Search

Bi2S3 capsules were developed as an X-ray contrast agent for gastrointestinal motility assessment based on X-ray, CT and spectral CT imaging in vivo. The X-ray attenuation ability of Bi2S3 makes it suitable for gastrointestinal motility evaluation.

IR820, an analog of FDA-approved indocyanine green, is a promising second near-infrared window (NIR-II) fluorescence probe with better NIR-II fluorescence stability and great clinical transformation potential. Moreover, its fluorescence can be further remarkably enhanced by the interaction with albumin. Therefore, it is significant to flexibly design IR820-albumin complex using endogenous or exogenetic albumin to meet the requirements of different biological applications. Herein, we show the rational synthesis of IR820-albumin complex for NIR-II fluorescence imaging-guided surgical treatment of tumors and gastrointestinal obstruction. We compared the NIR-II fluorescence imaging ability of IR820 pre-incubated with albumin or not to visualize tumors and the gastrointestinal tract

The Mn-CDs-based contrast-enhanced magnetic resonance imaging provides a promising method for the non-invasive diagnosis of acute kidney injury, solving the problem of the potential nephrotoxicity of Gd-based contrast agents.

Diverse oxygen generation strategies have been developed to overcome hypoxia in tumors for enhancing the therapeutic efficacy, but inevitably suffering from tedious synthesis process of oxygen generators in vitro before in vivo administration. Herein, we show direct injection of commercially and clinically used KMnO

Clinically used iodinated computer tomography (CT) contrast agents suffer from low sensitivity, and the emerging lanthanide-chelates and CT imaging nanoagents raise great safety concerns. The fusion of high sensitivity and good biocompatibility is highly desired for the development of CT contrast agents. Herein, we propose a facile and green one-pot synthesis strategy for the fabrication of a small molecular CT contrast agent, Bi-diethylene triamine pentaacetate acid (DTPA) complex, for high-performance CT and spectral CT imaging. The Bi-DTPA exhibits yield of near 100%, outstanding water solubility, favorable biocompatibility, large-scale production capability, and superior X-ray attenuation ability, and is successfully applied in high-quality in vivo kidney imaging and gastrointestinal tract CT imaging and appealing spectral CT imaging. The proposed contrast agent can be rapidly excreted from body, avoiding the potential side effects caused by the long-term retention in vivo. Furthermore, our design shows great potential in developing diverse multifunctional contrast agents via chemical modification. The proposed Bi-DTPA with unique superiorities shows a bright prospect in clinic CT imaging, especially spectral CT imaging, and lays down a new way for the design of high-performance CT contrast agents with great clinical transformation potential.

Good biocompatibility, active tumor targeting, and stimulus-responsive release offer great opportunity for precise imaging-guided tumor treatment. However, the current strategies for the fabrication of smart theranostic platforms suffer from tedious synthesis processes. Here, we propose a universal and facile strategy for the fabrication of smart nanoscale metal-organic framework (NMOF)-based nanoplatforms for imaging-guided precise chemotherapy. As a proof of concept, 5-boronobenzene-1,3-dicarboxylic acid (BBDC), as a versatile ligand, was employed for the first time with Gd3+ as metal nodes to prepare a smart magnetic resonance (MR) imaging-guided drug-delivery system. Specific reversible diol-borate condensation enables effortless coating of glucose on the NMOFs to improve their biocompatibility. The specific interaction between glucose and glucose-transported protein ensures active tumor-targeting ability. Moreover, the glucose layer, as a pH-responsive diol-borate gatekeeper, prevents the premature leakage of drugs. The proposed smart theranostic nanoplatform was well used in MR imaging-guided tumor-targeted precise chemotherapy. This strategy is simply extended to the design of other MOF-glucose composites for diverse applications, such as X-ray computed tomography imaging of gastrointestinal tract with Yb-MOFs-Glu. BBDC, as a functional ligand, provides a simple and universal way to fabricate smart NMOF theranostic platforms with multifunction as "three birds with one stone". The facile and universal strategy lays down a new way to develop multifunctional nanoagents for precision medicine.

