Albumin Nanospheres Research Articles

Ultrasmall Au/Pt-loaded biocompatible albumin nanospheres to enhance photodynamic/catalytic therapy via triple amplification of glucose-oxidase/catalase/peroxidase

The weak catalytic activity of nanocatalysts and the insufficient endogenous hydrogen peroxide (H2O2) in tumor microenvironment (TME) seriously restricted the efficacy of catalytic therapy, and the non-degradability of inorganic nanocarriers was also unfavorable for their clinical applications. Herein, by depositing gold nanoparticles (AuNPs) and platinum nanoparticles (PtNPs) with ultrasmall size and modifying photosensitizer (IR808), a biocompatible bovine serum albumin (BSA) nanoplatform (BSA@Au/Pt-IR808) with triple-amplification of enzyme activity was constructed to enhance photodynamic therapy (PDT) and catalytic therapy. Ultrasmall AuNPs possessed glucose oxidase (GOx)-like activity, by which the self-supplying H2O2 accelerated the dual-enzyme activity of peroxidase (POD) and catalase (CAT) of ultrasmall PtNPs, promoting the generation of hydroxyl radical (·OH) and singlet oxygen (1O2). Compared with BSA-IR808 and BSA@Pt, the yields of 1O2 and ·OH of BSA@Au/Pt-IR808 increased by 38.2% and 18.6%. Under the combination action of photothermal therapy (PTT)/PDT/catalytic therapy of BSA@Au/Pt-IR808, the cell viability significantly reduced to 12.8%, and the tumors were completely eliminated, demonstrating the enhanced PDT and catalytic therapy against breast cancer.

Self-assembled albumin nanoparticles induce pyroptosis for photodynamic/photothermal/immuno synergistic therapies in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is characterized by a high degree of malignancy, early metastasis, limited treatment, and poor prognosis. Immunotherapy, as a new and most promising treatment for cancer, has limited efficacy in TNBC because of the immunosuppressive tumor microenvironment (TME). Inducing pyroptosis and activating the cyclic guanosine monophosphate-adenosine monophosphate synthase/interferon gene stimulator (cGAS/STING) signaling pathway to upregulate innate immunity have become an emerging strategy for enhancing tumor immunotherapy. In this study, albumin nanospheres were constructed with photosensitizer-IR780 encapsulated in the core and cGAS-STING agonists/H2S producer-ZnS loaded on the shell (named IR780-ZnS@HSA). In vitro, IR780-ZnS@HSA produced photothermal therapy (PTT) and photodynamic therapy (PDT) effects. In addition, it stimulated immunogenic cell death (ICD) and activated pyroptosis in tumor cells via the caspase-3-GSDME signaling pathway. IR780-ZnS@HSA also activated the cGAS-STING signaling pathway. The two pathways synergistically boost immune response. In vivo, IR780-ZnS@HSA + laser significantly inhibited tumor growth in 4T1 tumor-bearing mice and triggered an immune response, improving the efficacy of the anti-APD-L1 antibody (aPD-L1). In conclusion, IR780-ZnS@HSA, as a novel inducer of pyroptosis, can significantly inhibit tumor growth and improve the efficacy of aPD-L1.

The therapeutic effect of PEI-Fe3O4/pYr-ads-8-5HRE-cfosp-IFNG albumin nanospheres combined with magnetic fluid hyperthermia on hepatoma.

