Sensitive detection of matrix metalloproteinase 2 (MMP-2, an important cancer marker associated with tumor invasion and metastasis) activity in vitro and at cellular level is of great significance to clinical diagnosis and medical treatment. With unique physical properties, nanoparticles are emerging as a platform for the construction of conjugates of various biological molecules, which can be expected to generate new types of biosensors. In this work, Fe3O4 NPs were modified with Gd chelates via linking peptides to construct NP–substrate (Fe3O4–pep–Gd) conjugates for kinetic MMP-2 activity assessment in vitro at the cellular level and in vivo. Superparamagnetic Fe3O4 quenched the longitudinal relaxation effect (T1 relaxivity) of the attached Gd chelates by perturbing proton relaxation process under an external magnetic field. MMP-2 cleaved the peptide substrates and released Gd chelates from the local magnetic fields accompanied by T1 relaxivity recovery and T1 contrast enhancement. Benefiting from signal amplification through binding multiple Gd chelates to one linking peptide, Fe3O4–pep–Gd conjugates exhibited high sensitivity for the detection of MMP-2 (as low as 0.5 nM). Enzymatic processes were in good agreement with the integrated Michaelis–Menten model, revealing an unexpected activity enhancement in the initial stage. Fe3O4–pep–Gd conjugates could also probe MMP-2 at cellular level and in vivo that indicates a great promise in in vitro diagnosis (IVD) and disease monitoring.Keywords: enzymatic activity; in vitro diagnosis; in vivo sensing; matrix metalloproteinase; signal amplification; T1 relaxivity recovery;

Manganese-doped magnetite nanoparticles as magnetic resonance imaging (MRI) contrast agents have been well developed in recent years due to their higher saturation magnetization and stronger transverse (T2) contrast ability compared to parent magnetite. However, the underlying role that manganese doping plays in altering the contrast ability of magnetite is still not thoroughly understood. Herein, we investigate the effects of manganese doping on changes of ferrite crystal structures, magnetic properties, and contrast abilities. We developed a successful one-pot synthesis of uniform manganese-doped magnetite (MnxFe3–xO4) nanoparticles with different manganese contents (x = 0–1.06). The saturation magnetization and T2 contrast ability of ferrite nanoparticles increase along with rising manganese proportion, peak when the doping level of MnxFe3–xO4 reaches x = 0.43, and decrease dramatically as the manganese percentage continues to augment. At high manganese doping level, the manganese ferrite nanoparticles may undergo lattice distortion according to analysis of XRD patterns and lattice distances, which may result in low saturation magnetization and eventually low T2 contrast ability. The MnxFe3–xO4 nanoparticles (x = 0.43) with a diameter of ∼18.5 nm exhibit the highest T2 relaxivity of 904.4 mM–1 s–1 at 7.0 T among all the samples and show a much stronger T2 contrast effect for liver imaging than that of other iron oxide contrast agents. These results indicate that the optimized T2 contrast ability of manganese ferrite nanoparticles could be achieved by tuning the manganese doping level. This work also opens a new field of vision for developing high-performance T2 contrast agents by modulating the metal composition of nanoparticles.

There is an urgent demand for the development of new magnetic resonance imaging (MRI) contrast agents (CAs) with high T1 contrast ability and good biocompatibility. Herein, we report a novel albumin-based nanoprobe loaded with ibuprofen-modified gadolinium chelates, named Ibu-Gd–BSA nanoparticles (NPs). The interfacial pore structure among the albumin molecules endows the Ibu-Gd–BSA NPs with geometrical confinement, which could prolong the rotational correlation time (τR) of CAs and the diffusion correlation time (τD) of water molecules trapped within the pores. As a result, the Ibu-Gd–BSA NPs exhibited an extremely high relaxivity of 48.9 mM−1 s−1, which is about 9 times higher than that of the clinical contrast agent Gd-DOTA (Dotarem®). In addition, the Ibu-Gd–BSA NPs showed good biocompatibility in vitro and in vivo due to the intrinsically biocompatible property of each component. Moreover, the Ibu-Gd–BSA NPs showed much longer blood circulation half-life and higher accumulation in tumors due to the enhanced permeability and retention effect compared to small molecular CAs. In vivo T1-weighted MR imaging confirmed that Ibu-Gd–BSA NPs could serve as an optimal candidate for sensitive tumor imaging. This study provides a facile strategy to assemble geometrically confined albumin-based nanoparticles as T1 CAs with high biocompatibility and enhanced contrast ability, which have great potential for diverse uses in biomedical imaging and disease detection.

