of Cr(VI) ions after 3 h ultraviolet (UV) irradiation. Meanwhile, the stability of La 2 Ti 2 O 7 in the photocatalysis was investigated by repeatedly performing Cr(VI) photoreducing experiments. It can be found that the photocatalytic activity of La 2 Ti 2 O 7 remained almost unchanged after nine successive cycles, and the reduction ratio of Cr(VI) ions was still up to 50% in the twentieth cycle. Furthermore, for practical purposes, the photocatalytic reduction of Cr(VI) ions was studied as functions of the solution pH, initial Cr(VI) concentration and additional salts.

A facile one-pot synthetic approach, using oleic acid and oleylamine as composite stabilizers combined with high-temperature treatment in 1-octadecene, has been developed for the preparation of monodisperse and uniform lanthanum phosphate and europium-doped lanthanum phosphate nanocrystals. In particular, with the present synthetic approach, the size of the resulting nanocrystals could be tuned precisely and continuously from 3.5 to 6.5 nm by seed-mediated epitaxial growth. The as-obtained uniform nanocrystals with hydrophobic surfaces, which show efficient photoluminescence, could be easily dispersed in nonpolar solvents. More importantly, these nanocrystals can also be easily modified to water-dispersed ones with hydrophilic surfaces for potential use in in vitro imaging in bioanalysis. In addition, a synthetic mechanism for these monodisperse nanocrystals is presented and discussed.

High efficiency green-luminescent LaPO 4 :Ce,Tb hierarchical nanostructures with uniform spindle shape have been successfully constructed by a simple Pluronic P123-assisted hydrothermal approach via self-assembling from single-crystalline nanowires. Their morphologies and structures were examined by scanning and transmission electron microscopy. The resulting uniform spindle-shaped microstructures are composed of several tens of aligned single-crystalline nanowires. The surfactant Pluronic P123 was found to play a crucial role in achieving uniform morphology of the final product as compared with the same material but synthesized without the surfactant Pluronic P123. These LaPO 4 :Ce,Tb spindle-shaped microstructures show efficient photoluminescence which is associated with its surface smoothness, high crystallization and uniform morphologies of the micro-architectures.

In this paper, we report for the first time the successful synthesis of novel uniform La2(MoO4)3 dendritic single-crystalline nanostructures via a surfactant-assisted hydrothermal approach. The dendritic nanostructure is composed of trunks with length of several micrometers and plenty of side branches. Both of the trunks and the branches are composed of nanoflakes with thickness of 30–50 nm. The branches are oriented nearly parallel to each other and form an angle of about 45° to the trunk. The polyethylene glycol (PEG) acts as a morphology-directing agent, and by adjusting the experimental parameters, the microstructure of the processed materials could be further controlled in a certain range. The action mechanism of the surfactant has been proposed. This method is a simple and economical route for nanostructure fabrication and might provide a practical reference to the controlled synthesis of other micro-architectures. In addition, the photoluminescence properties of La2(MoO4)3:Eu dendritic nanostructures were studied.

Highly luminescent LaPO4:Eu3+/LaPO4 one-dimensional (1D) core/shell heterostructures were successfully synthesized by a mild and simple self-aggregation process under refluxing or hydrothermal conditions. The resulting 1D core/shell heterostructures were characterized using a variety of techniques including X-ray diffraction (XRD), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), selected area electron diffraction (SAED), and X-ray photoelectron spectroscopy (XPS) to demonstrate successful coating by the crystalline LaPO4. In addition, a possible formation mechanism for this core/shell heterostructure was proposed. Finally, the photoluminescence property of the LaPO4:Eu3+/LaPO4 1D core/shell heterostructures was investigated in detail, which illustrates that the core/shell heterostructures remarkably increase the luminescence efficiency because the LaPO4 shells effectively eliminate surface trap-states and suppress the energy quenching in the energy-transfer processes.

A new synthetic approach using the Pluronic P123-assisted hydrothermal reaction of lanthanum phosphate and europium-doped lanthanum phosphate has been developed, which results in the formation of uniform spindle-shaped microarchitectures most probably by a self-assembly process. Our results reveal that the obtained spindle-shaped microarchitectures consist of several tens of aligned single-crystalline nanowires with smooth, well-defined facets and highly uniform morphologies. These well-defined spindle-shaped microarchitectures show greatly enhanced photoluminescence in these compounds when compared to their counterparts of disordered arrangements. A possible formation mechanism for these spindle-shaped microarchitectures is presented and discussed.

Uniform three-dimensional La2(MoO4)3 nanostructures with a pompon shape have been successfully constructed by a simple surfactant-free hydrothermal approach via self-assembly from single-crystalline nanoflakes. The formation of the uniform pompon-shaped La2(MoO4)3 microarchitectures is closely related to the presence of a proper amount of ammonium ions, and it is proposed that the pompon-shaped microarchitecture forms through an electrostatic attraction/repulsion effect between the oppositely charged flat surface and the edge of nanoflakes. Without the introduction of ammonium ions, no pompon-shaped microarchitectures can be formed, and while under the presence of excess ammonium ions, the nanoflakes on the micropompons become amorphous, twisted, and rugged. The novel microarchitectures of the product can be successfully modified from spherical to columelliform by using a mixed solvent of water/ethanol. This simple and efficient method may provide a practical reference to the controlled synthesis of other microarchitectures.

