Biocompatibility Assessment of Polyethylene Glycol-Poly L-Lysine-Poly Lactic-Co-Glycolic Acid Nanoparticles In Vitro and In Vivo.

The present study was designed to evaluate the biocompatibility of nanoparticles polyethylene glycol (PEG)-poly L-lysine (PLL)-poly lactic-co-glycolic acid copolymer (PLGA) (PEG-PLL-PLGA) before clinical application. We applied some tests to assess the safety of PEG-PLL-PLGA nanoparticles (NPs). There was low cytotoxicity of PEG-PLL-PLGA NPs in vitro as detected by MTT assay. Cell apoptosis and intracellular accumulation of PEG-PLL-PLGA were determined by FCM assay. The apoptotic rate induced by nanoparticles and the fluorescence intensity of intracellular daunorubicin (DNR) demonstrated that DNR-PEG-PLL-PLGA could be taken up by the mouse fibroblast cells (L929 cells). Hemolysis test and micronucleus (MN) assay demonstrated that the nanoparticles have no obviously blood toxicity and genotoxicity. DNR-PEG-PLL-PLGA NPs were injected into mice through tail vein to calculate the median lethal dose (LD50), the results showed that they had a wide safe scale. Blood was taken by removing the eyeball of mice to study the influence of DNR-PEG-PLL-PLGA in hepatic and renal functions. The results revealed that there was no significant difference as compared with the control group. Interestingly, the pathologic changes of heart, liver, spleen, lung and kidney were observed in nanoparticles treated mice. Thus, this study demonstrates that PEG-PLL-PLGA NPs appear to be highly biocompatible and safe nanoparticles that can be suitable for further application in the treatment of tumor.

Applications of daunorubicin-loaded PLGA-PLL-PEG-Tf nanoparticles in hematologic malignancies: an in vitro and in vivo evaluation.

BACKGROUND: With the development of drug delivery, novel tools and technological approaches have captured the attention of researchers in recent years. Several target drug delivery systems (DDSs) including nanoparticles (NPs) have been developed as an important strategy to deliver classical medicine. OBJECTIVE: The objective of this study was to evaluate the application of novel daunorubicin (DNR)-loaded poly(lactic-co-glycolic acid)-poly-l-lysine-polyethylene glycol-transferrin (Tf) nanoparticles (DNR-loaded NPs) in hematologic malignancies in vitro and in vivo. MATERIALS AND METHODS: DNR-loaded NPs were prepared by the modified double-emulsion solvent evaporation/diffusion method, and its microscopic form was observed under scanning electron microscope. Intracellular distribution of DNR was directly detected by fluorescence microscopy. After establishment of a tumor xenograft model by injecting K562 cells into the left leg of nude mice, the therapeutic effect of the DNR-loaded NPs on the growth of tumors was measured by calculating the tumor size, and the relative expression of Caspase-3 protein was detected by immunohistochemical staining. Furthermore, intracellular concentration of DNR and the extent of cell apoptosis in primary leukemia cells were quantified by flow cytometry. RESULTS: DNR-loaded NPs had a spherical shape of about 180 nm in diameter. DNR-loaded NP group showed a significant enhancement of cellular uptake in K562 cells compared with DNR group. Tumor inhibition rate was higher in DNR-loaded NP group in comparison with DNR group, and the relative expression of Caspase-3 protein was upregulated in DNR-loaded NP group compared with DNR group. Furthermore, DNR-loaded NPs obviously increased intracellular concentration of DNR in primary leukemia cells compared with DNR group, but there was no significant difference in primary cell apoptosis between the two groups. These findings suggest that the novel NP DDS can enhance the performance of conventional antitumor drugs and may be suitable for further application in the treatment of hematologic malignancies.

Aptamer-based hydrogel barcodes for the capture and detection of multiple types of pathogenic bacteria.

