Degradable mesoporous semimetal antimony nanospheres for near-infrared II multimodal theranostics.

Metallic and semimetallic mesoporous frameworks are of great importance owing to their unique properties and broad applications. However, semimetallic mesoporous structures cannot be obtained by the traditional template-mediated strategies due to the inevitable hydrolytic reaction of semimetal compounds. Therefore, it is yet challenging to fabricate mesoporous semimetal nanostructures, not even mention controlling their pore sizes. Here we develop a facile and robust selective etching route to synthesize monodispersed mesoporous antimony nanospheres (MSbNSs). The pore sizes of MSbNSs are tunable by carefully controlling the partial oxidation of Sb nuclei and the selective etching of the as-formed Sb2O3. MSbNSs show a wide absorption from visible to second near-infrared (NIR-II) region. Moreover, PEGylated MSbNSs are degradable and the degradation mechanism is further explained. The NIR-II photothermal performance of MSbNSs is promising with a high photothermal conversion efficiency of ~44% and intensive NIR-II photoacoustic signal. MSbNSs show potential as multifunctional nanomedicines for NIR-II photoacoustic imaging guided synergistic photothermal/chemo therapy in vivo. Our selective etching process would contribute to the development of various semimetallic mesoporous structures and efficient multimodal nanoplatforms for theranostics.

Nanospheres loaded with curcumin promote gut epithelial motility through F-actin-related migration signaling events.

Curcumin, a hydrophobic polyphenol of turmeric, has a variety of biological functions as an herbal supplement, but its poor gastric absorption rate is one of the major factors limiting its oral bioavailability. In the present study, we investigated the functional role of nanospheres loaded with curcumin (nCur) with regard to the motility of gut epithelial HCT116 cells and enterocyte migration along the crypt-villus axis. nCur significantly increased the motility of HCT116 cells and showed much higher migration efficacy than the curcumin. nCur stimulated the small GTPases Rac1 and the phosphorylation of protein kinase C, responsible for the distinctive activation of the mitogen-activated protein kinases. Interestingly, nCur significantly induced the expression of α-actinin, profilin-1, and filamentous (F)-actin as regulated by the phosphorylation of nuclear factor-kappa B during its promotion of cell migration. In mouse models of gut epithelial migration, treatment with nCur had an enhancing effect on the movement of enterocytes along the crypt-villus axis and the expression of cytoskeletal reorganization-related factors. These results indicate that nCur is a functional agent that promotes gut epithelial motility through F-actin-related migration signaling events.

The Pimpled Gold Nanosphere: A Superior Candidate for Plasmonic Photothermal Therapy.

BACKGROUND: The development of highly efficient nanoparticles to convert light to heat for anti-cancer applications is quite a challenging field of research. METHODS: In this study, we synthesized unique pimpled gold nanospheres (PGNSs) for plasmonic photothermal therapy (PPTT). The light-to-heat conversion capability of PGNSs and PPTT damage at the cellular level were investigated using a tissue phantom model. The ability of PGNSs to induce robust cellular damage was studied during cytotoxicity tests on colorectal adenocarcinoma (DLD-1) and fibroblast cell lines. Further, a numerical model of plasmonic (COMSOL Multiphysics) properties was used with the PPTT experimental assays. RESULTS: A low cytotoxic effect of thiolated polyethylene glycol (SH-PEG400-SH-) was observed which improved the biocompatibility of PGNSs to maintain 89.4% cell viability during cytometry assays (in terms of fibroblast cells for 24 hrs at a concentration of 300 µg/mL). The heat generated from the nanoparticle-mediated phantom models resulted in ΔT=30°C, ΔT=23.1°C and ΔT=21°C for the PGNSs, AuNRs, and AuNPs, respectively (at a 300 µg/mL concentration and for 325 sec). For the in vitro assays of PPTT on cancer cells, the PGNS group induced a 68.78% lethality (apoptosis) on DLD-1 cells. Fluorescence microscopy results showed the destruction of cell membranes and nuclei for the PPTT group. Experiments further revealed a penetration depth of sufficient PPTT damage in a physical tumor model after hematoxylin and eosin (H&E) staining through pathological studies (at depths of 2, 3 and 4 cm). Severe structural damages were observed in the tissue model through an 808-nm laser exposed to the PGNSs. CONCLUSION: Collectively, such results show much promise for the use of the present PGNSs and photothermal therapy for numerous anti-cancer applications.