Hepatocellular carcinoma (HCC) is one of the most prevalent and deadly malignant tumors with serious clinical and socioeconomic consequences. Although gene therapy holds great promise in the treatment of hepatoma, its clinical applications are hindered by uncontrolled gene transmission and transcription. The pY-ads-8-5HRE-cfosp-IFNG plasmid was constructed and identified by double enzyme digestion and gene sequencing. The expression of pYr-ads-8-5HRE-cfosp-IFNG in HepG2 cells was detected by quantitative PCR. PEI-Fe3O4/pYr-ads-8-5HRE-cfosp-IFNG albumin nanospheres were prepared and characterized. In vitro heating test of magnetic albumin nanospheres in an alternating magnetic field (AMF) was carried out. The therapeutic effect of PEI-Fe3O4/pYr-ads-8-5HRE-cfosp-IFNG albumin nanospheres on hepatocellular carcinoma was investigated by cell and animal experiments. After treatment, mice blood was collected for clinical biochemical analysis and histopathological evaluation of major organs was performed to assess potential adverse effects of treatment. Double enzyme digestion and gene sequencing showed that the pY-ads-8-5HRE-cfosp-IFNG plasmid was constructed successfully. QPCR results showed that the IFNγ transcript level in the PEI-Fe3O4/pYr-ads-8-5HRE-cfosp-IFNG group was higher than that in the PEI-Fe3O4/pYr-ads-8-cfosp-IFNG group after being treated with hypoxia (P<0.05). TEM revealed that the self-prepared PEI-Fe3O4/pYr-ads-8-5HRE-cfosp-IFNG albumin nanospheres exhibit an approximately spherical or elliptical shape. The hydrodynamic size of the albumin nanospheres was 139.7 nm. The maximum temperature of 0.25 mg/mL solution is stable at about 44°C, which is suitable for tumor thermal therapy without damaging normal tissues. The relative cell inhibition rate of the radiation-gene therapy and MFH combination group was higher than that of other control groups in CCK8 experiment. (P<0.05) Flow cytometry showed that the apoptosis rate and necrosis rate of the combined treatment group were 42.32% and 35.73%, respectively, higher than those of the other groups. (P<0.05) In animal experiments, the mass and volume inhibition rates of the combined treatment group were 66.67% and 72.53%, respectively, higher than those of other control groups. (P<0.05) Clinical biochemical analysis and histopathological evaluation showed no abnormality. The results indicated the successful construction of the radiation-induced plasmid and demonstrated that the hypoxia enhancer could augment the expression of INFγ in a hypoxia environment. Gene therapy combined with magnetic fluid hyperthermia (MFH) has exhibited excellent outcomes in both cell and animal studies. Our experiments demonstrated that the PEI-Fe3O4/pYr-ads-8-5HRE-cfosp-IFNG albumin nanospheres system is a comprehensive treatment method for hepatoma, which can effectively combine immune genre therapy with hyperthermia.

Bovine Serum Albumin-Encapsulated Ultrasmall Gold Nanoclusters for Photodynamic Therapy of Tumors

Gold nanoclusters (AuNCs) with an ultrasmall size showed potential application in photodynamic therapy (PDT), but short circulation and weak tumor retention restricted their PDT performance. Herein, bovine serum albumin (BSA) nanospheres with good biocompatibility were used to encapsulate AuNCs, by which the stable and biocompatible AuNCs@BSA nanoprobes were synthesized to boost PDT performance. The results showed that ultrasmall AuNCs with a size of 1.5 nm were encapsulated in BSA nanospheres, and the prepared AuNCs@BSA nanoparticles with an average size of 120 nm have high colloid stability and enhanced fluorescence emission. Compared with single AuNCs, AuNCs@BSA possessed higher singlet oxygen yield, which increased from 34.5% to 45.5%. Moreover, AuNCs@BSA showed lower cytotoxicity and stronger cellular uptake, by which the cell viability was reduced to 20.6% and 4T1 tumor completely disappeared, compared with 47.5% cell viability and tumor recurrence of single AuNCs. The results demonstrated that the prepared AuNCs@BSA nanoprobes possessed good biocompatibility and boosted PDT performance and will be potential highly efficient PDT nanoprobes owing to their safety and reliability.

ROS-Mediated Apoptosis Induced by BSA Nanospheres Encapsulated with Fruit Extract of Cucumis prophetarum in Various Human Cancer Cell Lines.

