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As nanomedicine-based clinical strategies have continued to develop, the possibility of combining chemotherapy and singlet oxygen-dependent photodynamic therapy (PDT) to treat pancreatic cancer (PaC) has emerged as a viable therapeutic modality. The efficacy of such an approach, however, is likely to be constrained by the mechanisms of drug release and tumor oxygen levels. In the present study, we developed an Fe(III)-complexed porous coordination network (PCN) which we then used to encapsulate PTX (PCN-Fe(III)-PTX) nanoparticles (NPs) in order to treat PaC via a combination of chemotherapy and PDT. The resultant NPs were able to release drug in response to both laser irradiation and pH changes to promote drug accumulation within tumors. Furthermore, through a Fe(III)-based Fenton-like reaction these NPs were able to convert H2O2 in the tumor site to O2, thereby regulating local hypoxic conditions and enhancing the efficacy of PDT approaches. Also these NPs were suitable for use as a T1-MRI weighted contrast agent, making them viable for monitoring therapeutic efficacy upon treatment. Our results in both cell line and animal models of PaC suggest that these NPs represent an ideal agent for mediating effective MRI-guided chemotherapy-PDT, giving them great promise for the clinical treatment of PaC.

Constructing nanocarriers with high drug loading capacity is a challenge, which limits the effective delivery of drugs to solid tumors. Here, we reported a one-pot synthesis of hollow nanoparticles (NPs) encapsulated by doxorubicin (DOX) and modified with polydopamine (PDA) to form PDA@DOX NPs for breast cancer treatment. PDA@DOX NPs demonstrated exceptionally high capacity (53.16%) for loading DOX. In addition, when PDA@DOX NPs were administered systemically, they exhibited responsive aggregation in the tumor sites and demonstrated a good controlled release effect for DOX due to the weak acidic environment of the tumor sites and targeting near-infrared (NIR) light irradiation. The PDA outer layer absorbed the near-infrared (NIR) light and facilitated simultaneous generation of heat energy for destroying the tumor cells to release the drug upon NIR irradiation. Moreover, this NIR-activated combined/synergistic therapy exhibited remarkably complete tumor growth suppression in a breast cancer mouse model. Importantly, NPs exhibited a good ultrasound performance both in vitro and in vivo, which could monitor the treatment process. In conclusion, this NIR-activated PDA@DOX NP system is demonstrated as a good US-guided combination (chemotherapy + PTT) therapy platform with high loading capacity and controlled drug release characteristics, which is promising for the treatment of breast cancer.

Mitochondria-targeted mild-temperature photothermal therapy (MT-PTT) is a promising strategy that can maximize anticancer effects and reduce adverse reactions. Here, a novel photosensitizer with mitochondrial targeting based on IR780 iodide and heat shock protein 90 inhibitor (BIIB021), which can passively accumulate in MCF-7 cells and achieve effective MT-PTT effect is synthesized. The prepared PEG-IR780-BIIB021 nano-micelles possess considerable biocompatibility and biological stability, with an encapsulation efficiency of about 84% for BIIB021. They can selectively enrich in mitochondria, and release BIIB021 after NIR irradiation to reduce cell tolerance to heat, thereby reducing the mitochondrial membrane potential and rapidly affecting key intrinsic apoptotic factors (Cyt-C, Caspase-9, Bcl-2 and Bax) to achieve the effect of MT-PTT. It is believed that mitochondria-targeted MT-PTT generated by the PEG-IR780-BIIB021 nano-micelles is a promising therapeutic strategy in clinical practice.

The antimicrobial peptides (AMPs) are a group of unique naturally occurring anti-microbial compounds with around 50 amino acids. It represents promising therapeutic agents to the infectious disease without concerning about drug resistance. However, commercial development of these peptides for even the simplest application has been hindered by the limitations of sources, instability, toxicity and bioavailability. To improve the properties of the artificial synthesized AMPs, the modification and design are the hotspots of the AMPs research. In fact, more than half of the known AMPs are naturally modified. In this review, two types of modification strategies, biochemical modification and chemical modification were summarized. Although, the chemical modification is versatile and direct, the manufacturing cost is greatly increased compared to the antibiotics. With the recent progress of the protein modification enzyme, the biochemical modification of the antimicrobial peptide followed by heterologous expression has great application prospects.