Nanosphere Loaded with Curcumin Inhibits the Gastrointestinal Cell Death Signaling Pathway Induced by the Foodborne Pathogen Vibrio vulnificus.

Curcumin, a hydrophobic polyphenol of turmeric, has a variety of biological functions as a herbal supplement, but its poor gastric absorption rate is one of the major factors limiting its oral bioavailability. In the present study, we have investigated the functional role of a nanosphere loaded with curcumin (CN) during host cell death elicited by the Gram-negative bacterium V. vulnificus in human gastrointestinal epithelial HT-29 cells and an ileal-ligated mouse model. The recombinant protein (r) VvhA produced by V. vulnificus significantly reduced the viability of HT-29 cells. The cytotoxic effect of rVvhA was restored upon a treatment with CN (100 ng/mL), which had shown 1000-fold higher anti-apoptotic efficacy than curcumin. CN inhibited the phosphorylation of c-Src and PKC mediated by intracellular ROS responsible for the distinctive activation of the MAPKs in rVvhA-treated HT-29 cells. Interestingly, CN significantly restored the expression of Bax, Bcl-2, and cleaved caspase-3 as regulated by the phosphorylation of NF-κB. In mouse models of V. vulnificus infection, treatment with CN had a blocking effect that elevated the levels of TUNEL-positive DNA fragmentation and apoptosis-related proteins. These results indicate that CN is a functional agent that manipulates the V. vulnificus VvhA signaling pathway responsible for gastrointestinal cell death.

Hollow mesoporous carbon nanospheres for imaging-guided light-activated synergistic thermo-chemotherapy.

Carbon-based light-activated materials can absorb optical energy to generate photoacoustic (PA) signals for imaging or transduce optical photons to thermal energy, which holds great promise for biomedical applications. Herein, we synthesize hollow and mesoporous carbon nanospheres (HMCNs) with uniform size on a large scale. The properties of hollow cavity and mesoporous structures make the HMCNs achieve high drug loading (480 mg DOX per g HMCNs). The present intense near infrared (NIR) absorbance achieves excellent photoacoustic imaging ability and photothermal conversion efficacy (32.0%). More interestingly, the encapsulated drugs can have a triggered release under NIR irradiation. The investigations in vitro and in vivo demonstrate that HMCNs have excellent biocompatibility, and accumulate in tumors by the enhanced permeability and retention (EPR) effect. Moreover, under NIR irradiation, in vivo evaluation shows that HMCNs can perform strong PA imaging, and induce great tumor inhibition by the combination of chemotherapy and PTT under the guidance of photoacoustic imaging. The present study provides new insight for design of novel biocompatible light-activated carbons for cancer nanotheranostics.

Porous Se@SiO2 nanospheres attenuate cisplatin-induced acute kidney injury via activation of Sirt1.

Cisplatin (CDDP) is the most commonly used chemotherapeutic drug and has an irreplaceable role in cancer treatment. However, CDDP-induced acute kidney injury (AKI) greatly limits its use. Abundant evidence has confirmed that apoptosis contributes to AKI caused by CDDP administration. The nanoparticle form of selenium, also known as Se@SiO2 nanocomposites (NPs), has been proven to be a potential agent to prevent apoptotic cell death. In this article, we established acute kidney injury models in vivo via a single injection of CDDP and used human kidney 2 (HK-2) cells for experiments in vitro. We demonstrated that NPs can improve CDDP-induced renal dysfunction. In addition, therapy with NPs attenuated apoptosis in cells and kidney tissues treated with CDDP. In terms of mechanism, we discovered that Sirt1, a deacetylase with an important role in CDDP-induced acute kidney injury, was remarkedly increased after NPs pretreatment, and the anti-apoptotic effect of the NPs was markedly abrogated after the inhibition of Sirt1. The results linked the protective effect of NPs on nephrotoxicity with Sirt1, suggesting the potential clinical importance of nanomaterials in alleviating the side effects of chemotherapy.

Double Switch Biodegradable Porous Hollow Trinickel Monophosphide Nanospheres for Multimodal Imaging Guided Photothermal Therapy.