In recent decades, biodegradable polymeric nanoparticles have been used as a nanocarrier for the delivery of anticancer drugs. In the present study, we synthesize bovine serum albumin (BSA) nanospheres and evaluate their ability to incorporate a plant extract with anticancer activity. The plant extract used was the methanol fruit extract of Cucumis prophetarum, which is a medicinal herb. The fruit-extract-encapsulated BSA nanospheres (Cp-BSA nanospheres) were prepared using a desolvation method at various pH values of 5, 7, and 9. The nanosphere formulations were characterized using various techniques such as dynamic light scattering (DLS), ζ-potential, Fourier transform infrared spectroscopy (FTIR), and field-effect scanning electron microscopy (FESEM). The results show that the Cp-BSA nanospheres prepared at pH 7 were spherical with a uniform particle size, low polydispersity index (PDI), ζ-potential, and high entrapment efficiency (82.3%) and showed sustained release of fruit extract from Cp-BSA nanospheres in phosphate-buffered saline (PBS), pH 5. The anticancer activity was evaluated on A549, HepG2, MCF-7 cancer cell lines and HEK 293 normal cell lines. In vitro, antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, intracellular reactive oxygen species (ROS) production, and mitochondrial membrane potential were estimated. An in vitro cellular uptake study was performed using fluorescein isothiocyanate (FITC) dye at a different time of incubation, and DNA fragmentation was observed in a dose-dependent manner. The gene expression level of Bax and the suppression level of Bcl-2 were observed upon the treatment of Cp-BSA nanospheres. Thus, the Cp-BSA nanospheres triggered ROS-dependent mitochondrial apoptosis in different human cancer cell lines when compared to the noncancerous cell lines and could be used as a potential candidate for anticancer agents.

PREPARATION AND IN VITRO EVALUATION OF METOPROLOL-LOADED BOVINE SERUM ALBUMIN NANOPARTICLES

Objective: The aim of the present research was to prepare metoprolol-loaded nanospheres. Metoprolol-loaded bovine albumin nanospheres were prepared by nanoprecipitation method. Metoprolol is beta-1-adrenergic receptor inhibitor specific to cardiac cells, thus producing negative chronotropic and ionotropic effect.&#x0D; Methods: Metoprolol nanospheres were prepared by nanoprecipitation method, using bovine serum albumin as polymer. The prepared nanospheres are evaluated for particle size evaluation, drug entrapment efficiency, and zeta potential. Drug-excipient compatibility was determined using Fourier-transform infrared spectroscopy. In vitro release and solubility of the drug from nanoparticles were determined.&#x0D; Results: The particle size of prepared metoprolol nanospheres was found to be always less than 200 nm. Maximum particle size was found to be 196±2.03 nm of batch 4 nanoparticles. Entrapment efficiency of prepared nanospheres was above 80% and maximum percentage entrapment efficiency was found to be 80.4±0.51%. It was found that the percentage entrapment efficiency and drug release were extended with increase in polymer concentration. Zeta potential of the optimized formulation was found to be −20.4 mV. In vitro drug release studies have shown the prolonged release of 94.5±0.54 up to 10 h. Drug release rate is extended with an increase in polymer concentration.&#x0D; Conclusion: Results have concluded that the albumin nanospheres loaded with metoprolol have reduced the blood pressure within 24 h and the prepared nanospheres are effective compared to other formulations and drug delivery.

Marinobacter sp. Stable Hydrous Titanium Oxide-Functionalized Bovine Serum Albumin Nanospheres for Uranium Capture from Spiked Seawater.

A novel nanospherical hydrous titanium oxide adsorbent (hydrous titanium oxide-immobilized bovine serum albumin nanospheres, HTO-BSA-NSs) was prepared by immobilizing HTOs with a manipulated molecular mass and number of active sites for uranium on the surface of BSA-NSs. The adsorption performances of HTO-BSA-NSs were investigated in spiked natural seawater with extra 8 ppm uranium. The results demonstrated that HTO-BSA-NSs are capable of uranium capture from a complex aqueous matrix with a low uranium concentration. Meanwhile, the microbial stability of HTO-BSA-NSs in sterilized natural seawater with Marinobacter sp. was investigated and observed through an optical microscope and TEM, revealing that the wrapped HTOs could protect the BSA-NSs from the decomposition of microorganisms, and the structure and functional groups of HTO-BSA-NSs remain stable compared with the BSA-NSs. In addition, the uranium adsorption mechanism of HTO-BSA-NSs is mainly recognized as dehydrated complexation, which was concluded from characterization analysis, adsorption model fitting, and theoretical calculations based on density functional theory. The remarkable uranium adsorption performance and microbial stability of HTO-BSA-NSs indicated that they have the potential to be a low-cost and environmentally friendly adsorbent for uranium extraction from complex environments such as seawater or uranium-containing industrial wastewater.