Magnetic resonance contrast agents with T1–T2 dual mode contrast capability have attracted considerable interest because they offer complementary and synergistic diagnostic information, leading to high imaging sensitivity and accurate diagnosis. Here, we reported a facile strategy to construct albumin based nanoparticles loaded with hydrophobic gadolinium chelates by hydrophobic interaction for magnetic resonance imaging (MRI). We synthesized a glycyrrhetinic acid-containing Gd-DOTA derivative (GGD) and loaded GGD molecules into BSA nanoparticles to form GGD–BSA nanoparticles (GGD–BSA NPs). The large size and porous structure endow GGD–BSA NPs with geometrical confinement, which restricts the tumbling of GGD and the diffusion of surrounding water molecules. As a result, GGD–BSA NPs exhibit ultrahigh T1 and T2 relaxivities, which are approximately 8-fold higher than those of gadolinium-based clinical contrast agents at 0.5 T. Besides, due to the intrinsic properties of their components, GGD–BSA NPs show good biocompatibility in vitro and in vivo, which warrants their great potential in clinical translation. Furthermore, GGD–BSA NPs show remarkable sensitivity in noninvasive detection of liver tumors by self-confirmed T1–T2 dual-mode contrast-enhanced MRI. All of these merits make GGD–BSA NPs a potential candidate for fruitful biomedical and preclinical applications.

The health risk of exposure to manufactured nano- and submicro-materials leads to an increasing effort to explore their biological effects and potential toxicity in detail. Here, we show that silica sub-microspheres (0.1 to 2.1 μm in diameter), the major component of dust or particulate matter less than 2.5 μm (PM 2.5), induce autophagy depending on the levels of cellular endocytosis. Due to the suitable size for cellular endocytosis, 0.5–0.7 μm silica particles induce the highest levels of autophagy among particles from 0.1 to 2.1 μm in diameter. Changes in cellular endocytosis of silica sub-microspheres lead to alteration of autophagy levels. Furthermore, dephosphorylation of FOXO3A and subsequent translocation to the nucleus may be associated with this autophagy process. Our results reveal the manner in which silica sub-microspheres induce autophagy, emphasize the potential risk of endocytosis of fine particles or other non-degradable materials, and suggest a new signaling pathway involved with autophagy induced by sub-micromaterials.

Stimuli-responsive theranostic platforms are highly desirable for efficient cancer treatment because of their improved specificity and sensitivity. In this work, we report a manganese-iron layered double hydroxide (MnFe-LDH) for the first time and demonstrate that it can serve as a pH-responsive nanoplatform for cancer theranostics. The MnFe-LDH can respond to the acidic microenvironment of solid tumors to release paramagnetic Mn2+ and Fe3+ ions, resulting in great enhancement of the T1 MRI contrast of the tumor area. In addition, the layered structure enables MnFe-LDH to effectively deliver chemotherapeutic drugs in a pH-controlled manner, and therefore it can simultaneously inhibit the growth of solid tumors. We believe that this novel MnFe-LDH with pH-responsive property holds great promise in cancer theranostic applications.