Due to the limitation of inorganic nanomaterials in present clinical applications induced by their inherent nonbiodegradability and latent long-term side effects, we successfully prepared double switch degradable and clearable trinickel monophosphide porous hollow nanospheres (NiP PHNPs) modified with bovine serum albumin (BSA). Attributed to their acidic and oxidative double switch degradation capacities, NiP PHNPs can be effectively excreted from mice without long-term toxicity. Moreover, because of the paramagnetic and high molar extinction coefficient property resulting from the strong absorption in the second near-infrared light (NIR II) biowindow, NiP PHNPs have potential to be used for photoacoustic imaging (PAI) and T1-weighted magnetic resonance imaging (MRI) guided photothermal ablation of tumors in the NIR II biowindow. Specifically, it is interesting that the hollow structure and acidic degradation property enable NiP PHNPs to act as intelligent drug carriers with an on-demand release ability. These findings highlight the great potential of NiP PHNPs in the cancer theranostics field and inspire us to further broaden the bioapplications of transition metal phosphides.

Near-infrared light-mediated and nitric oxide-supplied nanospheres for enhanced synergistic thermo-chemotherapy.

Synergistic thermo-chemotherapy based multiple stimuli-responsive drug delivery systems have achieved significant improvement of cancer curative effects compared with single modality treatment. Nevertheless, the efficacy of thermo-chemotherapy is often reduced in drug-resistant tumors and the therapy method is unexpectedly associated with potential toxicity by utilizing poorly degradable materials. Here, we report a simple approach to encapsulate three drug payloads into multi-sensitive and degradable nanospheres (SDC@NS) to achieve anticancer effects. SDC@NS comprise a photothermal agent (cypate), an anticancer agent (doxorubicin), and a nitric oxide donor (SNAP) to achieve controllable drugs release in high concentration glutathione or under near-infrared light (NIR) irradiation. Hyperthermia from NIR-mediated cypate can accelerate cancer cell apoptosis in vitro and tumor tissue ablation in vivo. Furthermore, our results also confirmed that the nitric oxide-based SDC@NS showed significant cytotoxicity compared to the nitric oxide absent group (denoted as DC@NS) and an enhanced chemotherapy effect in vivo. The photothermal effect and payloads can synchronously realize cancer therapy and provide a new insight into the enhanced synergistic therapeutic effect.

Mesoporous NiS2 nanospheres as a hydrophobic anticancer drug delivery vehicle for synergistic photothermal-chemotherapy.

To overcome the unfavorable effects of the hydrophobicity of drugs and cancer resistance, mesoporous NiS2 nanospheres (mNiS2 NSs) have been successfully developed here to package hydrophobic camptothecin (CPT) and realize the synergistic photothermal-chemotherapy of cancer. The mNiS2 NSs which were prepared through a facile solvothermal method here exhibited not only considerable near-infrared (NIR) absorption and good photothermal conversion efficiency as high as 44.6%, but also achieved a NIR light induced CPT release property which were both beneficial for improving the cancer cell-killing efficacy. After a short period of NIR light illumination, a significant intensified cell killing efficacy was observed when 4T1 or HepG2 cancer cells were incubated with CPT@mNiS2 NSs. Thus, mNiS2 NSs have been demonstrated here to have potential as a novel NIR light-responsive hydrophobic drug delivery nanoplatform for realizing synergistic cancer treatment.

Hollow carbon nanospheres derived from biomass by-product okara for imaging-guided photothermal therapy of cancers.

Okara is a by-product of tofu manufacturing and is usually used as a feedstuff. Herein, we developed a methodology of using okara as a carbon source for the preparation of photothermal nano-materials. It's interesting to find that just after calcination, the carbonized okara forms sphere-shaped hollow particles (denoted as HCNS) with an average diameter of 200 nm. Owning to the existence of a cavity, the HCNS was found to exhibit not only a good photothermal conversion efficiency, but also an ideal photoacoustic imaging property, which makes it a promising agent for imaging-guided photothermal therapy (PTT). The high photothermal conversion efficiency can result from the high carbon content and its hollow morphology. The in vitro and in vivo results both demonstrated the biocompatibility and capacity of the plant source carbon spheres for NIR-triggered cancer treatment. Therefore, the current work suggests a new method to gain a safe and low-cost photothermal platform which could be further exploited in biomedical fields.

Combination-Responsive MoO3- x-Hybridized Hyaluronic Acid Hollow Nanospheres for Cancer Phototheranostics.