The recently emerged exceedingly small magnetic iron oxide nanoparticles (ES-MIONs) (

A colorimetric assay is proposed for the selective detection of Cr(iii) and Cr(vi) via the aggregation-induced color change of gallic acid capped gold nanoparticles (GA-AuNPs). The AuNPs are characterized using UV-vis spectroscopy, transmission electron microscopy (TEM), dynamic light scattering (DLS) and Fourier-transform infrared spectrometry (FT-IR). To detect Cr(iii) and Cr(vi) coexisting in a sample, citrate and thiosulfate were applied to mask Cr(vi) for the detection of Cr(iii), and ethylenediaminetetraacetic acid disodium salt (EDTA) was applied to mask Cr(iii) for the detection of Cr(vi). At optimized experimental conditions, the selectivity of these AuNPs-based detection systems is excellent for Cr(iii) and/or Cr(vi) compared with other types of metal ions. The limit of detections (LODs) of a mixture of Cr(iii) and Cr(vi), Cr(iii) and Cr(vi) by eye vision are 1.5, 1.5 and 2 μM, respectively, and those by UV-vis spectroscopy are 0.05, 0.1 and 0.1 μM, respectively. The minimum detectable concentrations for Cr(iii) or Cr(vi) are all below the guideline value set by the US Environmental Protection Agency (EPA). The applicability of the AuNPs-based colorimetric sensor is also validated by the detection of Cr(iii) and Cr(vi) in electroplating wastewater and real water samples with high recoveries.

The combination therapy has exhibited important potential for the treatment of cancers, especially for drug-resistant cancers. In this report, bi-functional nanoprobes based on doxorubicin (DOX)-loaded NaYF4:Yb/Tm–TiO2 inorganic photosensitizers (FA-NPs-DOX) were synthesized for in vivo near infrared (NIR)-triggered inorganic photodynamic therapy (PDT) and enhanced chemotherapy to overcome the multidrug resistance (MDR) in breast cancers. Using the up-conversion luminescence (UCL) performance of NaYF4:Yb/Tm converting near-infrared (NIR) into ultraviolent (UV) lights, reactive oxygen species (ROS) were triggered from TiO2 inorganic photosensitizers for PDT under the irradiation of a 980 nm laser, by which the deep-penetration and low photo-damage could be reached. Moreover, nanocarrier delivery and folic acid (FA) targeting promoted the cellular uptake, and accelerated the release of DOX in drug-sensitive MCF-7 and resistant MCF-7/ADR cells. The toxicity assessment in vitro and in vivo revealed the good biocompatibility of the as-prepared FA-NPs-DOX nanocomposites. By the combination of enhanced chemotherapy and NIR-triggered inorganic PDT, the viability of MCF-7/ADR cells could decrease by 53.5%, and the inhibition rate of MCF-7/ADR tumors could increase up to 90.33%, compared with free DOX. Therefore, the MDR of breast cancers could be obviously overcome by enhanced chemotherapy and NIR-triggered inorganic PDT of FA-NPs-DOX nanocomposites under the excitation of a 980 nm laser.

Magnetic resonance imaging (MRI), a sophisticated promising three-dimensional tomographic noninvasive diagnostic technique, has an intrinsic advantage in safety compared with radiotracer and optical imaging modalities; however, MRI contrast agents are less sensitive than complexes used in other imaging techniques. Usually the clinically used Gd-based complexes MRI-T1 contrast agents are toxic; therefore, the demand for nontoxic novel T1-weighted MRI candidates with ultrasensitive imaging and advanced functionality is very high. In this research, silica-coated ultra-small monodispersed super-paramagnetic iron oxide nanoparticles were synthesized via a thermal decomposition method, which demonstrated themselves as a high performance T1-weighted MRI contrast agent for heart, liver, kidney and bladder based on in vivo imaging analyses. Transmission electron microscopy (TEM) results illustrated that the diameter of the SPIONPs was in the range of 4 nm and the average size of Fe3O4@SiO2 was about 30-40 nm. X-ray diffraction (XRD) and Raman spectroscopy analyses revealed the phase purity of the prepared SPIONPs. These magnetite nanoparticles exhibited a weak magnetic moment at room temperature because of the spin-canting effect, which promoted a high positive signal enhancement ability. MTT assays and histological analysis demonstrated good biocompatibility of the SPIONPs in vitro and in vivo. In addition, the silica-coated ultra-small (4 nm sized) magnetite nanoparticles exhibited a good r1 relaxivity of 1.2 mM-1 s-1 and a low r2/r1 ratio of 6.5 mM-1 s-1. In vivo T1-weighted MR imaging of heart, liver, kidney and bladder in mice after intravenous injection of nanoparticles further verified the high sensitivity and biocompatibility of the as-synthesized magnetite nanoparticles. These results reveal silica-coated SPIONPs as a promising candidate for a T1 contrast agent with extraordinary capability to enhance MR images.