Surgical adhesives have partly replaced traditional sutures to seal and reattach tissues due to their superiorities in preventing liquids leakage and avoiding secondary damage in the surrounding wound area. Most of the existing adhesives are committed to promoting wound healing and functional recovery. A therapeutic adhesive that assists in clearing the residual tumors in the surgical area is undoubtedly meaningful to obtain a better clinical outcome. Herein, enlightened by commercial BioGlue (albumin/glutaraldehyde sealant), a biocompatible therapeutic albumin/genipin bioglue is designed for postoperative wound adhesion and tumor ablation. The albumin/genipin bioglue is formed by simple mixing of bovine serum albumin (BSA) and genipin (GP) under a 35 °C water bath for 24 h without further purification. The obtained dark-blue fluorescent adhesive exhibits a significant temperature increase accompanied by heating-induced curing once irradiated with an 808-nm laser. This unique characteristic allows BSA-GP a therapeutic adhesive for postoperative wound adhesion and photothermal elimination of residual tumors under laser irradiation. Moreover, its easy injectability and impressive photothermal efficacy also make it feasible for in situ tumor photothermal ablation. The ultrasimple synthetic strategy by mimicking BioGlue endows BSA-GP adhesive with large-scale production capacity and clinical transformation potential, which is a successful paradigm for reforming existing clinical products.

Hemorrhage transformation (HT) is a frequent but maybe fatal complication following acute ischemic stroke due to severe damage of the blood-brain barrier (BBB). Quantitative BBB permeability imaging is a promising method to predict HT in stroke patients for a favorable prognosis. However, clinical gadolinium chelate-based magnetic resonance (MR) imaging of the stroke suffers from a relatively low sensitivity and potential side effects of nephrogenic systemic fibrosis and intracranial gadolinium deposition. Herein, BSA-MnO2 nanoparticles (BM NPs) fabricated by a facile disinfection-mimic method were employed for the permeability imaging of BBB in the stroke for the first time. The BM NPs showed a high T1 relaxivity (r1 = 5.9 mM-1 s-1), remarkable MR imaging ability, and good biocompatibility, allowing the noninvasive timely visualization of BBB permeability in the model rats of middle cerebral artery occlusion (MCAO). Furthermore, increased peak intensity, extended imaging duration, and expanded imaging region indicated by BM NPs in MR imaging showed a good prediction for the onset of HT in MCAO rats. Therefore, BM NPs hold an attractive potential to be an alternative biocompatible MR contrast agent for the noninvasive BBB permeability imaging in vivo, benefiting the fundamental research of diverse neurological disorders and the clinical treatment for stroke patients.

The diagnosis of gastrointestinal (GI) tract diseases is frequently performed in the clinic, so it is crucial to develop high-performance contrast agents for real-time and non-invasive imaging examination of the GI tract. Herein, we show a novel method to synthesize a neodymium (Nd) chelate, Nd-diethylenetriaminepentaacetic acid (Nd-DTPA), on a large scale without byproducts for spectral computed tomography (CT) and second near-infrared window imaging of the GI tract in vivo. The Nd-DTPA was simply generated by heating the mixture of Nd2O3 and DTPA in water at 85 °C for 2 h. This dual-modal imaging agent has the advantages of a simple and green synthesis route, no need of purification process, high yield (86.24%), large-scale production capability (>10 g in lab synthesis), good chemical stability and excellent water solubility (≈2 g mL-1). Moreover, the Nd-DTPA emitted strong near-infrared fluorescence at 1308 nm, and exhibited superior X-ray attenuation ability compared to clinical iohexol. The proposed Nd-DTPA can integrate the complementary merits of dual-modal imaging to realize spatial-temporal and highly sensitive imaging of the GI tract in vivo, and accurate diagnosis of the location of intestinal obstruction and monitor its recovery after surgery. The developed highly efficient method for the gram-scale synthesis of Nd-DTPA and the proposed spectral CT and second near-infrared window dual-modal imaging strategy provide a promising route for accurate visualization of the GI tract in vivo.

Photothermal agents with good biocompatibility, high tumor accumulation efficiency, large-scale production ability, and low cost are crucial for potential photothermal treatment in clinic. Herein, we proposed a green and highly efficient strategy to fabricate a kilogram-scale alginate-Ca2+-Fe powder hydrogel (ALG-Ca2+-Fe) by turning commercial Fe powder into hydrogel for enhanced photothermal therapy. The ALG-Ca2+-Fe was formed by simply dispersing commercial Fe powder into the preformed alginate-Ca2+ hydrogel in a green and energy-/time-saving way. The hydrogel exhibited the advantages of ultrahigh loading capacity of Fe powder (>100 mg mL-1), excellent large-scale production capacity (>1 kg in lab synthesis), low cost (