131 I radiolabeled immune albumin nanospheres loaded with doxorubicin for in vivo combinatorial therapy.

For the purpose of providing new insights for high-efficiency radiochemotherapy of hepatoma, a radioimmunotherapy and chemotherapy combinatorial therapy albumin nanospheres 131 I-antiAFPMcAb-DOX-BSA-NPs was designed and prepared. It was obtained in a high radiolabeling yield approximately 65% with the radiochemical purity of over 98%. The transmission electron microscope showed that the nanospheres obtained in good monodispersion with a diameter of approximately 230nm. The doxorubicin (DOX) loading capacity of the DOX-BSA-NPs nanoparticles was determined to be approximately 180μg/mg and 95.79±3.89%. DOX was released gradually in 6days. In vivo tumor-growth inhibition experiments showed that after treating with 131 I-antiAFPMcAb-DOX-BSA-NPs for 14days, the tumor volume decreased more obvious than that of other 2 time points and the control groups. All the results indicated that the radiolabeled immune albumin nanospheres 131 I-antiAFPMcAb-DOX-BSA-NPs could significantly inhibit the hepatoma tumor growth with the strategy of combinatorial radioimmunotherapy and chemotherapy.

Bayberry tannin immobilized bovine serum albumin nanospheres: characterization, irradiation stability and selective removal of uranyl ions from radioactive wastewater

A novel bayberry tannin immobilized BSA–BT-NS adsorbent with excellent adsorption capacity and high selectivity for UO22+.

In vivo MR imaging of folate-receptor expression with the folate-specific nanospheres in a C6 glioblastoma model

Purpose: To assess the ability of magnetic albumin nanospheres conjugated with folate (FA-MAN) to provide FR-specific enhancement of C6 glioblastoma on magnetic resonance (MR) images.Procedures: Active targeting effect of magnetic albumin nanospheres conjugated with folate (FA-MAN) was evaluated based on MR images and histopathological analysis. MR imaging of subcutaneously transplanted C6 glioblastomas was performed after intravenous injection of FA-MAN, non-targeted (magnetic albumin nanospheres, MAN) and FA-inhibited (magnetic albumin nanospheres conjugated with folate plus folate, FA-MAN + FA) agents at designated time points. The T2 relaxation times in tumors were compared among different treatment groups and were correlated with histopathological findings. Prussian blue staining and in vivo toxicology assay were also performed simultaneously.Results: Upon MR imaging in vivo, T2 relaxation time of the tumor sites in the group administrated with FA-MAN (T2 is 49 ms, 46 ms and 45 ms at 24 h, 48 h and 72 h, respectively) has statistical difference compared to those in the groups of MAN (T2 is 56 ms, 56 ms and 61 ms at 24 h, 48 h and 72 h, respectively) and FA-MAN + FA nanospheres (T2 is 56 ms, 57 ms and 56 ms at 24 h, 48 h and 72 h, respectively). Prussian blue-stained results demonstrated that more iron particles accumulated in the tumors of the targeted group than those of the other groups. Toxicology assay showed that no noticeable body weight losses were observed after monitoring 31 days, and the results of routine blood parameters, liver and kidney function biomarkers also demonstrated that the nanoshperes did not influence the respectively physiological index. Besides, no obvious pathological injuries on the major organs were examined.Conclusion: Folate-conjugated magnetic albumin nanospheres were more effective in targeting C6 glioblastoma in vivo.