Cation exchange is a powerful means to adjust the properties of nanocrystals through composition change with morphology retention. Herein, we demonstrate that cation exchange can engineer the composition of iron oxide nanocrystals to dramatically improve their contrast ability in magnetic resonance imaging (MRI). We successfully construct manganese and zinc engineered iron oxide nanoparticles with diverse shapes (sphere, cube, and octapod) by facile cation exchange reactions. Extended X-ray absorption fine structure (EXAFS) study indicates that Mn2+ and Zn2+ ions are doped into the crystal lattice of ferrite, and more importantly, most of them are distributed in Td sites of ferrite. These engineered shaped-anisotropic iron oxide nanoparticles exhibit both high saturated magnetization and large effective boundary radii, which leads to remarkable transverse relaxivity (r2), for example, 754.2 mM–1 s–1 for zinc engineered octapod iron oxide nanoparticles. These engineered iron oxide nanoparticles, as high-performance T2 contrast agents for in vivo MR imaging, enable sensitive imaging of early hepatic tumors and metastatic hepatic tumors (as small as 0.4 mm), holding great promise for prompt and accurate diagnosis of cancers and metastases.

High-performance magnetic resonance imaging (MRI) contrast agents and novel contrast enhancement strategies are urgently needed for sensitive and accurate diagnosis. Here we report a strategy to construct a new T1 contrast agent based on the Solomon–Bloembergen–Morgan (SBM) theory. We loaded the ultrasmall gadolinium oxide nanoparticles into worm-like interior channels of mesoporous silica nanospheres (Gd2O3@MSN nanocomposites). This unique structure endows the nanocomposites with geometrical confinement, high molecular tumbling time, and a large coordinated number of water molecules, which results in a significant enhancement of the T1 contrast with longitudinal proton relaxivity (r1) as high as 45.08 mM−1 s−1. Such a high r1 value of Gd2O3@MSN, compared to those of ultrasmall Gd2O3 nanoparticles and gadolinium-based clinical contrast agents, is mainly attributed to the strong geometrical confinement effect. This strategy provides new guidance for developing various high-performance T1 contrast agents for sensitive imaging and disease diagnosis.

Arsenic trioxide has achieved great clinical success in the treatment of acute promyelocytic leukemia (APL). However, it is difficult to replicate the success in other cancers, such as solid tumors, in part because of the rapid renal clearance and dose-limiting toxicity. Nanotechnology is expected to overcome these disadvantages through altering its pharmacokinetics and concentrating the drug at the desired sites. Herein, we report a “one-pot” method to develop arsenic-based nanodrugs by in situ coating the as-prepared arsenic nanocomplexes with porous silica shells. This process can be easily reproduced and scaled up because no complicated synthesis and purification steps are involved. This core–shell embedding method endows nanodrugs with high loading capacity (57.9 wt%) and a prolonged pH-responsive releasing profile, which is crucial to increase the drug concentration at tumor sites and improve the drug efficacy. Based on these unique features, the nanodrugs significantly inhibit the growth of solid tumors without adverse side effects. Therefore, we anticipate that the arsenic-based nanodrugs generated by this facile synthetic route may be a powerful and alternative strategy for solid tumor therapy.

Controlled synthesis of monodisperse iron oxide (IO) nanostructures with diverse morphology remains a major challenge. In this work, IO nanostructures with various shapes and surface structures were synthesized by thermal decomposition of iron oleate (FeOL) in the presence of sodium oleate (NaOL). In a mild condition using 1-octadecene (ODE) as solvent, NaOL may preferentially bind to Fe3O4{111} facets and lead to the formation of Fe3O4{111} facet exposed IO plates, truncated octahedrons, and tetrahedrons. While in a high-boiling temperature tri-n-octylamine (TOA) solvent, we obtained Fe3O4{100} facet exposed IO cubes, concaves, multibranches, and assembled structures by varying the molar ratios of NaOL/FeOL. Moreover, we demonstrated that IO nanoparticles (NPs) with metal-exposed surface structures have enhanced T1 relaxation time shortening effects to protons, and IO NPs with anisotropic shapes are superior in protons T2 relaxation shortening due to the larger effective radii compared to that of spherical IO NPs. This study can provide rational design considerations for the syntheses and applications of IO nanostructures for a broad community of material research fields.