In this paper, we report a facile route, the tin vapor treatment method, to prepare tin oxide containing mesoporous silica composites (TOMS), which display room-temperature photoluminescence (RT-PL). Among them, TOMS-1 and TOMS-2 were synthesized from mesoporous silica SBA-15 and KIT-6, respectively. They are composed of amorphous SiO2 and tin oxide species and they display strong emission near ultraviolet (UV) when excited by UV light. By increasing the preparation temperature, their Sn content can be increased and subsequently their photoluminescence (PL) intensities can be greatly enhanced. Besides, their PL properties are revealed to be closely related to 2-fold-coordinated tin oxygen-deficient centers.

A new SnO2/mesoporous silica composite was synthesized by a facile method, ‘tin vapor reduction method’, in which mesoporous silica SBA-15 was treated with tin vapor at temperature above 700 °C under inert atmosphere. This material displays enhanced room-temperature photoluminescence (RT-PL) at increased treatment temperature. It is proved that RT-PL properties of this composite are closely related to twofold-coordinated tin oxygen-deficient centers.

We report here a new route to prepare nanocrystalline β-silicon carbide with high specific surface areas and mesoporosity. The preparation method was via the reaction of ordered mesoporous carbons (OMCs, carbon replicas of MCM-48, SBA-15 and KIT-6) with silicon powder at the temperature of 1200–1300 °C, which is below the melting point of silicon, 1420 °C. The SiC samples were characterized by XRD, SEM, TEM, N2 adsorption and other techniques, which showed that the SiC samples were nanocrystalline and had a high surface area of up to 147 m2 g−1 and a mesoporosity in the range of 5–40 nm. In addition, the silicon vapor infiltration method at a temperature beyond 1420 °C was also brought into comparison.

A facile, surfactant-assisted, hydrothermal approach has been developed to synthesize lanthanide phosphate single-crystalline nanowires/nanorods with smooth surface, uniform diameter, and good crystallinity. The surfactant Pluronic P123 was found to play a crucial role on the uniform morphology of lanthanide phosphate single-crystalline nanowires/nanorods. Photoluminescence spectra of the lanthanide phosphate single-crystalline nanowires/nanorods show that these nanowires/nanorods have strong photoluminescent emissions in the ultraviolet-visible and near-infrared regions. The present work is a preliminary and significant step toward the potential luminescent and catalytic applications of lanthanide compound based one-dimensional nanostructures.

Adoptive T lymphocyte immunotherapy is one of the most promising methods to treat residual lesions after glioma surgery. However, the fate of the adoptively transferred T-cells in vivo is unclear, hampering the understanding of this emerging therapy. Thus, it is highly desirable to develop noninvasive and quantitative in vivo tracking of these T-cells to glioma for better identification of the migratory fate and to provide objective evaluation of outcomes of adoptive T-cell immunotherapy targeting glioma. In this work, ultrasmall T1 MR-based nanoprobes, NaGdF4 -TAT, as molecular probes with high longitudinal relaxivity (8.93 mm-1 s-1 ) are designed. By means of HIV-1 transactivator (TAT) peptides, nearly 95% of the adoptive T-cells are labeled with the NaGdF4 -TAT nanoprobes without any measurable side effects on the labeled T-cells, which is remarkably superior to that of the control fluorescein isothiocyanate-NaGdF4 concerning labeling efficacy. Labeled adoptive T-cell clusters can be sensitively tracked in an orthotopic GL261-glioma model 24 h after intravenous infusion of 107 labeled T-cells by T1 -weighted MR imaging. Both in vitro and in vivo experiments show that the NaGdF4 -TAT nanoprobes labeling of T-cells may be a promising method to track adoptive T-cells to improve our understanding of the pathophysiology in adoptive immunotherapy for gliomas.

Colon cancer (CC) is one of the most common intestinal malignancies and is difficult to detect in its early stage by magnetic resonance imaging (MRI) with currently used contrast agents (CAs). The development of targeted CAs contributes to the early diagnosis of CC and thereby enables early intervention and timely therapy. Considering the outstanding performance of upconversion nanoprobes (UCNPs) in high-performance MR and fluorescence imaging, a new type of nanoprobes with considerably enhanced imaging performance is developed herein. Carcinoembryonic antigen (CEA) antibody is conjugated onto the surface of UCNPs to achieve the targeted imaging of early CC tumors, which overexpress CEA. Both toxicity tests and histological/hematological examinations demonstrate the excellent biocompatibility of these CC-targeting nanoprobes, which possess great potential for clinical application in the early diagnosis of CC.