Multiplexed aptasensor for simultaneous detection of carcinoembryonic antigen and mucin-1 based on metal ion electrochemical labels and Ru(NH3)63+ electronic wires

In this paper, a dual-target electrochemical aptasensor has been developed for simultaneous detection of carcinoembryonic antigen and mucin-1 based on metal ion electrochemical labels and Ru(NH3)63+ electronic wires. When targets are present, the interaction between targets and their respective aptamers leads to the dissociation of double-strand DNA because the targets have higher affinity to its aptamer than the complementary strand. And the qualitative and quantitative analyses of the two targets are realized by the differential pulse voltammetry (DPV) peaks generated by metal ion electrochemical labels. For the effective loading of a large number of metal ions, Au/bovine serum albumin (Au/BSA) nanospheres are employed as carriers to develop Au/BSA–metal ions. After Ru(NH3)63+ complexes are embedded into double-strand DNA to form the electronic wires, the electrical conductivity and the electron transfer of the detection system are greatly improved. The detection limit of the proposed assay was calculated as 3.33fM ranging from 0.01pM to 100nM. Therefore, this novel sensing assay provides a new and sensitive platform for detecting several targets simultaneously in biochemical research and clinical diagnosis.

Study of the combined treatment of lung cancer using gene-loaded immunomagnetic albumin nanospheres in vitro and in vivo.

Combination therapy for lung cancer has garnered widespread attention. Radiation therapy, gene therapy, and molecular targeted therapy for lung cancer have certain effects, but the disadvantages of these treatment methods are evident. Combining these methods can decrease their side effects and increase their curative effects. In this study, we constructed a pYr-ads-8-5HRE-cfosp-iNOS-IFNG plasmid (a gene circuit that can express IFNγ), which is a gene circuit, and used that plasmid together with C225 (cetuximab) to prepare gene-loaded immunomagnetic albumin nanospheres (IMANS). Moreover, we investigated the therapeutic effects of gene-loaded IMANS in combination with radiation therapy on human lung cancer in vitro and in vivo. The results showed that this gene circuit was successively constructed and confirmed that the expression of INFγ was increased due to the gene circuit. Gene-loaded IMANS combined with radiation therapy demonstrated improved results in vitro and in vivo. In conclusion, gene-loaded IMANS enhanced the efficacy of combination therapy, solved problems related to gene transfer, and specifically targeted lung cancer cells.

Hepatoma-Targeted Radionuclide Immune Albumin Nanospheres: (131)I-antiAFPMcAb-GCV-BSA-NPs.

An effective strategy has been developed for synthesis of radionuclide immune albumin nanospheres (131I-antiAFPMcAb-GCV-BSA-NPs). In vitro as well as in vivo targeting of 131I-antiAFPMcAb-GCV-BSA-NPs to AFP-positive hepatoma was examined. In cultured HepG2 cells, the uptake and retention rates of 131I-antiAFPMcAb-GCV-BSA-NPs were remarkably higher than those of 131I alone. As well, the uptake rate and retention ratios of 131I-antiAFPMcAb-GCV-BSA-NPs in AFP-positive HepG2 cells were also significantly higher than those in AFP-negative HEK293 cells. Compared to 131I alone, 131I-antiAFPMcAb-GCV-BSA-NPs were much more easily taken in and retained by hepatoma tissue, with a much higher T/NT. Due to good drug-loading, high encapsulation ratio, and highly selective affinity for AFP-positive tumors, the 131I-antiAFPMcAb-GCV-BSA-NPs are promising for further effective radiation-gene therapy of hepatoma.

The study on the preparation and characterization of gene-loaded immunomagnetic albumin nanospheres and their anti-cell proliferative effect combined with magnetic fluid hyperthermia on GLC-82 cells.