Magnetic resonance imaging (MRI) contrast agents with both positive (T1) and negative (T2) contrast abilities are needed in clinical diagnosis for fault-free accurate detection of lesions. We report a facile synthesis of europium-engineered iron oxide (EuIO) nanocubes as T1 and T2 contrast agents for MRI in living subjects. The Eu(III) oxide-embedded iron oxide nanoparticles significantly increase the T1 relaxivity with an enhanced positive contrast effect. EuIO nanocubes with 14 nm in diameter showed a high r1 value of 36.8 mM−1 s−1 with respect to total metal ions (Fe + Eu), which is about 3 times higher than that of Fe3O4 nanoparticles with similar size. Moreover, both r1 and r2 values of EuIO nanocubes can be tuned by varying their sizes and Eu doping ratios. After citrate coating, EuIO nanocubes can provide enhanced T1 and T2 contrast effects in small animals, particularly in the cardiac and liver regions. This work may provide an insightful strategy to design MRI contrast agents with both positive and negative contrast abilities for biomedical applications.

Multifunctional nanostructures with both diagnostic and therapeutic capabilities have attracted considerable attention in biomedical research because they can offer great advantages in disease management and prognosis. In this work, a facile way to transfer the hydrophobic iron oxide (IO) nanoparticles into aqueous media by employing carboxylic graphene oxide (GO-COOH) as the transferring agent has been reported. In this one-step process, IO nanoparticles adhere to GO-COOH and form water-dispersible clusters via hydrophobic interactions between the hydrophobic ligands of IO nanoparticles and the basal plane of GO-COOH. The multiple IO nanoparticles on GO-COOH sheets (IO/GO-COOH) present a significant increase in T2 contrast enhancement. Moreover, the IO/GO-COOH nanoclusters also display a high photothermal conversion efficiency and can effectively inhibit tumor growth through the photothermal effects. It is envisioned that such IO/GO-COOH nanocomposites combining efficient MRI and photothermal therapy hold great promise in theranostic applications.

We report a simple strategy to construct a multiple gadolinium complex decorated fullerene (CGDn) as an enhanced T1 contrast agent. The CGDn exhibits much higher T1 relaxivity (∼49.7 mM−1 s−1) than individual Gd-DOTA, and shows excellent T1 contrast enhancement ability both in vitro and in vivo.

Precise nodal staging is particularly important to guide the treatments and determine the prognosis for cancer patients. However, it is still challenging to noninvasively and precisely detect in-depth tumor metastasis in lymph nodes (LNs) because of the small size and high potential of obtaining pseudopositive results. Herein, we report the rational design of a T1–T2 dual-modal MRI contrast agent for accurate imaging of tumor metastasis in LNs using gadolinium-embedded iron oxide nanoplates (GdIOP). The GdIOP were modulated with suitable size in vivo through surface functionalization by zwitterionic dopamine sulfonate (ZDS) molecules. The efficient uptake of GdIOP@ZDS nanoparticles through drainage effect because of the presence of large amount of macrophages and dendritic cells generates both T1 and T2 contrasts in LNs. In contrast, the low uptake of protein-corona-free GdIOP@ZDS nanoparticles by melanoma B16 tumor cells promises pseudocontrast imaging of potential tumor metastasis in LNs. The combination of T1 and T2 imaging modalities allows self-confirmed detection of a metastatic tumor with about 1.2 mm in the minimal dimension in LNs, which is close to the detection limit of submilimeter level of MRI scans. This study provides an efficient and noninvasive strategy to detect tumor metastasis in LNs with greatly enhanced diagnostic accuracy.Keywords: accuracy; lymph node; protein-corona-free; T1−T2 dual-modal; tumor metastasis