Photodynamic therapy (PDT) is a promising treatment modality for cancer and other malignant diseases, however safety and efficacy improvements are required before it reaches its full potential and wider clinical use. Herein, we investigated a highly efficient and safe photodynamic therapy procedure by developing a high/low power density photodynamic therapy mode (high/low PDT mode) using methoxypoly(ethylene glycol) thiol (mPEG-SH) modified gold nanorod (GNR)-AlPcS4 photosensitizer complexes. mPEG-SH conjugated to the surface of simple polyelectrolyte-coated GNRs was verified using Fourier transform infrared spectroscopy; this improved stability, reduced cytotoxicity, and increased the encapsulation and loading efficiency of the nanoparticle dispersions. The GNR-photosensitizer complexes were exposed to the high/low PDT mode (high light dose = 80 mW/cm(2) for 0.5 min; low light dose = 25 mW/cm(2) for 1.5 min), and a high PDT efficacy leads to approximately 90% tumor cell killing. Due to synergistic plasmonic photothermal properties of the complexes, the high/low PDT mode demonstrated improved efficacy over using single wavelength continuous laser irradiation. Additionally, no significant loss in viability was observed in cells exposed to free AlPcS4 photosensitizer under the same irradiation conditions. Consequently, free AlPcS4 released from GNRs prior to cellular entry did not contribute to cytotoxicity of normal cells or impose limitations on the use of the high power density laser. This high/low PDT mode may effectively lead to a safer and more efficient photodynamic therapy for superficial tumors. (C) 2014 Elsevier Ltd. All rights reserved.

The aim of this study is to explore an improved double emulsion technology with in situ reaction of lysine (Lys) and glutaraldehyde (GA) for fabricating autofluorescent Lys-poly(lactic-co-glycolic acid)-GA (Lys-PLGA-GA) microcapsules as novel ultrasonic/fluorescent dual-modality contrast agents. Scanning electron microscope (SEM) and static light scattering (SLS) results show that 80% of the Lys-PLGA-GA microcapsules are larger than 1.0 mu m and 90% of them are smaller than 8.9 mu m. SEM and laser confocal scanning microscope (LCSM) data demonstrate that the structure of our Lys-PLGA-GA microcapsules is hollow. Compared with the FT-IR spectrum of PLGA microcapsules, a new peak at 1644 cm(-1) in that of Lys-PLGA-GA microcapsules confirms the formed Schiff base in Lys-PLGA-GA microcapsules. LCSM images and fluorescence spectra show that our Lys-PLGA-GA microcapsules exhibit bright and stable autofluorescence without conjugation to any fluorescent agent, which can be ascribed to the n-pi* transitions of the C=N bonds in the formed Schiff base. Our autofluorescent Lys-PLGA-GA microcapsules might have more wide applications than traditional fluorescent dyes because their excitation and emission spectra are both broad. The fluorescence intensity can also be tuned by the feeding amount of Lys and GA. The MTT assays reveal that the autofluorescent microcapsules are biocompatible. The results of fluorescent imaging in cells and in vitro ultrasonic imaging demonstrate the feasibility of our autofluorescent Lys-PLGA-GA microcapsules as ultrasonic/fluorescent dual-modality contrast agents. This novel ultrasonic/fluorescent dual-modality contrast agent might have potential for a variety of biological and medical applications. (C) 2014 Elsevier B.V. All rights reserved.

Cadmium is a cytotoxic, carcinogenic, and mutagenic industrial product or byproduct. The correlation between metal exposure and microsatellite instability (MSI) has been reported by several groups. In the present study, 50 C57BL/6J mice at 6 weeks of age were divided into five groups and intraperitoneally injected with 0, 0.25, 0.5, 1, or 2 mg/kg cadmium chloride quaque die alterna for 4 weeks. Then, the liver, kidney, testis, leukocytes, bone marrow, and small intestine were collected from the treated mice and weighed. Portions of these tissues were fixed for further histological analysis, and the remaining tissues were subjected to genomic DNA extraction for the analysis of a panel of 42 microsatellite markers. The liver and testis weight coefficients were significantly changed in the 1 and 2 mg/kg cadmium chloride-treated groups compared with the control group. Simultaneously, severe histopathologic changes in the liver and kidneys, along with a complete disorganization of testicular structure and obvious severe necrosis in the testes were observed in the cadmium-treated group. The cadmium accumulated in the liver and kidneys of the mice in all cadmium-treated groups; the tissue cadmium concentrations were significantly higher than those in the control group. After STR scanning, MSI was found at three loci (D15Mit5, D10Mit266, and DxMit172) in the kidneys and leukocytes of mice in the lower dose groups (0.25 and 0.5 mg/kg). In summary, we have successfully established a sub-chronic cadmium exposure model and confirmed that cadmium exposure can induce MSI in mice. We also identified two loci that could be regarded as "hotspots" of microsatellite mutation in mice.