Photothermal therapy (PTT) with the advantages of high efficiency and minimal invasiveness is a promising technique for tumor therapy, but clinical application of PTT agents has been stifled by the great safety concerns. Herein, a deep blue iodine-starch-alginate (ALG) hydrogel is elegantly fabricated based on the classic and simple "iodine-starch test" for in vivo tumor PTT in a facile and mild way. The iodine-starch-ALG hydrogel composed of clinically used agents is fabricated by dispersing blue iodine-starch complex into alginate-Ca2+ hydrogel, which guarantees the good chemical stability of iodine-starch complex via separating them from surrounding reductive environment. The iodine-starch-ALG hydrogel possesses favorable biocompatibility derived from the biosafe and degradable components and possesses good photothermal heating ability based on iodine-starch chromophore. The proposed iodine-starch-ALG hydrogel is successfully applied in tumor PTT in vitro and in vivo for the first time. This work lays down a novel way for the development of high-performance and biocompatible biomaterials via teaching old drugs new tricks.

Hemorrhage transformation (HT) is a frequent but maybe fatal complication following acute ischemic stroke due to severe damage of the blood-brain barrier (BBB). Quantitative BBB permeability imaging is a promising method to predict HT in stroke patients for a favorable prognosis. However, clinical gadolinium chelate-based magnetic resonance (MR) imaging of the stroke suffers from a relatively low sensitivity and potential side effects of nephrogenic systemic fibrosis and intracranial gadolinium deposition. Herein, BSA-MnO2 nanoparticles (BM NPs) fabricated by a facile disinfection-mimic method were employed for the permeability imaging of BBB in the stroke for the first time. The BM NPs showed a high T1 relaxivity (r1 = 5.9 mM-1 s-1), remarkable MR imaging ability, and good biocompatibility, allowing the noninvasive timely visualization of BBB permeability in the model rats of middle cerebral artery occlusion (MCAO). Furthermore, increased peak intensity, extended imaging duration, and expanded imaging region indicated by BM NPs in MR imaging showed a good prediction for the onset of HT in MCAO rats. Therefore, BM NPs hold an attractive potential to be an alternative biocompatible MR contrast agent for the noninvasive BBB permeability imaging in vivo, benefiting the fundamental research of diverse neurological disorders and the clinical treatment for stroke patients.

Fe–polyphenols coordination polymers have emerged as a versatile theranostic nanoplatform for biological applications owing to the appealing biocompatibility of precursors from nature. Incorporatin...

Multimodal imaging is more suitable for disease diagnosis because of its ability to provide more complementary and accurate information over single-mode imaging. Mn-doped quantum dots (QDs), especially Mn-doped ZnS (ZnSe) QDs, possess unique fluorescent and magnetic properties and are thus attractive for fluorescence/magnetic resonance imaging (MRI) dual-mode imaging. However, the optimal dopant (Mn2+) concentration for maximizing the fluorescence of QDs is relatively low for the MRI imaging. Herein, based on the large Stokes shift of Mn-doped ZnSe QDs, an enrichment strategy with mesoporous silica (MSN) loading was explored for constructing a highly luminescent/paramagnetism Mn-doped ZnSe QDs assembly (MSN@QDs) for improved MRI/optical dual-model imaging. After assembly, the loading density of QDs in MSNs was estimated to be 152 ± 12. Upon loading, the fluorescence of the MSN@QDs assembly was enriched along with QDs (enrichment factor of ∼143). Because of the large Stokes shift (∼200 nm), no appreciable ...

Photothermal therapy with minimal invasiveness and high selectivity has been regarded as a powerful technique for tumor therapy to overcome the risks of toxic side effects and limited therapeutic efficacy of clinic cancer treatments. Among various photothermal therapeutic agents, polypyrrole (PPy) nanoparticles show a promising prospect in tumor ablation in vivo due to their admirable biocompatibility and outstanding photothermal performance. Besides, polypyrrole nanoparticles are extensively applied in biosensors, electrochemical sensors, tissue engineering, flexible microelectronics, and so on. However, the available synthesis methods of PPy nanoparticles are all time-consuming and seriously hindered their highly efficient production for diverse applications. Here we present a microwave-assisted strategy for the fabrication of PPy nanoparticles in 2 min, and the required synthesis time is shortened by 120-720 times compared to that in traditional ways. The prepared PPy nanoparticles possess uniform size, favorable aqueous solubility, and enhanced photothermal performance derived from the stronger near-infrared absorbance. Low cytotoxicity and in vivo toxicity of the nanoparticles were confirmed via comprehensive assessments. The PPy nanoparticle-based photothermal therapy in vitro led to a remarkable death of tumor cells, and in vivo tumor ablation using the nanoparticles was achieved under mild laser irradiation with a FDA-approved safe power. The proposed microwave-assisted synthesis strategy opens up a facile and ultrafast way for the construction of organic nanoparticles and facilitates a wide range of applications of them in biomedicine and other fields.