Rapid and sensitive diagnosing hematological infections based on the separation and detection of pathogenic bacteria in the patient's blood is a significant challenge. To address this, we herein present a new barcodes technology that can simultaneously capture and detect multiple types of pathogenic bacteria from a complex sample. The barcodes are poly (ethylene glycol) (PEG) hydrogel inverse opal particles with characteristic reflection peak codes that remain stable during bacteria capture on their surfaces. As the spherical surface of the particles has ordered porous nanostructure, the barcodes can provide not only more surface area for probe immobilization and reaction, but also a nanopatterned platform for highly efficient bioreactions. In addition, the PEG hydrogel scaffold could decrease the non-specificity adsorption by its anti-adhesive effect, and the decorated aptamer probes in the scaffolds could increase the sensitivity, reliability, and specificity of the bacteria capture and detection. Moreover, the tagged magnetic nanoparticles in the PEG scaffold could impart the barcodes with controllable movement under magnetic fields, which can be used to significantly increase the reaction speed and simplify the processing of the bioassays. Based on the describe barcodes, it was demonstrated that the bacteria could be captured and identified even at low bacterial concentrations (100 CFU mL-1) within 2.5h, which is effectively shortened in comparison with the "gold standard" in clinic. These features make the barcodes ideal for capturing and detecting multiple bacteria from clinical samples for hematological infection diagnostics.

The application of Fe3O4 nanoparticles in cancer research: a new strategy to inhibit drug resistance.

Although much effort has been extended to the efficient cancer therapies, the drug resistance is still a major obstacle in cancer chemotherapeutic treatments. Almost 90% of the cancer therapy failure is caused by the relative problems. Recently, the application of drug coated polymer nanospheres and nanoparticles to inhibit the related drug resistance has attracted much attention. In this report, we have explored a novel strategy to inhibit the multidrug resistance of the targeted tumor cells by combining the unique properties of tetraheptylammonium capped Fe(3)O(4) magnetic nanoparticles with the drug accumulation of anticancer drug daunorubicin. Our results of confocal fluorescence and atomic force microscopy (AFM) as well as electrochemical studies demonstrate the remarkable synergistic effect of Fe(3)O(4) nanoparticles on drug uptake of daunorubicin in leukemia K562 cells. These observations indicate that the interaction between the magnetic nanoparticles Fe(3)O(4) and biologically active molecules on the membrane of leukemia cell lines may contribute to their beneficial effect on cellular uptake so that the synergistic enhanced effect of magnetic nanoparticles Fe(3)O(4) on drug uptake of drug resistance leukemia K562 cells could be observed upon application of the Fe(3)O(4) nanoparticles.

Effects of major parameters of nanoparticles on their physical and chemical properties and recent application of nanodrug delivery system in targeted chemotherapy.

Chemotherapy is still one of the main cancer therapy treatments, but the curative effect of chemotherapy is relatively low, as such the development of a new cancer treatment is highly desirable. The gradual maturation of nanotechnology provides an innovative perspective not only for cancer therapy but also for many other applications. There are a diverse variety of nanoparticles available, and choosing the appropriate carriers according to the demand is the key issue. The performance of nanoparticles is affected by many parameters, mainly size, shape, surface charge, and toxicity. Using nanoparticles as the carriers to realize passive targeting and active targeting can improve the efficacy of chemotherapy drugs significantly, reduce the mortality rate of cancer patients, and improve the quality of life of patients. In recent years, there has been extensive research on nanocarriers. In this review, the effects of several major parameters of nanoparticles on their physical and chemical properties are reviewed, and then the recent progress in the application of several commonly used nanoparticles is presented.

Hybrid hydrogel photonic barcodes for multiplex detection of tumor markers.

Barcodes-based suspension array have for demonstrated values in multiplex assay of tumor markers. Photonic barcodes which are encoded by their characteristic reflection peaks are the important supports for suspension array due to their stable code, low fluorescent background and high surface-volume ratio. Attempts to develop this technology tend to improve the function of the photonic barcodes. Here, we present a new type of hybrid hydrogel photonic barcodes for efficient multiplex assays. This photonic barcodes are hybrid inverse opal hydrogel composed of poly(ethylene glycol) diacrylate (PEG-DA) and agarose. The polymerized PEG-DA hydrogel could guarantee the stabilities of the inverse opal structure and its resultant code, while the agarose could offer active chemical groups for the probe immobilization and homogeneous water surrounding for the bioassay. In addition, the interconnected pores inverse opal structure could provide channels for biomolecules diffusing and reaction into the voids of barcodes. These features imparted the hybrid hydrogel photonic barcodes with limits of detection (LOD) of 0.78ng/mL for carcinoembryonic antigen (CEA) and 0.21ng/mL for α-fetoprotein (AFP), respectively. It was also demonstrated that the proposed barcodes showed acceptable accuracy and detection reproducibility, and the results were in acceptable agreement with those from common clinic method for the detections of practical clinical samples. Thus, our technique provides a new platform for simultaneous multiplex immunoassay.