Background The consumption of n-3 polyunsaturated fatty acids (PUFAs) is important to human health, especially in cases of cardiovascular disease. Although beneficial effects of n-3 PUFAs have been observed in a number of studies, the mechanisms involved in these effects have yet to be discovered. Methods We generated hfat-1 transgenic pigs with traditional somatic cell nuclear transfer (SCNT) technology. The fatty acid composition in ear tissue of pigs were detected with gas chromatography. The cholesterol, triglycerides (TAG) and inflammation mediators in circulation were investigated. Results The hfat-1 transgenic pigs were developed which accumulate high levels of n-3 PUFAs than wild-types pigs. Gas chromatography results demonstrated that the total n-3 PUFAs in the ear tissues of the transgenic founders were 2-fold higher than the wild-type pigs. A lipid analysis demonstrated that the levels of TAG in the transgenic pigs were decreased significantly. The basal levels of the inflammation mediators tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) in transgenic pigs were inhibited markedly compared with the wild-type pigs. Conclusions These results suggest that n-3 PUFAs accumulation in vivo may have beneficial effects on vascular and hfat-1 transgenic pigs may be a useful tool for investigating the involved mechanisms.

To avoid the overheating effect of excitation light and improve the efficacy of photodynamic therapy (PDT) of upconversion nanoplatform, a novel nanoprobe based on 808 nm-excited upconversion nanocomposites (T-UCNPs@Ce6@mSiO2) with low heating effect and deep penetration has been successfully constructed for targeted upconversion luminescence, magnetic resonance imaging (MRI) and high-efficacy PDT in HER2-overexpressed breast cancer. In this nanocomposite, photosensitizers (Ce6) were covalently conjugated inside of mesoporous silica to enhance the PDT efficacy by shortening the distance of fluorescence resonance energy transfer and to decrease the cytotoxicity by preventing the undesired leakage of Ce6. Compared with UCNPs@mSiO2@Ce6, UCNPs@Ce6@mSiO2 greatly promoted the singlet oxygen generation and amplified the PDT efficacy under the excitation of 808 nm laser. Importantly, the designed nanoprobe can greatly improve the uptake of HER2-positive cells and tumors by modifying the site-specific peptide, and the in vivo experiments showed excellent MRI and PDT via intravenous injection by modeling MDA-MB-435 tumor-bearing nude mice. Our strategy may provide an effective solution for overcoming the heating effect and improving the PDT efficacy of upconversion nanoprobes, and has potential application in visualized theranostics of HER2-overexpressed breast cancer.

Tenuigenin (TNG), isolated from the root of the Chinese herb Polygala tenuifolia, possesses various biological and pharmacological activities, including anti-oxidation and anti-inflammation activities. In this study, we aimed to further investigate whether its anti-inflammatory activity is associated with the inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Our results showed that TNG treatment dramatically reduced prostaglandin E2 (PGE2) and NO production, decreased iNOS and COX-2 gene expression, inhibited JNK1/2, ERK1/2, p38 and NF-κB (p65) phosphorylation, and blocked IκBα phosphorylation and degradation. Further studies revealed that TNG dramatically up-regulated heme oxygenase (HO)-1 and nuclear factor erythroid 2-related factor 2 (Nrf2) expression, which was related to the induction of Nrf2 nuclear translocation and decreased Keap1 protein expression. Additionally, treatment with JNK1/2, ERK1/2 or p38 inhibitors had no effect on the TNG-induced HO-1 protein expression. Furthermore, the LPS-induced iNOS and COX-2 expression levels were inhibited by TNG, which was partially reversed by the HO-1-siRNA and HO-1 inhibitors. Together, these results showed that TNG's anti-inflammatory activity is related to the inhibition of iNOS and COX-2 expression via down-regulation of the MAPK and NF-κB, and up-regulation of the Nrf2/HO-1 signaling pathways.

