Reversible Thermochromic Nanoparticles Composed of a Eutectic Mixture for Temperature-Controlled Photothermal Therapy.

Photothermal therapy (PTT) is an effective approach to cancer therapy. However, the high temperature during the therapy increases the damage to surrounding normal tissues. Thermochromic material, which exhibits temperature-activated color change and optical absorption, is a promising photothermal agent for precisely temperature-controlled PTT. Nevertheless, the construction of nanosized thermochromic particles with an appropriate transition temperature (44-47 °C) is still a great challenge. Here, thermochromic nanoparticles with the transition temperature at 45 °C based on a leuco dye-developer-solvent system are developed for thermostatic photothermal tumor therapy. Below the temperature, the nanoparticles take a dark green color to absorb light and convert it into heat efficiently. Once the temperature reaches the transition point, the colored nanoparticles switch to a colorless state, maintaining the temperature at the predefined level and allowing deeper light penetration. The autoregulated nanoparticles exhibit a prominent therapeutic effect for the tumor without destroying normal tissues.

Magnetic thermosensitive micelles with upper critical solution temperature for NIR triggered drug release.

Smart micelles which undergo dramatic property changes in response to temperature have aroused extensive interest in specific cancer therapy. To date, studies on thermosensitive polymers have mainly focused on lower critical solution temperature (LCST) polymers. Materials with upper critical solution temperature (UCST) which can swell and disassemble at elevated temperatures have much less been documented, although they have been reported to be ideal carriers for quick and complete drug release upon applying a stimulus. Here, magnetic micelles with UCST are developed for doxorubicin (DOX) delivery. Hydrophobic Fe3O4 magnetic nanoparticles with a particle size of 8 nm are fabricated and enveloped in an amphiphilic polymer, poly(AAm-co-AN)-g-PEG (PAAP), to form UCST micelles (Fe3O4@PAAP). The resulting micelles exhibit excellent photothermal effects and burst drug release in response to near infrared (NIR) laser irradiation. The in vitro and in vivo antitumor experiments indicate that DOX-Fe3O4@PAAP micelles can significantly enhance the therapeutic effect upon NIR light irradiation. A novel thermosensitive platform is thus offered for in situ drug release and combined photothermal-chemotherapy, holding a favorable prospect for cancer therapy.

Alginate/chitosan microcapsules for in-situ delivery of the protein, interleukin-1 receptor antagonist (IL-1Ra), for the treatment of dextran sulfate sodium (DSS)-induced colitis in a mouse model.

Targeted delivery of bioactive compounds such as proteins to the colon has numerous advantages for the therapeutic treatment of inflammatory bowel disease. The present study sought to fabricate alginate/chitosan microcapsules containing IL-1Ra (Alg/Chi/IL-1Ra MC) via a single-step electrospraying method. Two important factors of efficacy were measured-the pH-responsiveness of the microcapsule and the in-vitro drug release profile. The DSS-induced colitis mouse model was used to evaluate the therapeutic effect of the Alg/Chi/IL-1Ra microcapsules, with results showing the protective effect of the Alg/Chi microcapsules for the passage of IL-1Ra through the harsh environment of the upper gastrointestinal tract. This effect was owing to the pH-sensitive response of the microcapsule, which allowed the targeted release of IL-1Ra in the colon. DAI evaluation, colon length, colon tissue morphology, histologic damage scores and relative protein concentrations (MPO, TNF-α and IL-1ß) demonstrated that the Alg/Chi/IL-1Ra microcapsules alleviated DSS-induced colitis in mice. The present study thus demonstrates a practical means of oral delivery of proteins, in-situ colon release, and a promising application of IL-1Ra in the treatment of autoimmune and inflammatory diseases.

Magnetic liposomes for light-sensitive drug delivery and combined photothermal-chemotherapy of tumors.