Curcumin-coordinated nanoparticles with improved stability for reactive oxygen species-responsive drug delivery in lung cancer therapy.

BACKGROUND: The natural compound curcumin (Cur) can regulate growth inhibition and apoptosis in various cancer cell lines, although its clinical applications are restricted by extreme water insolubility and instability. To overcome these hurdles, we fabricated a Cur-coordinated reactive oxygen species (ROS)-responsive nanoparticle using the interaction between boronic acid and Cur. MATERIALS AND METHODS: We synthesized a highly biocompatible 4-(hydroxymethyl) phenylboronic acid (HPBA)-modified poly(ethylene glycol) (PEG)-grafted poly(acrylic acid) polymer (PPH) and fabricated a Cur-coordinated ROS-responsive nanoparticle (denoted by PPHC) based on the interaction between boronic acid and Cur. The mean diameter of the Cur-coordinated PPHC nanoparticle was 163.8 nm and its zeta potential was -0.31 mV. The Cur-coordinated PPHC nanoparticle improved Cur stability in physiological environment and could timely release Cur in response to hydrogen peroxide (H2O2). PPHC nanoparticles demonstrated potent antiproliferative effect in vitro in A549 cancer cells. Furthermore, the viability of cells treated with PPHC nanoparticles was significantly increased in the presence of N-acetyl-cysteine (NAC), which blocks Cur release through ROS inhibition. Simultaneously, the ROS level measured in A549 cells after incubation with PPHC nanoparticles exhibited an obvious downregulation, which further proved that ROS depression indeed influenced the therapeutic effect of Cur in PPHC nanoparticles. Moreover, pretreatment with phosphate-buffered saline (PBS) significantly impaired the cytotoxic effect of Cur in A549 cells in vitro while causing less damage to the activity of Cur in PPHC nanoparticle. CONCLUSION: The Cur-coordinated nanoparticles developed in this study improved Cur stability, which could further release Cur in a ROS-dependent manner in cancer cells.

The in vitro inhibition of multidrug resistance by combined nanoparticulate titanium dioxide and UV irradition.

The appearance of drug-resistant (especially, multidrug-resistant (MDR)) tumor cells is a major obstacle to the success of chemotherapy; thus, the development of effective anti-MDR agents plays an important role in the tumor therapy. In this report, the considerable effect of nano-TiO2 and UV illumination on the drug resistance of target cancer cells has been explored, and the fresh evidence from the fluorescence spectroscopy and microscopy as well as electrochemical studies demonstrates the significant enhancement effect of nano-TiO2 to the drug uptake by drug-resistant leukemia cells. Besides, it is also observed that the combination of the nano-TiO2 and UV irradiation with the accompanying anticancer drug daunorubicin could provoke some considerable changes of the cell membrane of the target leukemia cells, which indicates that nano-TiO2 could not only increase the drug accumulation in target cancer cells, but also act as an effective anti-MDR agent to inhibit the relative drug resistance.

PK11195-chitosan-graft-polyethylenimine-modified SPION as a mitochondria-targeting gene carrier.

Superparamagnetic iron oxide nanoparticle (SPION) holds great potential as a gene delivery system due to its unique properties, such as good biocompatibility and non-invasive targeting ability. In this study, we modified SPION with chitosan-graft-PEI (CHI-g-PEI) and PK11195, to fabricate a mitochondria-targeting gene carrier, PK-CP-SPION. PK-CP-SPION manifested prominent physicochemical properties for magnetic guided gene delivery, and it could effectively condense and protect DNA at proper weight ratios. The in vitro cytotoxicity of PK-CP-SPIONs was mild. Under an external magnetic field, the transfection efficiency of PK-CP-SPIONs was comparable to PEI 25 K with shorter transfection time. PK11195 facilitated the specific accumulation of PK-CP-SPIONs in mitochondria, leading to the leakage of cytochrome c, the dissipation of mitochondrial membrane potential and subsequently the activation of mitochondria apoptosis pathway. These results indicated that with further development, PK-CP-SPIONs could serve as a multifunctional nanoplatform for magnetic targeting gene delivery and mitochondria-targeting therapy, leading enhanced therapeutic effect towards tumor cells.