As one of the most common malignant tumors, the clinical and socio-economic consequences of lung cancer are significant. Currently, surgery is the main treatment strategy for this disease, but the survival rates of lung cancer patients are not ideal due to the high recurrence rate of the disease. Therefore, many researchers are exploring new specific therapeutic methods that are highly curative and minimally cytotoxic to healthy tissues. To this end, albumin nanospheres simultaneously were loaded with super-paramagnetic iron oxide nanoparticles (as gene vector and anticancer gene), and plasmid pDONR223-IFNG, and modified with anti-EGFR monoclonal antibody cetuximab as therapy. Targeting agents, namely gene-loaded immunomagnetic albumin nanospheres (cetuximab [C225]-IFNG-IMANS), were prepared for targeted lung carcinoma cells (GLC-82 cell lines). Transmission electron microscopy images showed that the C225-IFNG-IMANS were successfully prepared, and the ability of the nanospheres to target GLC-82 cells in vitro was confirmed by Prussian blue staining, immunofluorescence experiments, and magnetic resonance imaging. Transfection photographs and agarose gel electrophoresis proved that pDONR223-IFNG could be encased in the albumin nanospheres. A Cell Counting Kit-8 assay showed that the combination therapy group had significantly more therapeutic effects on GLC-82 cells than other therapy groups. A flow cytometry assay showed that the apoptotic index of the combined treatment group was 67.68%, whereas the indices of the C225 group, gene therapy group, and magnetic fluid hyperthermia group were 12.2%, 16.34%, and 20.04% respectively. Therefore, the combination of thermal treatment, molecular targeted treatment, and gene treatment synergistically targets GLC-82 cells, and the use of C225-IFNG-IMANS as a gene or drug carrier offers a novel and promising approach for the treatment of lung cancer.

Magnetic albumin immuno-nanospheres as an efficient gene delivery system for a potential use in lung cancer: preparation, in vitro targeting and biological effect analysis

Magnetic albumin immuno-nanospheres (MAINs), simultaneously loaded with super-paramagnetic iron oxide nanoparticles for targeting application and anticancer gene, plasmid-survivin/shRNA (pshRNA) and modified with anti-EGFR monoclonal antibody Cetuximab for targeting and treatment agents, were prepared for targeting lung cancer. Transmission electron microscopy images and transfection photographs, respectively, showed that magnetic nanoparticles and pshRNA were successfully encased in the albumin nanospheres. The release profiles in vitro indicated that nanospheres had an obvious effect of sustained release of pshRNA. The results of slide agglutination test and immunofluorescence analysis demonstrated that the immuno-nanospheres retained the immuno-reactivity of Cetuximab. The MAINs significantly increased adherence and uptake by GLC-82 lung cancer cells over-expressed epidermal growth factor receptor over a magnetic albumin nanospheres (MANs) control. The pshRNA-loaded MAINs formulation was more effective than equimolar doses of free Cetuximab, single magnetic targeting with pshRNA (pshRNA-loaded MANs) or single monoclonal antibody targeting with pshRNA (pshRNA-loaded AINs) in the treatment of GLC-82 lung cancer cells. Collectively, the study indicates that the novel pshRNA-loaded magnetic immuno-nanospheres represent a promising approach for magnetic and monoclonal antibody-dependent gene targeting in lung cancer therapy.

GEM-loaded magnetic albumin nanospheres modified with cetuximab for simultaneous targeting, magnetic resonance imaging, and double-targeted thermochemotherapy of pancreatic cancer cells.