The minimal invasive percutaneous microwave ablation (MWA) combined with immunotherapy is a promising technique in clinic for the treatment of primary and metastatic tumors. However, elaborate encapsulation carrier designs, complex cellular engineering, and poor applicability are the vexing problems difficult to solve currently. Herein, a general strategy was proposed for the design of an injectable microwave-sensitive immune hydrogel for combined MWA and immunotherapy in vivo for the first time. The mix-and-use hydrogel composed Food and Drug Administration (FDA)-approved components were fabricated by introducing various immunostimulants regardless of hydrophilicity and hydrophobicity into the alginate (ALG)-Ca2+ hydrogel. As a proof of concept, an immunoadjuvant (R837) was employed to synthesize the R837-ALG-hydrogel for systematic studies. This immune hydrogel owns ultra-facile synthesis process, good microwave-sensitivity, adjuvant encapsulation efficiency of nearly 100%, good biocompatibility and syringeability, and large-scale production capability, which could be easily injected into the primary tumor for enhancing MWA. Moreover, the loaded R837 could motivate in situ vaccination by making the utmost of the tumor-associated antigens released after MWA, thereby inducing the robust tumor-specific antitumor immunity to suppress the distant metastatic tumor in vivo. The proposed injectable microwave-sensitive immune hydrogel paves a facile but general avenue with great clinical translation potential for the minimal invasive personalized oncotherapy.

Spectral computed tomography (CT) imaging as a novel imaging technique shows promising prospects in the accurate diagnosis of various diseases. However, clinically iodinated contrast agents suffer from poor signal-to-noise ratio, and emerging heavy-metal-based CT contrast agents arouse great biosafety concern. Herein, we show the fabrication of rhenium sulfide (ReS2) nanoparticles, a clinic radiotherapy sensitizer, as a biosafe spectral CT contrast agent for the gastrointestinal tract imaging and tumor theranostics in vivo by teaching old drugs new tricks. The ReS2 nanoparticles were fabricated in a one-pot facile method at room temperature, and exhibited sub-10 nm size, favorable monodispersity, admirable aqueous solubility, and strong X-ray attenuation capability. More importantly, the proposed nanoparticles possess an outstanding spectral CT imaging ability and undoubted biosafety as a clinic therapeutic agent. Besides, the ReS2 nanoparticles possess appealing photothermal performance due to their intense near-infrared absorption. The proposed nano-agent not only guarantees obvious contrast enhancement in gastrointestinal tract spectral CT imaging in vivo, but also allows effective CT imaging-guided tumor photothermal therapy. The proposed "teaching old drugs new tricks" strategy shortens the time and cuts the cost required for clinical application of nano-agents based on existing clinical toxicology testing and trial results, and lays down a low-cost, time-saving, and energy-saving method for the development of multifunctional nano-agents toward clinical applications.

Bioavailable persistent luminescence material is an ideal internal light source for long-term photodynamic therapy, but inevitably suffers from low utilization efficiency and weak persistent luminescence due to corrosion and screening processes. Herein, we show a facile and smart "turning solid into gel" strategy to fabricate persistent luminescence hydrogel for high-efficient persistent luminescence-sensitized photodynamic therapy. The homogeneous persistent luminescence hydrogel was synthesized via dispersing high-temperature calcined persistent luminescence material without corrosion and screening into a biocompatible alginate-Ca2+ hydrogel. The simple synthesis strategy allows 100% of utilization efficiency and intact persistent luminescence of persistent luminescence material. The persistent luminescence hydrogel possesses favorable biocompatibility, bright persistent luminescence, red light renewability, good syringeability, and strong fixing ability in tumors. The persistent luminescence hydrogel can be easily injected in vivo as a powerful localized light source for superior persistent luminescence-sensitized photodynamic therapy of tumors. The "turning solid into gel" strategy enables taking full advantages of persistent luminescence for biological applications, and shows great potential in utilizing diverse theranostic agents regardless of hydrophilicity and hydrophobicity.