The targeted delivery of anticancer drugs for improving the therapeutic efficacy and reducing the side effects has attracted great attention in cancer therapy. In this study, multifunctional magnetic nanoparticles-loaded thermosensitive liposomes (Fe3O4-TSL) were developed for the near-infrared (NIR) laser-triggered release and combined photothermal-chemotherapy of tumors. Doxorubicin (DOX) was encapsulated into the Fe3O4-TSL (DOX-Fe3O4-TSL) via an ammonium sulfate gradient, with an encapsulation efficiency of up to 90.9%. Once treated with NIR laser irradiation, significantly improved drug release was observed in the DOX-Fe3O4-TSL compared to that of DOX-TSL. After an intravenous injection, Fe3O4-TSL tended to enrich in the tumor over time and showed remarkable magnetic resonance imaging (MRI) and photothermal effects. The combined chemo-photothermal therapy study demonstrated that DOX-Fe3O4-TSL could significantly inhibit the tumor growth without causing any significant damage to normal tissues under NIR laser irradiation. These results revealed a great potential for DOX-Fe3O4-TSL for the diagnosis and synergistic therapy of tumors.

Engineered nanoparticles disguised as macrophages for trapping lipopolysaccharide and preventing endotoxemia.

Endotoxemia is a severe pathophysiology induced by bacterial endotoxin (also known as lipopolysaccharide, LPS), causing high mortality in clinic due to the life-threatening syndromes, such as sepsis, shock, and multiple organ dysfunction. Removing or neutralizing endotoxin from the circulatory system has been proven to be a potential strategy for the treatment of endotoxemia. However, the selectivity and removal efficiency of existing detoxification approaches are not satisfied. Considering the crucial role of immune cells in LPS recognition and inflammation mediation, we design a disguised nanoparticle using macrophage membranes as bait to specifically capture and deactivate LPS. The in vivo experiment results demonstrate that the nanoparticles markedly weaken the immune response, reduce the inflammatory reaction, and improve the survival rate of endotoxic mice. These deceptive nanoparticles should be broadly applicable for treating a variety of diseases related to LPS, such as metabolic and vascular abnormalities in obesity, and diabetes-related diseases.

Intracerebroventricular streptozotocin-induced Alzheimer's disease-like sleep disorders in rats: Role of the GABAergic system in the parabrachial complex.

AIM: Sleep disorders are common in Alzheimer's disease (AD) and assumed to directly influence cognitive function and disease progression. This study evaluated sleep characteristics in a rat model of AD that was induced by intracerebroventricular streptozotocin (STZ) administration and assessed the possible underlying mechanisms. METHODS: Cognition ability was assessed in the Morris water maze in rats. Sleep parameters were analyzed by electroencephalographic and electromyographic recordings. Neuronal activity in brain areas that regulate sleep-wake states was evaluated by double-staining immunohistochemistry. High-performance liquid chromatography with electrochemical detection was used to detect neurotransmitter levels. RESULTS: Fourteen days after the STZ injection, the rats exhibited sleep disorders that were similar to those in AD patients, reflected by a significant increase in wakefulness and decreases in nonrapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. The c-Fos expression analysis indicated that neuronal activity and the number of neurons in the dorsal raphe nucleus and locus coeruleus decreased in STZ-injected rats. In the ventrolateral preoptic nucleus (VLPO), the activity of γ-aminobutyric acid (GABA) neurons was suppressed. In the arousal-driving parabrachial nucleus (PBN), GABAergic activity was suppressed, whereas glutamatergic activity was promoted. The neurotransmitter analysis revealed a reduction in GABA in the VLPO and PBN and elevation of glutamate in the PBN. A direct injection of the GABAA receptor antagonist bicuculline in the PBN in normal rats induced a similar pattern of sleep disorder as in STZ-injected rats. A microinjection of GABA in the PBN improved sleep disorders that were induced by STZ. CONCLUSION: These results suggest that the reduction in GABAergic inhibition in the PBN and VLPO may be involved in sleep disorders that are induced by STZ. Our novel findings encourage further studies that investigate mechanisms of sleep regulation in sporadic AD.