BackgroundTargeted delivery is a promising strategy to improve the diagnostic imaging and therapeutic effect of cancers. In this paper, novel cetuximab (C225)-conjugated, gemcitabine (GEM)-containing magnetic albumin nanospheres (C225-GEM/MANs) were fabricated and applied as a theranostic nanocarrier to conduct simultaneous targeting, magnetic resonance imaging (MRI), and double-targeted thermochemotherapy against pancreatic cancer cells.MethodsFe3O4 nanoparticles (NPs) and GEM co-loaded albumin nanospheres (GEM/MANs) were prepared, and then C225 was further conjugated to synthesize C225-GEM/MANs. Their morphology, mean particle size, GEM encapsulation ratio, specific cell-binding ability, and thermal dynamic profiles were characterized. The effects of discriminating different EGFR-expressing pancreatic cancer cells (AsPC-1 and MIA PaCa-2) and monitoring cellular targeting effects were assessed by targeted MRI. Lastly, the antitumor efficiency of double/C225/magnetic-targeted and nontargeted thermochemotherapy was compared with chemotherapy alone using 3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and flow cytometry (FCM) assay.ResultsWhen treated with targeted nanospheres, AsPC-1 cells showed a significantly less intense MRI T2 signal than MIA PaCa-2 cells, while both cells had similar signal strength when incubated with nontargeted nanospheres. T2 signal intensity was significantly lower when magnetic and C225 targeting were combined, rather than used alone. The inhibitory and apoptotic rates of each thermochemotherapy group were significantly higher than those of the chemotherapy-alone groups. Additionally, both MTT and FCM analysis verified that double-targeted thermochemotherapy had the highest targeted killing efficiency among all groups.ConclusionThe C225-GEM/MANs can distinguish various EGFR-expressing live pancreatic cancer cells, monitor diverse cellular targeting effects using targeted MRI imaging, and efficiently mediate double-targeted thermochemotherapy against pancreatic cancer cells.

Exploring a new SPION-based MRI contrast agent with excellent water-dispersibility, high specificity to cancer cells and strong MR imaging efficacy

Advances in contrast agents have greatly enhanced the sensitivity of magnetic resonance imaging (MRI) technique for early diagnosis of cancer. However, the commercial superparamagnetic iron oxide nanoparticles (SPION)-based contrast agents synthesized by co-precipitation method are not monodisperse with irregular morphologies and ununiform sizes. Other reported SPION-based contrast agents synthesized by solvothermal method or thermal decomposition method are limited by the bad water-dispersibility and low specificity to cancer cells. Herein, we propose a new strategy for exploring SPION-based MRI contrast agents with excellent water-dispersibility and high specificity to cancer cells. The SPION was synthesized by a polyol method and then entrapped into albumin nanospheres (AN). After that, a ligand folic acid (FA) was conjugated onto the surface of the AN to construct a SPION-AN-FA composite. The transmission electron microscope (TEM) and dynamic light scattering (DLS) results indicate that the SPION-AN-FA has a spherical shape, a uniform size and an excellent water-dispersibility (polydispersity index (PDI) <0.05). The results of laser scanning confocal microscope (LSCM) and flow cytometry demonstrate that the SPION-AN-FA nanoparticles are highly specific to MCF-7 and SPC-A-1 cells due to the recognition of ligand FA and folate receptor α (FRα). The r2/r1 value of SPION-AN-FA is around 40, which is much higher than that of Resovist® indicating that our SPION-AN-FA has a stronger T2 shortening effect. The T2-weighted images of MCF-7 cells incubated with SPION-AN-FA are significantly darker than those of MCF-7 cells incubated with AN, indicating that our SPION-AN-FA has a strong MR imaging efficacy. In view of the excellent water-dispersibility, the high specificity to cancer cells and the strong MR imaging efficacy, our SPION-AN-FA can be used as a negative MR contrast agent.

Folate/NIR 797-Conjugated Albumin Magnetic Nanospheres: Synthesis, Characterisation, and In Vitro and In Vivo Targeting Evaluation

A practical and effective strategy for synthesis of Folate-NIR 797-conjugated Magnetic Albumin Nanospheres (FA-NIR 797-MAN) was developed. For this strategy, Magnetic Albumin Nanospheres (MAN), composed of superparamagnetic iron oxide nanoparticles (SPIONs) and bovine serum albumin (BSA), were covalently conjugated with folic acid (FA) ligands to enhance the targeting capability of the particles to folate receptor (FR) over-expressing tumours. Subsequently, a near-infrared (NIR) fluorescent dye NIR 797 was conjugated with FA-conjugated MAN for in vivo fluorescence imaging. The FA-NIR 797-MAN exhibited low toxicity to a human nasopharyngeal epidermal carcinoma cell line (KB cells). Additionally, in vitro and in vivo evaluation of the dynamic behaviour and targeting ability of FA-NIR 797-MAN to KB tumours validated the highly selective affinity of FA-NIR 797-MAN for FR-positive tumours. In summary, the FA-NIR 797-MAN prepared here exhibited great potential for tumour imaging, since the near-infrared fluorescence contrast agents target cells via FR-mediated endocytosis. The high fluorescence intensity together with the targeting effect makes FA-NIR 797-MAN a promising candidate for imaging, monitoring, and early diagnosis of cancer at the molecular and cellular levels.