Targeted multidrug-resistance reversal in tumor based on PEG-PLL-PLGA polymer nano drug delivery system.

The study investigated the reversal of multidrug resistance (MDR) and the biodistribution of nanoparticles (NPs) that target leukemia cells in a nude mice model via a surface-bound transferrin (Tf). The cytotoxic cargo of daunorubicin (DNR) and tetrandrine (Tet) was protected in the NPs by an outer coat composed of polyethylene glycol (PEG)-poly-L-lysine (PLL)-poly(lactic-co-glycolic acid) (PLGA) NPs. Injection of DNR-Tet-Tf-PEG-PLL-PLGA NPs into nude mice bearing MDR leukemia cell K562/A02 xenografts was shown to inhibit tumor growth, and contemporaneous immunohistochemical analysis of tumor tissue showed the targeted NPs induced apoptosis in tumor cells. Targeted tumor cells exhibited a marked increase in Tf receptor expression, with noticeable decreases in P-glycoprotein, MDR protein, and nuclear factor κB, as assessed by quantitative real-time polymerase chain reaction and Western blot analysis. Moreover, the concentration of DNR was shown to increase in plasma, tumor tissue, and major organs. Flow cytometry analysis with a near-infrared fluorescent (NIRF) dye, NIR797, was used to study the effectiveness of Tf as a targeting group for leukemia cells, a finding that was supported by NIRF imaging in tumor-bearing nude mice. In summary, our studies show that DNR-Tet-Tf-PEG-PLL-PLGA NPs provide a specific and effective means to target cytotoxic drugs to MDR tumor cells.

Synthesis and characterization of tumor-targeted copolymer nanocarrier modified by transferrin.

To increase the encapsulation of hydrophilic antitumor agent daunorubicin (DNR) and multidrug resistance reversal agent tetrandrine (Tet) in the drug delivery system of nano-particles (NPs), a functional copolymer NP composed of poly(lactic-co-glycolic acid) (PLGA), poly-L-lysine (PLL), and polyethylene glycol (PEG) was synthesized and then loaded with DNR and Tet simultaneously to construct DNR/Tet-PLGA-PLL-PEG-NPs using a modified double-emulsion solvent evaporation/diffusion method. And to increase the targeted antitumor effect, DNR/Tet-PLGA-PLL-PEG-NPs were further modified with transferrin (Tf) due to its specific binding to Tf receptors (TfR), which is highly expressed on the surface of tumor cells. In this study, the influence of the diversity of formulation parameters was investigated systematically, such as drug loading, mean particle size, molecular weight, the concentration of PLGA-PLL-PEG-Tf, volume ratio of acetone to dichloromethane, the concentration of polyvinyl alcohol (PVA) in the external aqueous phase, the volume ratio of the internal aqueous phase to the external aqueous phase, and the type of surfactants in the internal aqueous phase. Meanwhile, its possible effect on cell viability was evaluated. Our results showed that the regular spherical DNR/Tet-PLGA-PLL-PEG-Tf-NPs with a smooth surface, a relatively low polydispersity index, and a diameter of 213.0±12.0 nm could be produced. The encapsulation efficiency was 70.23%±1.91% for DNR and 86.5%±0.70% for Tet, the moderate drug loading was 3.63%±0.15% for DNR and 4.27%±0.13% for Tet. Notably, the accumulated release of DNR and Tet could be sustained over 1 week, and the Tf content was 2.18%±0.04%. In cell viability tests, DNR/Tet-PLGA-PLL-PEG-Tf-NPs could inhibit the proliferation of K562/ADR cells in a dose-dependent manner, and the half maximal inhibitory concentration value (total drug) of DNR/Tet-PLGA-PLL-PEG-Tf-NPs was lower than that of DNR, a mixture of DNR and Tet, and DNR/Tet-PLGA-PLL-PEG-NPs. These results clearly indicate that the PLGA-PLL-PEG formulation is a potential drug delivery system for hydrophilic and hydrophobic drugs, and that Tf modification may increase its targeting properties.