The innovative applications of engineered nanoparticles (NPs) in medicine, such as diagnosis and therapy, have attracted considerable attention. It is highly important to predict the interactions between engineered NPs and the complex biological system as well as the impacts on the subsequent behaviors in living subjects. Herein, we report the use of T1 contrast-enhanced magnetic resonance imaging (MRI) to monitor the in vivo behaviors of NPs in a real-time manner. We chose ultrasmall Pd nanosheets (SPNSs) as the object of NPs because of their promise in theranostics and fitness for diverse surface chemistry. SPNSs were modified with different surface coating ligands (e.g., polyethylene glycol, zwitterionic ligands, polyethylenimine) and functionalized with Gd-chelates to render T1 contrast-enhanced capability. MRI real-time monitoring recorded the location and accumulation of SPNSs in small animals and revealed the prominent roles of surface coating ligands in pharmacokinetics. These results highlighted the significance of selecting proper surface coating for particular biomedical assignment. Moreover, we demonstrated a powerful and noninvasive means to predict and detect the behaviors of NPs in living subjects, which may be helpful for rational design and screening of engineered NPs in biomedical applications.

Nanoparticles are generally dispersed in electrolyte solutions for cell research. They may be aggregated and thus strongly influence the subsequent bio-effects. However, this has been often neglected in nanotoxicity research. In this paper, we selected gold nanoparticles as an example and investigated the role of dispersity in cytotoxicity. Our data indicated that the cytotoxicity of aggregated gold nanoparticles is significantly higher than well-dispersed ones. The dispersity-dependent cytotoxicity may be related to the increase of cellular endocytosis and reactive oxygen species. These results highlighted the importance of the dispersity of nanoparticles in nanotoxicity and nanobiotechnology fields.

Delivery of arsenic trioxide (ATO), a clinical anticancer drug, has drawn much attention to improve its pharmacokinetics and bioavailability for efficient cancer therapy. Real-time and in situ monitoring of ATO behaviors in vivo is highly desirable for efficient tumor treatment. Herein, we report an ATO-based multifunctional drug delivery system that efficiently delivers ATO to treat tumors and allows real-time monitoring of ATO release by activatable T1 imaging. We loaded water-insoluble manganese arsenite complexes, the ATO prodrug, into hollow silica nanoparticles to form a pH-sensitive multifunctional drug delivery system. Acidic stimuli triggered the simultaneous release of manganese ions and ATO, which dramatically increased the T1 signal (bright signal) and enabled real-time visualization and monitoring of ATO release and delivery. Moreover, this smart multifunctional drug delivery system significantly improved ATO efficacy and strongly inhibited the growth of solid tumors without adverse side effects. This strategy has great potential for real-time monitoring of theranostic drug delivery in cancer diagnosis and therapy.Keywords: activatable T1 imaging; arsenic trioxide; cancer diagnosis; cancer therapy; monitoring;

Magnetic resonance angiography using gadolinium-based molecular contrast agents suffers from short diagnostic window, relatively low resolution and risk of toxicity. Taking into account the chemical exchange between metal centers and surrounding protons, magnetic nanoparticles with suitable surface and interfacial features may serve as alternative T1 contrast agents. Herein, we report the engineering on surface structure of iron oxide nanoplates to boost T1 contrast ability through synergistic effects between exposed metal-rich Fe3O4(100) facets and embedded Gd2O3 clusters. The nanoplates show prominent T1 contrast in a wide range of magnetic fields with an ultrahigh r1 value up to 61.5 mM–1 s–1. Moreover, engineering on nanobio interface through zwitterionic molecules adjusts the in vivo behaviors of nanoplates for highly efficient magnetic resonance angiography with steady-state acquisition window, superhigh resolution in vascular details, and low toxicity. This study provides a powerful tool for sophisticated design of MRI contrast agents for diverse use in bioimaging applications.Keywords: blood pool contrast agents; high-performance; interface; MRA; surface structure;