Preparation of folic acid-conjugated, doxorubicin-loaded, magnetic bovine serum albumin nanospheres and their antitumor effects in vitro and in vivo.

BackgroundThis study aimed to generate targeted folic acid-conjugated, doxorubicin-loaded, magnetic iron oxide bovine serum albumin nanospheres (FA-DOX-BSA MNPs) that lower the side effects and improve the therapeutic effect of antitumor drugs when combined with hyperthermia and targeting therapy. A new nanodrug using magnetic nanospheres for heating and addition of the folate receptor with cancer cell specificity was prepared. The characteristics of these nanospheres and their antitumor effects in nasopharyngeal carcinoma were explored.MethodsFA-DOX-BSA MNPs comprising encapsulated magnetic iron oxide nanoparticles were prepared using a desolvation cross-linking method. Activated folic acid (N-hydroxysuccinimide ester of folic acid) was conjugated to the surface of albumin nanospheres via amino groups.ResultsFolic acid was successfully expressed on the surface of the nanospheres. Electron microscopy revealed that the FA-DOX-BSA MNPs were nearly spherical and uniform in size, with an average diameter of 180 nm. The nanomaterial could deliver doxorubicin at clinically relevant doses with an entrapment efficiency of 80%. An increasing temperature test revealed that incorporation of magnetic iron oxide into nanospheres could achieve a satisfactory heat treatment temperature at a significantly lower dose when placed in a high-frequency alternating magnetic field. FA-DOX-BSA MNPs showed greater inhibition of tumors than in the absence of folic acid in vitro and in vivo. Compared with chemotherapy alone, hyperthermia combined with chemotherapy was more effective against tumor cells.ConclusionFolic acid-conjugated bovine serum albumin nanospheres composed of mixed doxorubicin and magnetic iron oxide cores can enable controlled and targeted delivery of anticancer drugs and may offer a promising alternative to targeted doxorubicin therapy for nasopharyngeal carcinoma.

3D origami electrochemical immunodevice for sensitive point-of-care testing based on dual-signal amplification strategy

A dual signal amplification immunosensing strategy that offers high sensitivity and specificity for the detection of low-abundance biomarkers was designed on a 3D origami electrochemical device. High sensitivity was achieved by using novel Au nanorods modified paper working electrode (AuNRs-PWE) as sensor platform and metal ion-coated Au/bovine serum albumin (Au/BSA) nanospheres as tracing tags. High specificity was further obtained by the simultaneous measurement of two cancer markers on AuNRs-PWE surface using different metal ion-coated Au/BSA tracers. The metal ions could be detected directly through differential pulse voltammetry (DPV) without metal preconcentration, and the distinct voltammetric peaks had a close relationship with each sandwich-type immunoreaction. The position and size of the peaks reflected the identity and level of the corresponding antigen. Integrating the dual-signal amplification strategy, a novel 3D origami electrochemical immunodevice for simultaneous detecting carcinoembryonic antigen (CEA) and cancer antigen 125 (CA125) with linear ranges of over 4 orders of magnitude with detection limits down to 0.08pgmL−1 and 0.06mUmL−1 was successfully developed. This strategy exhibits high sensitivity and specificity with excellent performance in real human serum assay. The AuNRs-PWE and the designed tracer on this immunodevice provided a new platform for low-cost, high-throughput and multiplex immunoassay and point-of-care testing in remote regions, developing or developed countries.