PLGA-PLL-PEG-Tf-based targeted nanoparticles drug delivery system enhance antitumor efficacy via intrinsic apoptosis pathway.

Chemotherapy offers a systemic cancer treatment; however, it is limited in clinical administration due to its serious side effects. In cancer medicine, the use of nanoparticles (NPs) drug delivery system (DDS) can sustainedly release anticancer drug at the specific site and reduce the incidence of toxicity in normal tissues. In the present study, we aimed to evaluate the benefit of a novel chemotherapeutic DDS and its underlying mechanisms. Daunorubicin (DNR) was loaded into poly (lactic-co-glycolic acid) (PLGA)-poly-L-lysine (PLL)-polyethylene glycol (PEG)-transferrin (Tf) NPs to construct DNR-PLGA-PLL-PEG-Tf-NPs (DNR-loaded NPs) as a DDS. After incubating with PLGA-PLL-PEG-Tf-NPs, DNR, and DNR-loaded NPs, the leukemia K562 cells were collected and the intracellular concentration of DNR was detected by flow cytometry, respectively. Furthermore, the effect of drugs on the growth of tumors in K562 xenografts was observed and the relevant toxicity of therapeutic drugs on organs was investigated in vivo. Meanwhile, cell apoptosis in the excised xenografts was measured by transferase-mediated dUTP nick-end labeling assay, and the expression of apoptosis-related proteins, including Bcl-2, Bax, Caspase-9, Caspase-3, and cleaved-PARP, was determined by Western blotting analysis. Results showed that DNR-loaded NPs increased intracellular concentration of DNR in K562 cells in vitro and induced a remarkable improvement in anticancer activity in the xenografts in vivo. The expression of Bcl-2 protein was downregulated and that of Bax, Caspase-9, Caspase-3, and cleaved-PARP proteins were obviously upregulated in the DNR-loaded NPs group than that in other ones. Interestingly, pathological assessment showed no apparent damage to the main organs. In summary, the results obtained from this study showed that the novel NPs DDS could improve the efficacy of DNR in the treatment of leukemia and induce apoptosis via intrinsic pathway. Thus, it can be inferred that the new drug delivery may be a useful clinical tool.

A solid-state electrochemiluminescence sensing platform for detection of catechol based on novel luminescent composite nanofibers.

A solid-state electrochemiluminescence (ECL) sensing platform based on the novel luminescent composite nanofibers for detection of catechol has been developed. The carboxylated multi-walled carbon nanotubes (MWNTs) and ruthenium(II) tris-(bipyridine) (Ru(bpy)3(2+)) doped nylon 6 (PA6) luminescent composite nanofibers (Ru-MWNTs-PA6) were successfully fabricated by a one-step electrospinning technique. The Ru-MWNTs-PA6 nanofibers, with unique 3D nanostructure, large specific surface area and a larger amount of immobilized-Ru(bpy)3(2+), maintained the photoelectric properties of the Ru(bpy)3(2+) ions and exhibited excellent ECL behaviors on glassy carbon (GC) electrode. As a solid-state ECL sensing platform, the Ru-MWNTs-PA6 nanofibers can sensitively detect low concentration catechol by monitoring the phenol-dependent ECL intensity change. The detection limit for catechol is 1.0 nM, which is comparable or better than that in the reported assays. The solid-state ECL sensor displayed wide linear range, high sensitivity and good stability. It holds promise for the electrospun nanofibers-based ECL sensors have a great potential for routine analyses.

Handy, rapid and multiplex detection of tumor markers based on encoded silica-hydrogel hybrid beads array chip.