Effect of magnetic nanoparticles size on rheumatoid arthritis targeting and photothermal therapy.

Nanoparticles based multifunctional system exhibits great potential in diagnosis and therapy of rheumatoid arthritis (RA). The size of nanoparticles plays an essential role in biodistribution and cellular uptake, in turn affects the drug delivery efficiency and therapeutic effect. To investigate the optimal size for RA targeting, Fe3O4 nanoparticles with well-defined particle sizes (70-350 nm) and identical surface properties were developed as model nanoparticles. The synthesized Fe3O4 nanoparticles exhibited excellent biocompatibility and showed higher temperature response under irradiation of near infrared light. Size-dependent internalization was observed when incubated with inflammatory cells. Compared with large ones, small nanoparticles were more readily be phagocytized, leading to higher cytotoxicity in vitro. However, the in vivo experiment in CIA mice demonstrated a quite different result that nanoparticles with size of 220 nm exerted better accessibility to inflamed joint and resulted in higher temperature and better therapeutic effect under laser irradiation. This study not only offered a novel method for RA therapy but also a guideline for RA targeted drug carrier design.

Formulation and in vitro stability evaluation of ethosomal carbomer hydrogel for transdermal vaccine delivery.

The primary objective of this study was to develop, evaluate and compare the effectiveness and stability of ethosomal carbomer gels in different solvents. The optimal ethosomal formulation was isolated to create ethosomal gels using carbomer in either pure water (water gel) or PBS containing 30% ethanol (PBS gel). In vitro release of the ethosomal gels were tested using Franz apparatus on hydrophilic and hydrophobic artificial membranes. In vitro stability of two ethosomal gels was systematically evaluated. Transdermal antigen delivery of ethosomal gel was finally performed on the skin of hair removal mice. Both solvent and concentration effects on the in vitro release performance of ethosomal gel of carbomer have been confirmed. Penetration depth has been found to be dependent on the nature of the membranes such that penetration rate is higher in the hydrophobic membrane than the hydrophilic ones. Furthermore, in vitro stability test indicated that ethosomal PBS gel was more stable than ethosomal water gel. In vivo immunoassay confirmed that the ethosomal PBS gel could deliver the antigenic molecules into the skin of mice and stimulate specific IgG secretion. Using the same solvent for lipid vesicular formulation when making polymeric hydrogel may help to provide a more conducive environment for lipid vesicles and hence enhance their roles in transdermal antigen delivery.

Rapid Quantitative Analysis of Naringenin in the Fruit Bodies of Inonotus vaninii by Two-phase Acid Hydrolysis Followed by Reversed Phase-high Performance Liquid Chromatography-ultra Violet.

INTRODUCTION: Sanghuang is one of mystical traditional Chinese medicines recorded earliest 2000 years ago, that included various fungi of Inonotus genus and was well-known for antitumor effect in modern medicine. Inonotus vaninii is grown in natural forest of Northeastern China merely and used as Sanghuang commercially, but it has no quality control specification until now. This study was to establish a rapid method of two-phase acid hydrolysis followed by reversed phase-high performance liquid chromatography-ultra violet (RP-HPLC-UV) to quantify naringenin in the fruit body of I. vaninii. MATERIALS AND METHODS: Sample solution was prepared by pretreatment of raw material in two-phase acid hydrolysis and the hydrolysis technology was optimized. After reconstitution, analysis was performed using RP-HPLC-UV. The method validation was investigated and the naringenin content of sample and comparison were determined. RESULTS: The naringenin was obtained by two-phase acid hydrolysis method, namely, 10.0 g of raw material was hydrolyzed in 200 mL of 1% sulfuric acid aqueous solution (v/v) and 400 mL of chloroform in oil bath at 110°C for 2 h. Good linearity (r = 0.9992) was achieved between concentration of analyte and peak area. The relative standard deviation (RSD) of precision was 2.47% and the RSD of naringenin contents for repeatability was 3.13%. The accuracy was supported with recoveries at 96.37%, 97.30%, and 99.31%. The sample solution prepared using the proposed method contained higher content of naringenin than conventional method and was stable for 8 h. CONCLUSION: Due to the high efficiency of sample preparation and high reliability of the HPLC method, it is feasible to use this method for routine analysis of naringenin in the fungus. SUMMARY: A convenient two-phase acid hydrolysis was employed to produce naringenin from raw material, and then an efficient and reliable reversed phase-high performance liquid chromatography-ultra violet method was established to monitor naringenin in the fruit bodies of Inonotus vaninii. The newly established method could be used to control the quality of the herb. Abbreviations used: RP-HPLC-UV: Reversed Phase-High Performance Liquid Chromatography-Ultra Violet, RSD: Relative Standard Deviation, EtOAc: Ethyl acetate, ACN: Acetonitrile, MeOH: Methanol, RH: Relative Humility.