Arsenic trioxide is a clinical drug that can be used to successfully treat acute promyelocytic leukemia. However, its therapeutic effect on solid tumors is limited because of the poor pharmacokinetics and dose-limiting toxicity. Here, we report a facile strategy to achieve high anticancer activity of arsenic trioxide by loading the nanoparticulate prodrug into hollow silica inorganic nanoparticles. Because of the appropriate size, pH sensitivity, and surface targeted modification, this smart nanosized drug system can deliver arsenic trioxide into cancer cells efficiently and exhibits much higher cytotoxicity to a variety of cancer cells than free arsenic trioxide. Moreover, this nanomedicine can further promote the differentiation and inhibit the migration of cancer cells. In vivo results suggest that this drug delivery system can significantly inhibit the growth of solid tumors without adverse side effects. This study highlights a feasible drug delivery strategy to expand the use of arsenic trioxide for the effective treatment of solid tumors.

In this paper, we demonstrate the tunable T1 and T2 contrast abilities of engineered iron oxide nanoparticles with high performance for liver contrast-enhanced magnetic resonance imaging (MRI) in mice. To enhance the diagnostic accuracy of MRI, large numbers of contrast agents with T1 or T2 contrast ability have been widely explored. The comprehensive investigation of high-performance MRI contrast agents with controllable T1 and T2 contrast abilities is of high importance in the field of molecular imaging. In this study, we synthesized uniform manganese-doped iron oxide (MnIO) nanoparticles with controllable size from 5 to 12 nm and comprehensively investigated their MRI contrast abilities. We revealed that the MRI contrast effects of MnIO nanoparticles are highly size-dependent. By controlling the size of MnIO nanoparticles, we can achieve T1-dominated, T2-dominated, and T1–T2 dual-mode MRI contrast agents with much higher contrast enhancement than the corresponding conventional iron oxide nanoparticles.

This paper reports that iron carbide nanoparticles with high air-stability and strong saturation magnetization can serve as effective T2 contrast agents for magnetic resonance imaging. Fe5C2 nanoparticles (∼20 nm in diameter) exhibit strong contrast enhancement with an r2 value of 283.2 mM−1 S−1, which is about twice as high as that of spherical Fe3O4 nanoparticles (∼140.9 mM−1 S−1). In vivo experiments demonstrate that Fe5C2 nanoparticles are able to produce much more significant MRI contrast enhancement than conventional Fe3O4 nanoparticles in living subjects, which holds great promise in biomedical applications.

Iron oxide has been developed as either T1 or T2 magnetic resonance imaging (MRI) contrast agents by controlling the size and composition; however, the underlying mechanism of T1 and T2 contrasts in one iron oxide entity is still not well understood. Herein, we report that freestanding superparamagnetic magnetite nanoplates with (111) exposed facets have significant but interactional T1 and T2 contrast effects. We demonstrate that the main contribution of the T1 contrast of magnetic nanoplates is the chemical exchange on the iron-rich Fe3O4(111) surfaces, whereas the T2 relaxation is dominated by the intrinsic superparamagnetism of the nanoplates with an enhanced perturbation effect. We are able to regulate the balance of T1 and T2 contrasts by controlling structure and surface features, including morphology, exposed facets, and surface coating. This study provides an insightful understanding on the T1 and T2 contrast mechanisms, which is urgently needed to allow more sophisticated design of high-performance MRI contrast agents.Keywords: Fe3O4(111); magnetite nanoplates; morphology; T1 and T2 contrasts

Glutathione (GSH) capped CdTe semiconductor quantum dots (QDs) are applied for detecting mercuric ions (Hg2+) of trace quantity. The synthesis of GSH-capped CdTe (CdTe@GSH) QDs is cost-efficient and straightforward. We observed that Hg2+ can quantitatively quench the fluorescence of CdTe@GSH QDs and further induce the slight redshift of emission peaks due to the quantum confinement effect. Detailed studies by spectroscopy, dynamic light scattering (DLS), and electrospray ionization mass spectrometry (ESI-MS) demonstrated that the competitive Hg2+ binding with GSH makes the surface of CdTe QDs exposed, results in gradual aggregation, and quantitatively changes the photophysical properties of QDs. The whole procedure for detecting Hg2+ by this protocol took less than 10 min. The experimental limit of detection (LOD) of Hg2+ can be as low as 5 nM using CdTe@GSH with a low concentration (0.5 nM) because of the excellent fluorescent properties of QDs. This strategy may become a promising means to simply detect Hg2+ in water with high sensitivity.