Simplifying synthesis and administration process, improving photothermal agents’ accumulation in tumors, and ensuring excellent biocompatibility and biodegradability are keys to promoting the clinical application of photothermal therapy. However, current photothermal agents have great difficulties in meeting the requirements of clinic drugs from synthesis to administration. Herein, we reported the in situ formation of a Ca2+/Mg2+ stimuli-responsive ICG–alginate hydrogel in vivo for localized tumor photothermal therapy. An ICG–alginate hydrogel can form by the simple introduction of Ca2+/Mg2+ into ICG–alginate solution in vitro, and the widely distributed divalent cations in organization in vivo enabled the in situ fabrication of the ICG–alginate hydrogel without the leakage of any agents by simple injection of ICG–alginate solution into the body of mice. The as-prepared ICG–alginate hydrogel not only owns good photothermal therapy efficacy and excellent biocompatibility but also exhibits strong ICG fixati...

Multifunctional nanoprobes that provide diagnosis and treatment features have attracted great interest in precision medicine. Near-infrared (NIR) persistent luminescence nanoparticles (PLNPs) are optimal materials due to no in situ excitation needed, deep tissue penetration, and high signal-to-noise ratio, while activatable optical probes can further enhance signal-to-noise ratio for the signal turn-on nature. Here, we show the design of an activatable multifunctional PLNP/copper sulfide (CuS)-based nanoprobe for luminescence imaging-guided photothermal therapy in vivo. Matrix metalloproteinases (MMPs)-specific peptide substrate (H2N–GPLGVRGC–SH) was used to connect PLNP and CuS to build a MMP activatable system. The nanoprobe not only possesses ultralow-background for in vivo luminescence imaging due to the absence of autofluorescence and optical activatable nature but also offers effective photothermal therapy from CuS nanoparticles. Further bioconjugation of c(RGDyK) enables the nanoprobe for cancer-ta...

High-performance and biocompatible contrast agents are the key to accurate diagnosis of various diseases in vivo via CT imaging. Fabrication of pure Bi nanoparticles is the best way to maximize X-ray absorption efficiency due to the ultrahigh X-ray attenuation ability of Bi and 100% content of Bi element. However, high-quality Bi nanoparticles prepared through a facile strategy are still lacking. Herein, we report a simple noninjection method to fabricate uniformly sized pure Bi nanoparticles using only two commercial reagents by simply heating the mixture of raw materials in a short time. The obtained Bi nanoparticles owned highly uniform size, excellent monodispersity, and impressive antioxidant capacity. After being modified with oligosaccharide, the "sweet" Bi nanoprobe with comfortable patient experience and favorable biocompatibility was successfully used in CT visualization of gastrointestinal tract in detail.

Metal–organic frameworks (MOFs) have shown great potential in designing theranostic probes for cancer diagnosis and therapy due to their unique properties, including versatile structures and composition, tunable particle and pore size, enormous porosity, high surface area, and intrinsic biodegradability. In this study, we demonstrate novel MOF-based theranostic Fe3O4@UiO-66 core–shell composites constructed by in situ growth of a UiO-66 MOF shell on a Fe3O4 core for simultaneous drug delivery and magnetic resonance (MR) imaging. In the composites, the UiO-66 shell is devoted for encapsulating the drug, whereas the Fe3O4 core serves as a MR contrast agent. The Fe3O4@UiO-66 core–shell composites show good biocompatibility, high drug loading capacity, sustained drug release, and outstanding MR imaging capability, as well as effective chemotherapeutic efficacy, demonstrating the feasibility of designing theranostic Fe3O4@UiO-66 core–shell composites for cancer diagnosis and therapy.