[Absorption enhancing effects and safety of PAMAM dendrimers on liquiritin].

PAMAM dendrimer is one of the most widely studied dendrimers in recent years, which has a large number of functional groups on the surface and cavities inside, specific three-dimensional structure and good biocompatibility, permeability and stability. It has been widely applied in drug and gene carrier fields and may become a new absorption enhancer. In order to study the absorption enhancing effects of PAMAM dendrimers, liquiritin was selected as the model drug, with the protection of spleen and liver, detoxification and other functions, but it had not been widely used in clinical application because of its difficult absorption, first pass effect, and low bioavailability. This topic was based on the two main determinants (solubility and permeability) of intestinal absorption in the body, researched the physicochemical properties of liquiritin, analyzed the transport volume of liquiritin with or without PAMAM dendrimers by using Caco-2 cell model, and analyzed the cytotoxicity of PAMAM dendrimers on Caco-2 cells by MTT experiments. These results showed that 0.1% of the G4 generation PAG can promote the absorption of liquiritin safely and effectively, and it was suitable for further development into a new type of pharmaceutical excipients.

Near-infrared light-responsive nanoparticles with thermosensitive yolk-shell structure for multimodal imaging and chemo-photothermal therapy of tumor.

Thermosensitive yolk-shell nanoparticles were developed as remote-controlled targeting drug delivery platform for multimodal imaging and combined therapy of cancer. The nanoparticles were fabricated using magnetic Fe3O4 nanoparticles as photothermal cores, thermo-responsive poly(N-isopropylacrylamide)-co-1-Vinyl-2-pyrrolidone p(NIPAM-co-NVP) as shells (Fe3O4-PNIPAM), with a hollow space between the two layers for loading of chemotherapeutic drug. The magnetic iron oxide nanoparticle cores could absorb and transform light to heat efficiently upon the irradiation of near infrared (NIR) laser, resulting in the shrink of the PNIPAM shell and the release of chemo-drugs. In vivo fluorescence/photoacoustic images demonstrated that Fe3O4-PNIPAM nanoparticles could accumulate in the tumor after intravenous injection. Upon the irradiation of the NIR laser, DOX-Fe3O4-PNIPAM nanoparticles exhibited outstanding synergistic effect. The tumor inhibition rate increased from 40.3% (DOX-Fe3O4-PNIPAM alone) and 65.2% (Fe3O4-PNIPAM +NIR) to 91.5%. The results demonstrated that the NIR-responsive nanocarrier offers a novel strategy for cancer theranostics and combined therapy of cancer.

Remotely controlled drug release based on iron oxide nanoparticles for specific therapy of cancer.