It is of extreme importance to reduce side effects resulting from the nonspecific uptake of phototherapeutic agents by normal tissues. Currently, the single responsive strategy still cannot entirely satisfy the requirements of practical applications. In this study, we developed one kind of combination-responsive phototherapeutic nanoplatforms, where oxygen-deficient molybdenum oxide (MoO3- x) hybridized hyaluronic acid (HA) hollow nanospheres, namely, MoO3- x@HA HNSs, were constructed via a facile one-step method. In MoO3- x@HA HNSs, the reasonable combination of actively targeted specificity endowed by the HA component and tumor microenvironment-responsive phototherapy activity induced by the MoO3- x component can effectively improve the precision of phototherapy. The in vitro and in vivo experimental results confirm that MoO3- x@HA HNSs can selectively kill CD44-overexpressing cancer cells and inhibit tumor growth under an 808 nm laser irradiation, revealing their remarkable synergistic photothermal therapy/photodynamic therapy effect with CD44 receptor-targeted specificity and pH responsiveness in treating cancer. We also prove that MoO3- x@HA HNSs can serve as one kind of contrast agent to achieve the computed tomography/photoacoustic imaging. Encouraged by these results, it is anticipated that the reasonable combination of active targeting and tumor microenvironment responsiveness can be a promising strategy to develop phototherapeutic nanoplatforms for precise multimodality cancer theranostics.

Bottom-up synthesis of MoS2 nanospheres for photothermal treatment of tumors.

Photothermal therapy (PTT) is providing new opportunities for killing cancer cells. In this work, we introduce a new nanomedicine based on spherical MoS2 nanoparticles for PTT treatment of tumors, prepared using "green" bottom-up technology. To increase water solubility and avoid rapid clearance by the reticuloendothelial system, polyethylene glycol (PEG) was used to coat them. These MoS2-PEG nanospheres with an appropriate size (∼100 nm) exhibit high photothermal conversion efficiency (26.7%). In vitro cellular studies revealed that the MoS2-PEG nanospheres showed negligible cytotoxicity. Additionally, through combining the MoS2-PEG nanosphere samples with NIR irradiation at 808 nm, excellent in vitro tumor cell killing efficacy was achieved. In the 4T1 tumor model, the MoS2-PEG nanospheres exhibited good antitumor efficiency in vivo, displaying complete tumor inhibition over 16 days after treatment. Therefore, MoS2-PEG nanospheres played an important role in tumor destruction, and this concept for developing spherical MoS2-based nanomedicines can serve as a platform technology for the next generation of in vivo PTT agents.

Photothermal combined gene therapy achieved by polyethyleneimine-grafted oxidized mesoporous carbon nanospheres.

Combining controllable photothermal therapy and efficacious gene therapy in a single platform holds great promise in cancer therapy due to the enhanced combined therapeutic effects. Herein, polyethyleneimine-grafted oxidized mesoporous carbon nanospheres (OP) were developed for combined photothermal combined gene therapy in vitro and in vivo. The synthesized OP was characterized to have three dimensional spherical structure with uniformed diameter, ordered mesopores with graphitic domains, high water dispersion with zeta potential of +22 mV, and good biocompatibility. Consequently, OP was exploited as the photothermal convertor with strong NIR absorption and the gene vector via electrostatic interaction, which therefore cannot only deliver the therapeutic gene (pING4) to tumors for gene therapy, but also can eliminate the tumors by photothermal ablation. Moreover, the improved gene therapy accompanied by the NIR photothermally enhanced gene release was also well achieved based on OP. The excellent combined therapeutic effects demonstrated in vitro and in vivo suggested the OP's potential for cancer therapy.

Glucose-Derived Carbonaceous Nanospheres for Photoacoustic Imaging and Photothermal Therapy.

Carbon nanomaterials with small size and unique optical properties have attracted intensive interest for their promising biomedical applications. In this work, glucose-derived carbonaceous nanospheres (CNSs) with high photothermal conversion efficiency up to 35.1% are explored for the first time as a novel carbon-based theranostic agent. Different from most other carbon nanomaterials, the obtained CNSs are highly biocompatible and nontoxic because of their intrinsic hydrophilic property and the use of glucose as raw materials. Under near-infrared laser irradiation (808 nm, 6 W cm(-2)) for 10 min, less than 15% of PC-3M-IE8 cells exposed to CNSs aqueous dispersions (0.16 mg/mL) remained alive. After intravenous administration of CNSs aqueous dispersions into nude mice, the photoacoustic intensity of the tumor region is about 2.5 times higher than that of preinjection. These results indicate that CNSs are suitable for simultaneous photoacoustic imaging and photothermal ablation of cancer cells and can serve as promising biocompatible carbon-based agents for further clinical trials.