White TiO2 nanoparticles (NPs) have been widely used for cancer photodynamic therapy based on their ultraviolet light-triggered properties. To date, biomedical applications using white TiO2 NPs have been limited, since ultraviolet light is a well-known mutagen and shallow penetration. This work is the first report about hydrogenated black TiO2 (H-TiO2 ) NPs with near infrared absorption explored as photothermal agent for cancer photothermal therapy to circumvent the obstacle of ultraviolet light excitation. Here, it is shown that photothermal effect of H-TiO2 NPs can be attributed to their dramatically enhanced nonradiative recombination. After polyethylene glycol (PEG) coating, H-TiO2 -PEG NPs exhibit high photothermal conversion efficiency of 40.8%, and stable size distribution in serum solution. The toxicity and cancer therapy effect of H-TiO2 -PEG NPs are relative systemically evaluated in vitro and in vivo. The findings herein demonstrate that infrared-irradiated H-TiO2 -PEG NPs exhibit low toxicity, high efficiency as a photothermal agent for cancer therapy, and are promising for further biomedical applications.

Scope ω3-polyunsaturated fatty acids (ω3-PUFAs) have beneficial effects on cardiovascular function, and lipoprotein-associated phospholipase A2 (Lp-PLA2) is associated with the risk of cardiovascular disease. Here, we investigated the effects of ω3-PUFAs on Lp-PLA2 expression in vitro and in vivo and explored the mechanisms involved. Methods and results Human monocyticcells (THP-1) were induced into macrophages in an in vitro model. ω3-PUFAs suppressed Lp-PLA2 expression; the suppression induced by docosahexaenoic acid (DHA) was related to reduced inflammation. Tumor necrosis factor-α (TNF-α) was employed to stimulate the phosphorylation of p38 mitogen-activated protein kinase (MAPK), nuclear factor-κB (NF-κB) p65 and Lp-PLA2 expression in macrophages. The stimulation was inhibited by DHA and the anti-inflammatory drug sodium salicylate. Moreover, the stimulation of Lp-PLA2 expression by TNF-α could be suppressed by NF-κB and MAPK pathway inhibitors. Then, chronic inflammation was induced in an in vivo mouse model, resulting in an increase in Lp-PLA2 expression in peripheral blood mononuclear cells (PBMCs) and arteries. This increase was suppressed by ω3-PUFAs. Inhibition of Lp-PLA2 transcription in PBMCs was also observed in ω3-PUFA-enriched swine. Conclusion Our results demonstrate that the protective effects of ω3-PUFAs against cardiovascular events may be related to the suppression of Lp-PLA2 levels.

cope Resveratrol is a naturally occurring polyphenolic compound with known cardioprotective, anti-inflammatory and antioxidant properties. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is associated with the risk of cardiovascular disease. Here, we investigated the effects of resveratrol on Lp-PLA2 expression in vitro and in vivo and explored the underlying mechanisms. Methods and results Human monocytic cells (THP-1) were induced to differentiate into macrophages for an in vitro experimental model. Resveratrol suppressed Lp-PLA2 expression and reduced inflammation; lipopolysaccharide (LPS, 1 μg/ml), tumor necrosis factor-α (TNF-α, 10 ng/ml) and reactive oxygen species (ROS) were employed to stimulate an increase in Lp-PLA2 expression and ROS levels, and the stimulation was inhibited by resveratrol (50 μM) and other antioxidants. The inhibition of resveratrol was inversed partially by sirtuin 1 (SIRT1) inhibitors (Nicotinamide, 1–10 mM) (P

Background The spike proteins of coronaviruses associate with cellular molecules to mediate infection of their target cells. The characterization of cellular proteins required for virus infection is essential for understanding viral life cycles and may provide cellular targets for antiviral therapies. Results We identified Neural Cell Adhesion Molecule (NCAM) as a novel interacting partner of the PHE-CoV S protein. A T7 phage display cDNA library from N2a cells was constructed, and the library was screened with the soluble PHE-CoV S glycoproteins. We used a coimmunoprecipitation assay to show that only the NCAM was a binding partner of spike protein. We found that a soluble form of anti-NCAM antibody blocked association of the PHE-CoV with N2a cells. Furthermore, double-stranded siRNA targeted against NCAM inhibited PHE-CoV infection. Conclusions A novel interaction was identified between NCAM and spike protein and this association is critical during PHE-CoV infection.