Chemotherapy has been widely used in clinic and usually causes serious side effects. To improve therapeutic effect, it is really necessary to realize local drug release and specific therapy. In this work, we demonstrate Azo (4,4-azobis (4-cyanovaleric acid))-functionalized multifunctional nanoparticles to realize near-infrared (NIR) laser-responsive drug release and combined chemo-photothermal cancer therapy. Doxorubicin (DOX) was attached to magnetic nanoparticles via a thermal-cleavable Azo linker, which could decompose while the temperature reach ∼43°C. The Azo-functioned Fe3O4 NPs also showed good capability as a contrast for T2-weighted magnetic resonance (MR) images in vivo. After intravenous injection, the Fe3O4-Azo NPs could targeted accumulate in the tumor. Once exposed to NIR irradiation, Fe3O4 nanoparticles (NPs) absorb NIR light to generate heat rapidly, resulting in the tumor specific DOX release and remarkable tumor growth inhibition effect. The Azo-functionalized Fe3O4 NPs with multifunction of in vivo imaging and combined therapy present a potential for tumor diagnosis treatment.

Simultaneous delivery of anti-miR21 with doxorubicin prodrug by mimetic lipoprotein nanoparticles for synergistic effect against drug resistance in cancer cells.

The development of drug resistance in cancer cells is one of the major obstacles to achieving effective chemotherapy. We hypothesized that the combination of a doxorubicin (Dox) prodrug and microRNA (miR)21 inhibitor might show synergistic antitumor effects on drug-resistant breast cancer cells. In this study, we aimed to develop new high-density lipoprotein-mimicking nanoparticles (HMNs) for coencapsulation and codelivery of this potential combination. Dox was coupled with a nuclear localization signal (NLS) peptide to construct a prodrug (NLS-Dox), thereby electrostatically condensing miR21 inhibitor (anti-miR21) to form cationic complexes. The HMNs were formulated by shielding these complexes with anionic lipids and Apo AI proteins. We have characterized that the coloaded HMNs had uniformly dispersed distribution, favorable negatively charged surface, and high coencapsulation efficiency. The HMN formulation effectively codelivered NLS-Dox and anti-miR21 into Dox-resistant breast cancer MCF7/ADR cells and wild-type MCF7 cells via a high-density-lipoprotein receptor-mediated pathway, which facilitated the escape of Pgp drug efflux. The coloaded HMNs consisting of NLS-Dox/anti-miR21 demonstrated greater cytotoxicity with enhanced intracellular accumulation in resistant MCF7/ADR cells compared with free Dox solution. The reversal of drug resistance by coloaded HMNs might be attributed to the suppression of miR21 expression and the related antiapoptosis network. Furthermore, the codelivery of anti-miR21 and NLS-Dox by HMNs showed synergistic antiproliferative effects in MCF7/ADR-bearing nude mice, and was more effective in tumor inhibition than other drug formulations. These data suggested that codelivery of anti-miR21 and chemotherapeutic agents by HMNs might be a promising strategy for antitumor therapy, and could restore the drug sensitivity of cancer cells, alter intracellular drug distribution, and ultimately enhance chemotherapeutic effects.

[Application of magnetic iron oxide nanoparticles in magnetic resonance / photothermal dual-modal imaging].

In this study, water-dispersible magnetic iron oxide (Fe3O4) nanoparticles were synthesized with solvothermal method. The nanoparticles were characterized with a transmission electron microscopy (TEM) and vibrating sample magnetometer (VSM). The in vitro magnetic resonance response and photothermal conversion characteristics of the nanoparticles were evaluated. In addition, the cellular uptake, cytotoxicity and biodistribution were studied. Finally, magnetic resonance/photothermal dual-modal imaging effect of the as-synthesized Fe3O4 nanoparticles was investigated in the tumor-bearing mice. The results showed that the obtained magnetic nanoparticles were uniform with a mean diameter of about 125 nm. Moreover, the superparamagnetic Fe3O4 nanoparticles showed remarkable magnetic resonance response and photothermal conversion properties. The results of cellular experiments showed that the cell viability was nearly 85% even the concentration of the nanoparticles was up to 1 000 µg·mL−1, an indicator of good biocompatibility. In addition, the nanoparticles could be taken up by the tumor cells and then located in the cytoplasm. After intravenous injection, the nanoparticles were tended to enrich in the tumor over time, which is helpful in achieving dual-modal magnetic resonance/photothermal imaging. In sum, the obtained Fe 3O4 nanoparticles showed great potential to be applied for multi-modal bio-imaging which may play an important role in the diagnosis of tumors.