Malignant tumor has become the leading cause of death worldwide; however, multiplex detection technology could provide great assistance in large-scale population screening of diseases which could effectively reduce the mortality of malignant tumors. Here a microbeads array chip, which could be a perfect alternative method for the early screening, was developed. Silica-hydrogel hybrid bead (SHHB) with photonic encoding, which consists of both silica and hydrogel materials, was manufactured as the carrier of microbeads array for the first time. The SHHB has the advantages of the beads made of silica or hydrogel, but does not have their limitations. Reaction conditions of SHHBs array were optimized and then the fluorescent concentration curves of two widely-used tumor markers, human alpha fetoprotein and carcinoembryonic antigen, were constructed. The accuracy of SHHBs array has been proven according to the comparison between the results obtained by detecting 50 clinical samples with SHHBs array and chemiluminescence immunoassay. A cassette like chip device has also been developed to standardize operational processes and benefit automization in the next work. Hence it is concluded that SHHBs array chip is a handy, rapid and multiplex immunoassay technology, which could imply its practical application in clinical immunoassay in the near future.

Synthesis and antitumor efficacy of daunorubicin-loaded magnetic nanoparticles.

BACKGROUND: A promising approach to optimize the disposition of daunorubicin-loaded magnetic nanoparticles (DNR-MNPs) was developed to minimize serious side effects of systematic chemotherapy for cancer. METHODS: The physical properties of DNR-MNPs were investigated and their effect on leukemia cells in vitro was evaluated by a standard WST-1 cell proliferation assay. Furthermore, cell apoptosis and intracellular accumulation of DNR were determined by FACSCalibur flow cytometry. RESULTS: Our results showed that the majority of MNPs were spherical and their sizes were from 10 to 20 nm. The average hydrodynamic diameter of DNR-MNPs in water was 94 nm. The in vitro release data showed that the DNR-MNPs have excellent sustained release property. Proliferation of K562 cells was inhibited in a dose-dependent manner by DNR in solution (DNR-Sol) or by DNR-MNPs. The IC(50) for DNR-MNPs was slightly higher than that for DNR-Sol. DNR-MNPs also induced less apoptosis in K562 cells than did DNR-Sol. Detection of fluorescence intensity of intracellular DNR demonstrated that DNR-MNPs could be taken up by K562 cells and persistently released DNR in cells. CONCLUSION: Our study suggests that optimized DNR-MNPs formulation possesses sustained drug-release and favorable antitumor properties, which may be used as a conventional dosage form for antitumor therapy.

Reversion of multidrug resistance in tumor by biocompatible nanomaterials.

In this review we have focused on the utilization of the biocompatible nanomaterials to reverse multidrug resistance (MDR), a major clinical obstacle in cancer therapeutics. Based on the comprehension of the mechanism of MDR and common reversal methods, the strategies and key properties of anti-MDR nanomaterials are explored and described to show how these features could provide the potential therapeutic effects that are not achievable with other modalities. The use of biocompatible nanoparticles with different designs and therapeutic approaches to reverse the MDR of cancer chemotherapeutics offers promising opportunities to benefit patients in the future.

Biocompatibility of Fe3O4/DNR magnetic nanoparticles in the treatment of hematologic malignancies.

PURPOSE: The objectives of this research were to assess the biocompatibility of self-assembled Fe(3)O(4) magnetic nanoparticles (MNPs) loaded with daunorubicin (DNR), ie, (Fe(3)O(4)-MNPs/DNR), and to explore their potential application in the treatment of hematologic malignancies. METHODS: A hemolysis test was carried out to estimate the hematologic toxicity of Fe(3)O(4)- MNPs/DNR and a micronucleus assay was undertaken to identify its genotoxicity. Fe(3)O(4)-MNPs/ DNR were injected intraperitoneally into mice to calculate the median lethal dose (LD(50)). The general condition of the mice was recorded, along with testing for acute toxicity to the liver and kidneys. RESULTS: Hemolysis rates were 2.908%, 2.530%, and 2.415% after treatment with different concentrations of Fe(3)O(4)-MNPs/DNR. In the micronucleus assay, there was no significant difference in micronucleus formation rate between the experimental Fe(3)O(4)-MNPs/DNR groups and negative controls (P > 0.05), but there was a significant difference between the experimental groups and the positive controls (P < 0.05). The LD(50) of the Fe(3)O(4)-MNPs/DNR was 1009.71 mg/kg and the 95% confidence interval (CI) was 769.11-1262.40 mg/kg, while that of the DNR groups was 8.51 mg/kg (95% CI: 6.48-10.37 mg/kg), suggesting that these nanoparticles have a wide safety margin. Acute toxicity testing showed no significant difference in body weight between the treatment groups at 24, 48, and 72 hours after intraperitoneal injection. The mice were all in good condition, with normal consumption of water and food, and their stools were formed and yellowish-brown. Interestingly, no toxic reactions, including instability of gait, convulsion, paralysis, and respiratory depression, were observed. Furthermore, alanine transaminase, blood urea nitrogen, and creatinine clearance in the experimental Fe(3)O(4)-MNPs/ DNR groups were 66.0 ± 28.55 U/L, 9.06 ± 1.05 mmol/L, and 18.03 ± 1.84 µmol/L, respectively, which was not significantly different compared with the control and isodose DNR groups. CONCLUSION: Self-assembled Fe(3)O(4)-MNPs/DNR appear to be highly biocompatible and safe nanoparticles, and may be suitable for further application in the treatment of hematologic malignancies.