Persistent luminescence nanoparticles (PLNPs) are unique optical materials emitting long-lasting luminescence after ceasing excitation. Such a unique optical feature allows luminescence detection without constant external illumination to avoid the interferences of autofluorescence and scattering light from biological fluids and tissues. Besides, near-infrared (NIR) PLNPs have advantages of deep penetration and the reactivation of the persistent luminescence (PL) by red or NIR light. These features make the application of NIR-emitting PLNPs in long-term bioimaging no longer limited by the lifetime of PL. To take full advantage of PLNPs for biological applications, the versatile strategies for bridging PLNPs and biological system become increasingly significant for the design of PLNPs-based nanoprobes. In this Account, we summarize our systematic achievements in the biological applications of PLNPs from biosensing/bioimaging to theranostics with emphasizing the engineering strategies for fabricating specific PLNPs-based nanoprobes. We take surface engineering and manipulating energy transfer as the major principles to design various PLNPs-based nanoprobes based on the nature of interactions between nanoprobes and targets. We have developed target-induced formation or interruption of fluorescence resonance energy transfer systems for autofluorescence-free biosensing and imaging of cancer biomarkers. We have decorated single or dual targeting ligands on PLNPs for tumor-targeted imaging, and integrated other modal imaging agents into PLNPs for multimodal imaging. We have also employed specific functionalization for various biomedical applications including chemotherapy, photodynamic therapy, photothermal therapy, stem cells tracking and PL imaging-guided gene therapy. Besides, we have modified PLNPs with multiple functional units to achieve challenging metastatic tumor theranostics. The proposed design principle and comprehensive strategies show great potential in guiding the design of PLNPs nanoprobes and promoting further development of PLNPs in the fields of biological science and medicine. We conclude this Account by outlining the future directions to further promote the practical application of PLNPs. The novel protocols for the synthesis of small-size, monodisperse, and water-soluble PLNPs with high NIR PL intensity and superlong afterglow are the vibrant directions for the biomedical applications of PLNPs. In-depth theories and evidence on luminescence mechanism of PLNPs are highly desired for further improvement of their luminescence performance. Furthermore, other irradiations without tissue penetrating depth limit, such as X-ray, are encouraged for use in energy storage and re-excitation of PLNPs, enabling imaging in deep tissue in vivo and integrating other X-ray sensitized theranostic techniques such as computed tomography imaging and radiotherapy. Last but not least, PLNPs-based nanoprobes and the brand new hybrids of PLNPs with other nanomaterials show a bright prospect for accurate diagnosis and efficient treatment of diseases besides tumors.

Photothermal therapy as a physical therapeutic approach has greatly attracted research interest due to its negligible systemic effects. Among the various photothermal agents, CuS nanoparticles have been widely used due to their easy preparation, low cost, high stability and strong absorption in the NIR region. However, the ambiguous biotoxicity of CuS nanoparticles limited their bio-application. So it is highly desirable to develop biocompatible CuS photothermal agents with the potential of clinical translation. Herein, we report a novel method to synthesize biocompatible CuS nanoparticles for photothermal therapy using bovine serum albumin (BSA) as a template via mimicking biomaterialization processes. Owing to the inherent biocompatibility of BSA, the toxicity assays in vitro and in vivo showed that BSA-CuS nanoparticles possessed good biocompatibility. In vitro and in vivo photothermal therapies were performed and good results were obtained. The bulk of the HeLa cells treated with BSA-CuS nanoparticles under laser irradiation (808 nm) were killed, and the tumor tissues of mice were also successfully eliminated without causing any obvious systemic damage. In summary, a novel strategy for the synthesis of CuS nanoparticles was developed using BSA as the template, and the excellent biocompatibility and efficient photothermal therapy effects of BSA-CuS nanoparticles show great potential as an ideal photothermal agent for cancer treatment.

MR contrast agents play a crucial role in the early diagnosis of various diseases, and many nanoprobes with versatile properties have been developed. However, in order to seek high sensitivity, the biocompatibility and systemic toxicity assessment of the nanoprobes have attracted much less attention. To meet clinical requirements, it is highly desirable to develop a highly sensitive and biocompatible nanoprobe using a facile procedure. Herein, we report a sensitive and biocompatible Gd2O3 nanoprobe using hyaluronic acid (HA) via a one-pot facile synthesis. HA not only endows the nanoprobe with excellent biocompatibility, but also gives a synergistic effect for improving the sensitivity of the nanoprobe in the aspects of increasing rotational correlation time, water exchange rate and the ratio of surface Gd3+ to the inner ones. What’s more, the nanoprobe has specific ability for adrenal gland MR imaging. These results suggest that the HA–Gd2O3 nanoprobe has a potentially promising application in MR imaging in vivo.

Clinical diagnosis of malignant tumors using nanoprobes needs severe improvements in the aspects of sensitivity and biocompatibility. Integrating a dual-targeting strategy with the selection of human-inherent elements and molecules as raw materials shows great potential in the development of a biosafe and sensitive nanoplatform. To carry out the proposed design, we constructed a biocompatible, dual-targeting MR imaging nanoprobe, based on Fe3O4 nanoparticles (NPs) co-modified with inherently innoxious hyaluronic acid (HA) and transferrin (Tf). HA was used as both a template and a targeting molecule to form Fe3O4@HA NPs through a one-step co-precipitation method, which were then further modified with Tf to obtain the dual-targeting Fe3O4@HA@Tf NPs at room temperature. The excellent biocompatibility of the nanoprobe was demonstrated via toxicity assays in vitro and in vivo. The desirable dual-targeting ability towards tumor cells was confirmed by a cellular uptake test (Hela cells, overexpressing both CD44 and transferrin receptors), and the developed nanoprobe was successfully applied in tumor-targeted MR imaging in vivo. In summation, we developed a dual-targeting Fe3O4 nanoprobe, following a facile procedure at room temperature. The nanoprobe showed a high targeting ability towards tumor cells and excellent biocompatibility, which showed its great potential to be applied in the clinical diagnosis of tumors.