Targeted Biomimetic Nanoparticles for Synergistic Combination Chemotherapy of Paclitaxel and Doxorubicin.

Codelivery of multiple chemotherapeutics has become a versatile strategy in recent cancer treatment, but the antagonistic behavior of combined drugs limited their application. We developed a recombinant high-density lipoprotein (rHDL) nanoparticle for the precise coencapsulation and codelivery of two established drugs and hypothesized that they could act synergistically to improve anticancer efficacy. The coloaded rHDL was formulated by passively incorporating hydrophobic paclitaxel (PTX), and subsequently remotely loading hydrophilic doxorubicin (Dox) into the same nanoparticles. The resultant rHDL system restored targeted delivery function toward cancer cells via scavenger receptor class B (SR-BI), as confirmed by in vitro confocal imaging and flow cytometry. These coloaded rHDL nanoparticles were remarkably effective in increasing the ratiometric accumulation of drugs in cancer cells and enhancing antitumor response at synergistic drug ratios. In particular, they exhibited more efficacious anticancer effects in an in vitro cytotoxicity evaluation and in a xenograft tumor model of hepatoma compared with free drug cocktail solutions. These results confirm that the coloaded rHDL nanoparticles are promising candidates for the synergistic delivery of drugs with diverse physicochemical properties in cancer treatment integrating efficiency and safety considerations.

Azo-functionalized Fe3O4 nanoparticles: a near-infrared light triggered drug delivery system for combined therapy of cancer with low toxicity.

To improve the therapeutic effect and decrease the toxicity in normal tissues, stimuli-responsive drug delivery systems have attracted extensive attention in tumor therapy. In this work, we present a smart drug delivery system based on the stimulated decomposition of a thermo-sensitive molecule, azobis[N-(2-carboxyethyl)-2-methylpropionamidine] (Azo), for the combined photothermal therapy and chemotherapy. Doxorubicin (DOX) was attached to the surface of magnetic nanoparticles (NPs) via the Azo linker. Upon irradiation with near infrared (NIR) light, local heating is generated by iron oxide nanoparticles (IONPs), which triggers the decomposition of the Azo molecule and the release of DOX. Compared with Fe3O4-DOX NPs, Fe3O4-Azo-DOX NPs demonstrate dominant advantages of stability, which results in the low toxicity of Fe3O4-Azo-DOX NPs in cardiac tissues. Fe3O4-Azo NPs display excellent photothermal effects under NIR laser irradiation and extremely low cytotoxicity towards MCF-7 cells. Furthermore, the Fe3O4-Azo-DOX NP system exhibits significantly enhanced cell killing effects upon irradiation with NIR, attributed to the synergistic therapeutic efficacy of photothermal chemotherapy.

Core-shell structured Fe3O4@TiO2-doxorubicin nanoparticles for targeted chemo-sonodynamic therapy of cancer.

To facilitate targeting drug delivery and combined therapy, we develop titanium dioxide-encapsulated Fe3O4 nanoparticles (Fe3O4@TiO2 NPs). Titanium dioxide (TiO2), which is employed as a sonosensitizer for sonodynamic therapy (SDT), can also be used for the loading of doxorubicin (DOX). The fabricated Fe3O4@TiO2 NPs exhibit pH-dependent loading and release of doxorubicin (DOX) in vitro. After incubation with cancer cells, reactive oxygen species (ROS) are generated efficiently upon the irradiation of ultrasound. In the biodistribution experiments, extremely high in vivo tumor accumulation of Fe3O4@TiO2 NPs and long-time retention effect are observed. Compared with chemotherapy or sonodynamic treatment alone, the combined therapy demonstrated a synergistic effect, resulting in stronger cytotoxicity and higher therapeutic efficacy. Thus, the constructed NPs are endowed with multifunctions which allow them to selectively deliver combinatorial therapeutic payload to tumor with enhanced therapeutic effectiveness and minimal side effects.