Study on the enhanced cellular uptake effect of daunorubicin on leukemia cells mediated via functionalized nickel nanoparticles.

The success of cancer chemotherapy is largely dependent on the efficient anticancer drug accumulation in target tumor tissues and cells so as to inhibit the proliferation of the cancer cells. Recently, some biocompatible nanomaterials have been utilized as drug target delivery systems and have shown the great potential to effectively afford the sustained drug delivery for the target cancer cells. In this study, we have explored the possibility for the bio-application of the functionalized nickel (Ni) nanoparticles and the efficiency of the functionalized Ni nanoparticles on drug permeability, and cellular uptake of leukemia K562 cells in vitro has been probed via atomic force microscopy, inverted fluorescence microscopy and confocal microscopy, electrochemical study and MTT (3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyl-tetrazolium bromide) assay. It is observed that the presence of relevant Ni nanoparticles could induce the membrane structure change of target cells and efficiently improve the permeability of the cell membrane so that the combination of these Ni nanoparticles with anticancer drug daunorubicin could have a synergistic effect on the efficient cytotoxicity suppression in leukemia cancer cells. These observations indicate the great potential of Ni nanoparticles in the future biomedical application including target cancer diagnosis and chemotherapy.

Novel nanocomposite of nano fe(3)o(4) and polylactide nanofibers for application in drug uptake and induction of cell death of leukemia cancer cells.

Novel nanocomposites of polylactide (PLA) nanofibers and tetraheptylammonium-capped Fe3O4 magnetic nanoparticles have been prepared and utilized to realize the efficient accumulation of anticancer drug daunorubicin in target cancer cells. The observations of optical microscopy and confocal fluorescence microscopy indicate that the PLA nanofibers and Fe3O4 nanoparticles may contribute to their beneficial effects on intracellular drug uptake of leukemia K562 cell lines in which the efficiently enhanced accumulation of anticancer drug daunorubicin on the membrane of cancer cells could be observed. Meanwhile, the electrochemical detection and the microculture tetrazolium studies were also explored to probe the effect of the relevant nanomaterials on the drug uptake of cancer cells. The results illustrate that the nanocomposites could effectively facilitate the interaction of daunorubicin with leukemia cells and remarkably enhance the permeation and drug uptake of anticancer agents in the cancer cells, which could readily lead to the induction of the cell death of leukemia cells. This observation suggests a new perspective for the targeted therapeutic approaches of cancers.

Poly(lactic acid) (PLA) based nanocomposites--a novel way of drug-releasing.

In this communication, poly(lactic acid) nanofibers have been fabricated by electrospinning and then poly(lactic acid) (PLA) based nanocomposites have been prepared by accumulating anticancer drug daunorubicin on PLA nanofibers combined with TiO2 nanoparticles. Our atomic force microscopy (AFM) and laser-scanning confocal microscope (LSCM) studies demonstrate that the respective drug molecules could be readily self-assembled on the surface of the blends of nano-TiO2 with PLA polymer nanocomposites, which could further efficiently facilitate the drug permeation and accumulation on the target leukemia K562 cells. Besides, the respective new nanocomposites have good biocompatibility, ease of surface chemistry modification and very high surface area, which may afford the possibility for their promising application in pharmacology and biomedical engineering areas.