Multifunctional magnetic-hollow gold nanospheres for bimodal cancer cell imaging and photothermal therapy.

Multifunctional nanocomposites combining imaging and therapeutic functions have great potential for cancer diagnosis and therapy. In this work, we developed a novel theranostic agent based on hollow gold nanospheres (HGNs) and superparamagnetic iron oxide nanoparticles (SPIO). Taking advantage of the excellent magnetic properties of SPIO and strong near-infrared (NIR) absorption property of HGNs, such nanocomposites were applied to targeted magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) of cancer cells. In vitro results demonstrated they displayed significant contrast enhancement for T2-weighted MRI and strong PAI signal enhancement. Simultaneously, the nanocomposites exhibited a high photothermal effect under the irradiation of the near-infrared laser and can be used as efficient photothermal therapy (PTT) agents for selective killing of cancer cells. All these results indicated that such nanocomposites combined with MRI-PAI and PTT functionality can have great potential for effective cancer diagnosis and therapy.

Anti-TROP2 conjugated hollow gold nanospheres as a novel nanostructure for targeted photothermal destruction of cervical cancer cells.

Photothermal ablation (PTA) is a promising avenue in the area of cancer therapeutics that destroys tumor cells through conversion of near-infrared (NIR) laser light to heat. Hollow gold nanospheres (HGNs) are one of the few materials that are capable of converting light to heat and have been previously used for photothermal ablation studies. Selective delivery of functional nanoparticles to the tumor site is considered as an effective therapeutic approach. In this paper, we demonstrated the anti-cancer potential of HGNs. HGNs were conjugated with monoclonal antibody (anti-TROP2) in order to target cervical cancer cells (HeLa) that contain abundant trophoblast cell surface antigen 2 (TROP2) on the cell surface. The efficient uptake and intracellular location of these functionalized HGNs were studied through application of inductively coupled plasma atomic emission spectroscopy (ICP-AES) and transmission electron microscopy (TEM). Cytotoxicity induced by PTA was measured using CCK-8 assay. HeLa cells incubated with naked HGNs (0.3-3 nmol L(-1)) within 48 h did not show obvious cytotoxicity. Under laser irradiation at suitable power, anti-TROP2 conjugated HGNs achieved significant tumor cell growth inhibition in comparison to the effects of non-specific PEGylated HGNs (P < 0.05). γH2AX assay results revealed higher occurrences of DNA-DSBs with anti-TROP2 conjugated HGNs plus laser radiation as compared to treatment with laser alone. Flow cytometry analysis showed that the amount of cell apoptosis was increased after laser irradiation with anti-TROP2 conjugated HGNs (P < 0.05). Anti-TROP2 conjugated HGNs resulted in down-regulation of Bcl-2 expression and up-regulation of Bax expression. Our study results confirmed that anti-TROP2 conjugated HGNs can selectively destroy cervical cancer cells through inducing its apoptosis and DNA damages. We propose that HGNs have the potentials to mediate targeted cancer treatment.

Effective photothermal chemotherapy using doxorubicin-loaded gold nanospheres that target EphB4 receptors in tumors.

Photothermal ablation (PTA) is an emerging technique that uses near-infrared (NIR) laser light-generated heat to destroy tumor cells. However, complete tumor eradication by PTA therapy alone is difficult because heterogeneous heat distribution can lead to sublethal thermal dose in some areas of the tumor. Successful PTA therapy requires selective delivery of photothermal conducting nanoparticles to mediate effective PTA of tumor cells, and the ability to combine PTA with other therapy modalities. Here, we synthesized multifunctional doxorubicin (DOX)-loaded hollow gold nanospheres (DOX@HAuNS) that target EphB4, a member of the Eph family of receptor tyrosine kinases overexpressed on the cell membrane of multiple tumors and angiogenic blood vessels. Increased uptake of targeted nanoparticles T-DOX@HAuNS was observed in three EphB4-positive tumors both in vitro and in vivo. In vivo release of DOX from DOX@HAuNS, triggered by NIR laser, was confirmed by dual-radiotracer technique. Treatment with T-DOX@HAuNS followed by NIR laser irradiation resulted in significantly decreased tumor growth when compared with treatments with nontargeted DOX@HAuNS plus laser or HAuNS plus laser. The tumors in 6 of the 8 mice treated with T-DOX@HAuNS plus laser regressed completely with only residual scar tissue by 22 days following injection, and none of the treatment groups experienced a loss in body weight. Together, our findings show that concerted chemo-photothermal therapy with a single nanodevice capable of mediating simultaneous PTA and local drug release may have promise as a new anticancer therapy.