Negative-charge-functionalized mesoporous silica nanoparticles as drug vehicles targeting hepatocellular carcinoma.

In this paper, a series of doxorubicin-loaded and negative-charge-functionalized mesoporous silica nanoparticles (DOX-MSN/COOH) was successfully prepared and used for imaging and targeting therapy of hepatocellular carcinoma. The nanoparticles were uniform and negatively charged, with a diameter of about 55 nm, and a zeta potential of -20 mV. In vitro study showed that the nanoparticles could easily be endocytosed by liver cancer cells (HepG2) and were well-accumulated in the liver by passive targeting. In vivo study proved the ability of DOX-MSN/COOH to inhibit the tumor growth and prolong the survival time of mice bearing hepatocellular carcinoma in situ, giving better results than free DOX. More importantly, histological examination showed no histopathological abnormalities of normal liver cells and heart cells after the administration of DOX-MSN/COOH, while the treatment with free DOX caused damage to those cells. In conclusion, DOX-MSN/COOH exhibited enhanced antitumor efficacy as well as reduced side effects for liver cancer therapy.

Dual-core@shell-structured Fe3O4-NaYF4@TiO2 nanocomposites as a magnetic targeting drug carrier for bioimaging and combined chemo-sonodynamic therapy.

Multifunctional dual-core@shell (Fe3O4-NaYF4@TiO2) nanocomposite (DCSNC) loaded with doxorubicin (DOX) have been developed for synergetic sonodynamic cancer chemotherapy, where titanium dioxide (TiO2) is employed as a sonosensitizer for sonodynamic therapy (SDT) of the tumor in deep tissues, and NaYF4 is used for upconversion luminescence (UCL) imaging. After being coated with hyaluronic acid (HA), the nanocomposites exhibit a time dependent cellular uptake and an excellent nucleus targeting effect in KB and MCF-7 cells. The ultrasound of HA-DCSNCs obviously enhances the apoptosis rate of MCF-7 cells. A greater tumor inhibition rate is observed when the tumor-bearing mice are treated with combined therapy (88.36%) compared with chemotherapy (28.36%) or sonodynamic therapy (38.91%) alone, indicating the potential of sonodynamic chemotherapy for cancer treatment.

CMCTS stabilized Fe3O4 particles with extremely low toxicity as highly efficient near-infrared photothermal agents for in vivo tumor ablation.

With the potential uses of photothermal therapy (PTT) in cancer treatment with excellent efficacy, and the growing concerns about the nanotoxicity of hyperthermia agents such as carbon nanotubes and gold-based nanomaterials, the importance of searching for a biocompatible hyperthermia agent cannot be emphasized too much. In this work, a novel promising hyperthermia agent employing magnetic Fe3O4 particles with fairly low toxicity was proposed. This hyperthermia agent showed rapid heat generation under NIR irradiation. After modification with carboxymethyl chitosan (CMCTS), the obtained Fe3O4@CMCTS particles could disperse stably in PBS and serum without any aggregation. The modification of CMCTS could decrease the adsorption of bovine serum albumin (BSA) and improve the cellular uptake. In a comparative study with hollow gold nanospheres (HAuNS), Fe3O4@CMCTS particles exhibited a comparable photothermal effect and fairly low cytotoxicity. The in vivo magnetic resonance (MR) images of mice revealed that by attaching a magnet to the tumor, Fe3O4@CMCTS particles accumulated in the tumor after intravenous injection and showed a low distribution in the liver. After being exposed to a 808 nm laser for 5 min at a low power density of 1.5 W cm(-2), the tumors on Fe3O4@CMCTS-injected mice reached a temperature of ~52 °C and were completely destroyed. Thus, a kind of multifunctional magnetic nanoparticle with extremely low toxicity and a simple structure for simultaneous MR imaging, targeted drug delivery and photothermal therapy can be easily fabricated.