Current antigen-encapsulated multifunctional nanovaccines for oncotherapy suffer from limited antigen loading efficiency, low yield, tedious manufacture, and systemic toxicity. Here, an antigen-directed strategy for the fabrication of multifunctional nanovaccine with ultrahigh antigen loading efficiency in a facile way for tumor photothermal-immunotherapy is shown. As a proof of concept, a model antigen ovalbumin (OVA) is used as a natural carrier to load a representative theranostic agent indocyanine green (ICG). Mixing OVA and ICG in aqueous solution gives the simplest multifunctional nanovaccine so far. The nanovaccine owns antigen loading efficiency of 80.8%, high yield of >90%, intense near-infrared absorption and fluorescence, excellent reproducibility, good aqueous solubility and stability, and favorable biocompatibility. These merits not only guarantee sensitive labeling/tracking and efficient stimulation of dendritic cells, but also reliable imaging-guided photothermal-immunotherapy of tumors and tumor prevention. The proposed strategy provides a facile and robust method for large-scale and reproducible fabrication of multifunctional nanovaccines with ultrahigh antigen loading efficiency for tumor therapy.

Based on the patient’s CT data, a three-dimensional fracture model was established, meanwhile a solid model of equal proportions with the rapid prototyping machine was built. Depending on completely knowing the condition of damage, surgeons made different operational plans and simulated the reset of the fracture on the solid model. In addition, according to the fixed schemes and positions of resetting simulation, the femoral nails were fixed in Imagware and simulations was done on the loading condition with single leg in Abaqus. By simulating the physical models of fracture resetting, surgical techniques has been improved. Through comparing the simulate results of different types of femoral nails, the reasonable program of implant was determined. The accuracy and validity of the model programs were verified by intraoperative and postoperative follow-up. Thus a more feasible surgical program method was established.

The ability to manipulate the upconversion luminescence of lanthanide-ion doped fluoride upconversion nanoparticles (UCNPs) is critical and highly desired due to their wide applications in color displays, multiplexing bioassays and multicolor imaging. Here, we developed a facile strategy for simultaneously tuning color output and enhancing upconversion emission of Yb3+/Er3+ doped fluoride UCNPs, based on adjusting the crystalline phases and particle size. With the transformation of crystalline phases from α, a transition state of α mixed β, and finally to β phase, the upconversion emission color output changed from red, yellow, and finally turned green. That is, the UCNPs' emission is sensitive to the crystallite size and phase. Moreover, the fluorescence intensity of the obtained UCNPs became stronger with the crystalline phase changing from a to β. Three kinds of UCNPs including α-UCNPs, α mixed β-UCNPs, and β-UCNPs were used for cell imaging, while the transition state phase α mixed β-UCNPs was the better candidate.

To provide the doctors a basis for treating sacral fractures and offer optimal surgical program, three-dimensional (3D) finite element method was used to simulate normal pelvis and the unstable pelvis sufferedIsection, IIsection and III section sacral fracture respectively.The unstable pelvises were respectively fixed with five different internal fixation implants types, which are respectively rectangular plate with cannulated screw, rectangular plate with solid screw, expansile bolt, convex plate with cannulated screw, convex plate with solid screw. The stress distribution and the X, Y, Z direction displacement of the sacrum were calculated for each sacral fracture treatment of five internal fixation implants after giving 500N axial load on lumbar vertebra and were compared with the normal pelvis, then the optimal surgery program were determined. After the analysis, by comparing the five combinations for each sacral fracture treatment of five internal fixation implants, the preferred combinations for the reset treatment of theIsection sacral fractures were rectangular plate with cannulated screw and convex plate with cannulated screw; The preferred combination for the reset treatment of the II section sacral fractures was expansile bolt; The preferred combination for the reset treatment of the III section sacral fractures was convex plate with cannulated screw.