Multifunctional nanocarriers for cell imaging, drug delivery, and near-IR photothermal therapy.

Multifunctional nanocarriers based on chitosan/gold nanorod (CS-AuNR) hybrid nanospheres have been successfully fabricated by a simple nonsolvent-aided counterion complexation method. Anticancer drug cisplatin was subsequently loaded into the obtained hybrid nanospheres, utilizing the loading space provided by the chitosan spherical matrix. In vitro cell experiments demonstrated that the CS-AuNR hybrid nanospheres can not only be utilized as contrast agents for real-time cell imaging but also serve as a near-infrared (NIR) thermotherapy nanodevice to achieve irradiation-induced cancer cell death owing to the unique optical properties endowed by the encapsulated gold nanorods. In addition, an effective attack on the cancer cells by the loaded anticancer drug cisplatin has also been observed, rendering the obtained nanocarriers an all-in-one system possessing drug delivery, cell imaging, and photothermal therapy functionalities.

Intracellular hyperthermia: Nanobubbles and their biomedical applications.

Functionalised nanoparticles have been proposed as potential agents for non-invasive therapies where an external source such as a laser or an electro-magnetic wave is used to heat targeted particles for either drug release or malignant cell damage. It is desirable to have intracellular reactions to minimise the damage to health cells. However, it is still debatable from the thermal response point of view, whether intracellular hyperthermia is better than extracellular delivery due to conventional ideas of localisation of heat by nanoparticles. This work conducts an analytical study on the heating of a single nanoparticle by a pulsed laser and reveals the potential role of the formation of nanobubbles around heated particles. The rapid formation and contraction of bubbles around heated nanoparticles, associated with the propagation of pressure waves, could bring thermal-mechanical damage to surrounding cells at a dimension much larger than that of a nanoparticle. The challenges of the study of nanobubbles are highlighted and their potential healthcare implications are discussed.

Nanosized As2O3/Fe2O3 complexes combined with magnetic fluid hyperthermia selectively target liver cancer cells.

AIM: To study the methods of preparing the magnetic nano-microspheres of Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) complexes and their therapeutic effects with magnetic fluid hyperthermia (MFH). METHODS: Nanospheres were prepared by chemical co-precipitation and their shape and diameter were observed. Hemolysis, micronucleus, cell viability, and LD(50) along with other in vivo tests were performed to evaluate the Fe(2)O(3) microsphere biocompatibility. The inhibition ratio of tumors after Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) injections combined with induced hyperthermia in xenograft human hepatocarcinoma was calculated. RESULTS: Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) particles were round with an average diameter of 20 nm and 100 nm as observed under transmission electron microscope. Upon exposure to an alternating magnetic field (AMF), the temperature of the suspension of magnetic particles increased to 41-51 degrees C, depending on different particle concentrations, and remained stable thereafter. Nanosized Fe(2)O(3) microspheres are a new kind of biomaterial without cytotoxic effects. The LD(50) of both Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) in mice was higher than 5 g/kg. One to four weeks after Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) complex injections into healthy pig livers, no significant differences were found in serum AST, ALT, BUN and Cr levels among the pigs of all groups (P > 0.05), and no obvious pathological alterations were observed. After exposure to alternating magnetic fields, the inhibition ratio of the tumors was significantly different from controls in the Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) groups (68.74% and 82.79%, respectively; P < 0.01). Tumors of mice in treatment groups showed obvious necrosis, while normal tissues adjoining the tumor and internal organs did not. CONCLUSION: Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) complexes exerted radiofrequency-induced hyperthermia and drug toxicity on tumors without any liver or kidney damage. Therefore, nanospheres are ideal carriers for tumor-targeted therapy.