We report the design and synthesis of small-sized zwitterion-coated gadolinium-embedded iron oxide (GdIO) nanoparticles, which exhibit a strong T1 contrast effect for tumor imaging through enhanced permeation and retention effect and the ability to clear out of the body in living subjects. The combination of spin-canting effects and the collection of gadolinium species within small-sized GdIO nanoparticles led to a significantly enhanced T1 contrast effect. For example, GdIO nanoparticles with a diameter of ∼4.8 nm exhibited a high r1 relaxivity of 7.85 mM–1·S–1 and a low r2/r1 ratio of 5.24. After being coated with zwitterionic dopamine sulfonate molecules, the 4.8 nm GdIO nanoparticles showed a steady hydrodynamic diameter (∼5.2 nm) in both PBS buffer and fetal bovine serum solution, indicating a low nonspecific protein absorption. This study provides a valuable strategy for the design of highly sensitive iron-oxide-based T1 contrast agents with relatively long circulation half-lives (∼50 min), efficient tumor passive targeting (SKOV3, human ovarian cancer xenograft tumor as a model), and the possibility of rapid renal clearance after tumor imaging.Keywords: renal clearance; T1 contrast agent; tumor imaging; ultrasmall nanoparticle; zwitterionic

We described the smart and targeted magnetic nanocarriers to control the delivery and release of anticancer drug doxorubicin (DOX) in vitro and demonstrated that they can exhibit much higher cytotoxicity to cancer cells than free DOX. The conjugation of targeted magnetite nanoparticles (∼14 nm in diameter) and DOX molecule via acid-labile imine bond endows the nanocarriers with three advanced features: magnetically controllable, specific targeting, and pH-responsive. The cell toxicity assays indicated the pH-sensitive magnetic nanocarriers (IC50 of 0.13 μg mL−1 to HeLa cells) have much higher anticancer activity than free DOX (IC50 of 1.16 μg mL−1 to HeLa cells). Moreover, the magnetically guided delivery of nanocarriers can further improve the drug efficacy (IC50 of ∼0.087 μg mL−1 to HeLa cells). The arginine–glycine–aspartic acid (RGD)-modified magnetic nanocarriers recognized the specific cells effectively (IC50 of 0.93 μg mL−1 to U-87 MG cells) and showed the increased cytotoxicity to cancer cells under external magnetic fields. This intelligent (magnetically guided, molecular targeted, and pH-responsive) drug delivery system has the ability to improve the chemotherapeutic efficacy and reduce the side effects, which has a great potential to become a favorable strategy for delivery of drugs to the desired sites in patients.

We combined silver and iron oxide nanoparticles to make unique Ag@Fe2O3 yolk–shell multifunctional nanoparticles by the Kirkendall effect. After the surface functionalization using glucose, the Ag@Fe2O3–Glu conjugates exhibited both high capture efficiency of bacteria and potent antibacterial activity. The Ag@Fe2O3 yolk–shell nanostructures may offer a unique multifunctional platform for simultaneous rapid detection and capture of bacteria and safe detoxification treatment.

We report a simple strategy to construct a multiple gadolinium complex decorated fullerene (CGDn) as an enhanced T1 contrast agent. The CGDn exhibits much higher T1 relaxivity (∼49.7 mM−1 s−1) than individual Gd-DOTA, and shows excellent T1 contrast enhancement ability both in vitro and in vivo.