Facile fabrication of multimodal imaging probes is highly desired for bioimaging application due to their integrated advantages of several imaging modalities. Here, we report a simple and one-step mild strategy to fabricate a multifunctional Gd2O3/Au hybrid nanoprobe. Bovine serum albumin (BSA) was used as the template in the biomineralization synthesis. The fabricated BSA-Gd2O3/Au nanoprobe showed excellent chemical stability, intense near-infrared (NIR) fluorescence, and good magnetic resonance imaging (MRI) ability. The multimodal imaging potential of the prepared multifunctional nanoprobe was demonstrated by successful NIR fluorescent and magnetic resonance blood pool imaging. Further modification of BSA-Gd2O3/Au with arginine-glycine-aspartic acid peptide c(RGDyK) (RGD) enabled the nanoprobe for targeted tumor imaging in vivo.

Traditional targeting nanoprobes suffer from the risks of partial loss of targeting activity and nanoparticle aggregation induced by post-synthetic modifications, ambiguous toxicity, tedious synthesis procedures and environmentally hazardous processes. Herein, we report a green and facile strategy to fabricate transferrin-indocyanine green nanoparticles as a smart theranostic agent with intrinsic biosafety and active targeting abilities for near-infrared fluorescent imaging and photothermal therapy of tumors. Simple mixing of transferrin and indocyanine green enables their self-assembly in aqueous solution to form nanoparticles with excellent water solubility, colloidal stability, favorable biocompatibility and impressive active targeting theranostic effects in vitro and in vivo. The transferrin-indocyanine green nanoparticles show great potential in theranostic applications of tumors in clinical therapy.

The versatile application of nanoparticles in integrating imaging and therapy has aroused extensive research interest in precision medicine. Of the various nanoparticles that have been studied, CuS has shown great potential in the construction of multifunctional agents, owing to its excellent photothermal heating properties. Herein, we report a facile one-pot biomineralization approach for the preparation of versatile bovine-serum-albumin-conjugated CuS/Gd2 O3 hybrid nanoparticles (BSA-CuS/Gd2 O3 HNPs), which simultaneously possessed strong longitudinal relaxivity, an outstanding photothermal effect, high drug-loading capacity, and pH/temperature-responsive drug release. The versatile nanoparticles were used for magnetic resonance imaging (MRI) and antitumor photothermal chemotherapy, both in vitro and in vivo. In vivo MRI showed that the BSA-CuS/Gd2 O3 HNPs had a long circulation time and effective passive tumor-uptake ability. More importantly, combined in vitro and in vivo therapy demonstrated that drug-loaded BSA-CuS/Gd2 O3 HNPs offered outstanding synergistic therapeutic efficacy for tumor inhibition.

Versatile bioinspired strategies are urgently needed to fabricate high-performance nanoprobes for biomedical application. Herein, a novel bioinspired technology of mimicking drug–substrate interaction is reported for the fabrication of high-performance nanoprobes. As a proof of concept, a multifunctional bovine serum albumin (BSA)-MnO2 nanoparticle-based nanoplatform is strategically engineered via mimicking the disinfection process of KMnO4 in an extremely facile way. The prepared BSA-MnO2 nanoparticles possess sub-10 nm and uniform size, excellent colloidal stability, and impressive T1 relaxivity of 7.9 mm−1 s−1. The proposed nanoprobe could not only be employed as a high-performance magnetic resonance imaging (MRI) agent for tumor and renal imaging but can also provide a platform for integrating therapeutic strategies toward tumors. The universal strategy could also be easily extended to the fabrication of other nanoprobes for MR imaging in vivo using other bioactive proteins including ovalbumin and transferrin. This work will open a new way for the development of biomaterials in biomedicine applications.

Owing to the biological and clinical significance of deoxyribonuclease I (DNase I), it is highly desirable to develop near-infrared (NIR) fluorescent assays for the determination of DNase I activity. Here we report a label-free NIR fluorescent assay for selective determination of DNase I activity based on malachite green (MG)/G-quadruplexes. In the presence of Na(+) or K(+), single stranded DNA (ssDNA) is able to form a G-quadruplex structure, thus to increase the rigidity of MG structure and result in a remarkable NIR fluorescence. As DNase I is capable of cleaving all types of DNA indiscriminately to release nucleotide products, the G-quadruplexes are cleaved into oligonucleotides in the presence of DNase I. As a result, the rigidity of MG structure is reduced, and the NIR fluorescence of the solution decreases with increase of DNase I activity, providing a useful platform for low-cost, label-free and convenient detection of DNase I activity. Under the optimum conditions, the proposed label-free NIR fluorescent assay gave a detection limit of 1 u mL(-1), and a relative standard deviation of 3.2% for eleven replicate detections of 50 u mL(-1) DNase I. The proposed assay was applied to the determination of DNase I activity in spiked human urine samples with recoveries from 99.1 to 109.0%.