Due to non-invasive deep imaging and therapy, multifunctional agents of magnetic resonance (MR)/upconversion luminescence (UCL) imaging and photodynamic therapy (PDT) play an important role in clinical diagnosis and treatment of cancers, and also in the assessment of therapy effect. In this paper, tetra-sulfonic phthalocyanine aluminium (AlPcS4) photosensitizers-conjugated Fe3O4@NaYF4:Yb/Er (NPs-AlPcS4) nanocomplexes were synthesized for the T2-weighted MR/UCL imaging and PDT of cancer cells. The PEG-coated Fe3O4@NaYF4:Yb/Er nanoparticles (NPs) with a core–shell structure showed strong T2-weighted MR relaxivity (r2 = 42.131 mM−1 s−1) and UCL emission in the visible region (the bands at about 654–674 nm, 545 nm and 524 nm), and were conjugated successfully with AlPcS4 photosensitizer by electrostatic interaction. By direct observation of XFM and staining with Prussian blue, the element distribution and location of NPs in MCF-7 cells were characterized, respectively. Under irradiation from a 980 nm laser, the death ratio of MCF-7 cells incubated with NPs-AlPcS4 nanocomplexes could be up to about 70%. The results indicated that the as-prepared NPs-AlPcS4 nanocomplexes would be a potential candidate as multifunctional nanoprobes for the dual-modal T2-weighted MR/UCL imaging and PDT of cancers in the future.

Multifunctional Fe(3)O(4)-TiO(2) nanocomposites with Janus structure for magnetic resonance imaging (MRI) and potential photodynamic therapy (PDT) were synthesized, in which Fe(3)O(4) was used as a MRI contrast agent and TiO(2) as an inorganic photosensitizer for PDT. Their morphology, structure, and MRI and PDT performance were characterized, respectively. Moreover, the location of Fe(3)O(4)-TiO(2) nanocomposites in MCF-7 cells was also investigated by the staining of Prussian blue and alizarin red, respectively. The results showed that the as-prepared Fe(3)O(4)-TiO(2) nanocomposites had good T(2)-weighted MRI performance, and the MCF-7 cells incubated with nanocomposites could be killed under the irradiation of UV light. Compared with traditional organic photosensitizers, TiO(2) inorganic photosensitizers could have more stable PDT performance due to their nanoscale size and anti-photodegradable stability. Therefore, the as-prepared Fe(3)O(4)-TiO(2) nanocomposites could have potential applications as a new kind of multifunctional agent for both MRI and PDT.

In order to overcome the multidrug resistance of breast cancer cells, doxorubicin was loaded onto TiO2 nanoparticles in which the electrostatic interactions hold the drug and the nanoparticles together. The anticancer activity of this nanocomposite was evaluated in multidrug resistant breast cancer cells. In nanocomposite treated MCF-7/ADM cells, drug accumulation increased with enhanced anticancer activity about 2.4 times compared to that of doxorubicin alone. The potential mechanism of enhanced drug accumulation is ascribed to the fact that the nanocomposite directly transports the drugs into cells via internalization, bypassing the P-glycoprotein mediated doxorubicin pumping system. Our results reinforce that the nanocomposite, as a pH controlled drug release system, could be used to overcome multidrug resistance of human breast cancer cells.

Using an improved hydrolysis method of inorganic salts assisted with water-bath incubation, ultrasmall water-soluble metal-iron oxide nanoparticles (including Fe(3)O(4), ZnFe(2)O(4) and NiFe(2)O(4) nanoparticles) were synthesized in aqueous solutions, which were used as T(1)-weighted contrast agents for magnetic resonance imaging (MRI). The morphology, structure, MRI relaxation properties and cytotoxicity of the as-prepared metal-iron oxide nanoparticles were characterized, respectively. The results showed that the average sizes of nanoparticles were about 4 nm, 4 nm and 5 nm for Fe(3)O(4), ZnFe(2)O(4) and NiFe(2)O(4) nanoparticles, respectively. Moreover, the nanoparticles have good water dispersibility and low cytotoxicity. The MRI test showed the strong T(1)-weighted, but the weak T(2)-weighted MRI performance of metal-iron oxide nanoparticles. The high T(1)-weighted MRI performance can be attributed to the ultrasmall size of metal-iron oxide nanoparticles. Therefore, the as-prepared metal-iron oxide nanoparticles with good water dispersibility and ultrasmall size can have potential applications as T(1)-weighted contrast agent materials for MRI.