Nanoparticles are generally dispersed in electrolyte solutions for cell research. They may be aggregated and thus strongly influence the subsequent bio-effects. However, this has been often neglected in nanotoxicity research. In this paper, we selected gold nanoparticles as an example and investigated the role of dispersity in cytotoxicity. Our data indicated that the cytotoxicity of aggregated gold nanoparticles is significantly higher than well-dispersed ones. The dispersity-dependent cytotoxicity may be related to the increase of cellular endocytosis and reactive oxygen species. These results highlighted the importance of the dispersity of nanoparticles in nanotoxicity and nanobiotechnology fields.

Arsenic trioxide is a clinical drug that can be used to successfully treat acute promyelocytic leukemia. However, its therapeutic effect on solid tumors is limited because of the poor pharmacokinetics and dose-limiting toxicity. Here, we report a facile strategy to achieve high anticancer activity of arsenic trioxide by loading the nanoparticulate prodrug into hollow silica inorganic nanoparticles. Because of the appropriate size, pH sensitivity, and surface targeted modification, this smart nanosized drug system can deliver arsenic trioxide into cancer cells efficiently and exhibits much higher cytotoxicity to a variety of cancer cells than free arsenic trioxide. Moreover, this nanomedicine can further promote the differentiation and inhibit the migration of cancer cells. In vivo results suggest that this drug delivery system can significantly inhibit the growth of solid tumors without adverse side effects. This study highlights a feasible drug delivery strategy to expand the use of arsenic trioxide for the effective treatment of solid tumors.

We described the smart and targeted magnetic nanocarriers to control the delivery and release of anticancer drug doxorubicin (DOX) in vitro and demonstrated that they can exhibit much higher cytotoxicity to cancer cells than free DOX. The conjugation of targeted magnetite nanoparticles (∼14 nm in diameter) and DOX molecule via acid-labile imine bond endows the nanocarriers with three advanced features: magnetically controllable, specific targeting, and pH-responsive. The cell toxicity assays indicated the pH-sensitive magnetic nanocarriers (IC50 of 0.13 μg mL−1 to HeLa cells) have much higher anticancer activity than free DOX (IC50 of 1.16 μg mL−1 to HeLa cells). Moreover, the magnetically guided delivery of nanocarriers can further improve the drug efficacy (IC50 of ∼0.087 μg mL−1 to HeLa cells). The arginine–glycine–aspartic acid (RGD)-modified magnetic nanocarriers recognized the specific cells effectively (IC50 of 0.93 μg mL−1 to U-87 MG cells) and showed the increased cytotoxicity to cancer cells under external magnetic fields. This intelligent (magnetically guided, molecular targeted, and pH-responsive) drug delivery system has the ability to improve the chemotherapeutic efficacy and reduce the side effects, which has a great potential to become a favorable strategy for delivery of drugs to the desired sites in patients.

We combined silver and iron oxide nanoparticles to make unique Ag@Fe2O3 yolk–shell multifunctional nanoparticles by the Kirkendall effect. After the surface functionalization using glucose, the Ag@Fe2O3–Glu conjugates exhibited both high capture efficiency of bacteria and potent antibacterial activity. The Ag@Fe2O3 yolk–shell nanostructures may offer a unique multifunctional platform for simultaneous rapid detection and capture of bacteria and safe detoxification treatment.

Stimuli-responsive theranostic platforms are highly desirable for efficient cancer treatment because of their improved specificity and sensitivity. In this work, we report a manganese-iron layered double hydroxide (MnFe-LDH) for the first time and demonstrate that it can serve as a pH-responsive nanoplatform for cancer theranostics. The MnFe-LDH can respond to the acidic microenvironment of solid tumors to release paramagnetic Mn2+ and Fe3+ ions, resulting in great enhancement of the T1 MRI contrast of the tumor area. In addition, the layered structure enables MnFe-LDH to effectively deliver chemotherapeutic drugs in a pH-controlled manner, and therefore it can simultaneously inhibit the growth of solid tumors. We believe that this novel MnFe-LDH with pH-responsive property holds great promise in cancer theranostic applications.