Mechanisms of Drug Resistance and Use of Nanoparticle Delivery to Overcome Resistance in Breast Cancers.

Breast cancer is the leading cancer type diagnosed among women in the world. Unfortunately, drug resistance to current breast cancer chemotherapeutics remains the main challenge for a higher survival rate. The recent progress in the nanoparticle platforms and distinct features of nanoparticles that enhance the efficacy of therapeutic agents, such as improved delivery efficacy, increased intracellular cytotoxicity, and reduced side effects, hold great promise to overcome the observed drug resistance. Currently, multifaceted investigations are probing the resistance mechanisms associated with clinical drugs, and identifying new breast cancer-associated molecular targets that may lead to improved therapeutic approaches with the nanoparticle platforms. Nanoparticle platforms including siRNA, antibody-specific targeting and the role of nanoparticles in cellular processes and their effect on breast cancer were discussed in this article.

An evaluative in vitro investigation of the delivery of cytarabine with RGD decorated solid lipid nanoparticles.

AIM: To synthesise cytarabine-loaded SLNs modified with the RGD peptide as a ligand, suitable for effective cancer therapy. METHODS: SLNs were synthesised by the high shear, hot homogenisation technique. A 2 level 3 factor analysis was used in optimisation. Particle size, zeta potential, poly-dispersion index and surface morphology were measured. Drug encapsulation, drug release, release kinetics, nanoparticle stability and chemical structure were determined. LIVE/DEAD® Fluorescence Assay was used to qualify cytotoxicity and Tryphan Blue assay to quantify. RESULTS: Cyt-SLNs exhibited a size of 161 ± 2.25 nm, a PDI of 0.49 ± 0.15 and a zeta potential of -19.8 mV. Entrapment fell at 88.87 ± 0.02% and release at 83.5 ± 0.95%. The in vitro release kinetics pointed towards a diffusion-based drug release mechanism. SLNs remained stable for 60 d. Cytotoxicity studies revealed that conjugation of the ligand with the RDG peptide resulted in a significant decrease in cell viability in both cell lines. CONCLUSION: Overall, the study suggests that RGD-SLN-cyt can be used for effective cancer therapy.

Biosynthesized ZnO Nanoparticles Using Albizia lebbeck Extract Induced Biochemical and Morphological Alterations in Wistar Rats.

Nano-based particles synthesized via green routes have a particular structure that is useful in biomedical applications as they provide cheap, eco-friendly, and non-toxic nanoparticles. In the present study, we reported the effect of various concentrations of Zinc oxide nanoparticles synthesized using A. lebbeck stem bark extract (ZnO NPsAL) as stabilizing agent on rat biochemical profiles and tissue morphology. Adult Wistar rats weighing 170 ± 5 g were randomly classified into eight groups of five rats each; Group A served as a control fed with normal diet and water. Groups B1, B2, C1, C2, D1, D2, and E were treated with 40 mg/kg and 80 mg/kg of the 0.01, 0.05, and 0.1 M biosynthesized ZnO NPsAL and zinc nitrate daily by the gavage method, respectively. The rats were anesthetized 24 h after the last treatment, blood samples, kidney, heart, and liver tissues were collected for biochemical and histopathological analysis. The rats mean body weight, serum alkaline phosphatase, alanine aminotransferase, creatinine, urea, bilirubin, protein, albumin, globulin, total cholesterol, triacylglycerol, and high-density lipoprotein were significantly altered with an increased concentration of biosynthesized ZnO NPsAL when compared with the control group (p < 0.05; n ≥ 5). Furthermore, histopathological analysis of treated rats' kidney, heart, and liver tissue revealed vascular congestion, tubular necrosis, inflammation, and cytoplasmic vacuolation. Biosynthesized ZnO NPsAL showed significant alteration in biochemical parameters and tissue morphology in rats with increasing concentrations of the nanoparticles.

Optimizing the thermophysical behavior of a novel ternary hybrid nanofluid for energy applications through experimental research.

The continual use of fossil fuel technologies has negatively impacted on the environment and has caused huge health challenges globally. Despite the growth of renewable energy technologies, their efficiency issues have hindered widespread adoption. The use of nanofluids as heat transfer fluids in renewable energy technologies have further improved their overall efficiency, resulting in a more environmentally friendly performance of these systems. For automotive fuel and coolant systems, hybrid nanofluids are gaining appeal due to their remarkable ability to enhance thermal performance and accelerate heat transfer rates. Ternary-hybrid nanofluids, which combines three different types of nanoparticles in a wide range of mixing ratios, are an intriguing but mostly speculative concept. Optimizing the mixing ratio for effective heat transfer characteristics is important for energy applications. A unique Al2O3/ZnO/Fe3O4 ternary nanofluid is synthesized and its density is measured in this investigation. The nanofluid preparation included three different mixing ratios (1:1:1, 2:1:1, and 1:2:1), with the volume fraction between 0.5 % and 1.25 %. This study also includes a discussion of the density prediction analysis. The result shows that at a temperature of 25 °C and a volume fraction of 1.25 %, the maximum density is determined to be 1165 kg/m3. The Random Forest algorithm gives the best prediction accuracy with an R2 value of 0.928.

Investigation of composition, antioxidant, antimicrobial and cytotoxic characteristics from Juniperus sabina and Ferula communis extracts.

Plants have been one the most valuable sources of biologically active compounds. This study investigates the chemical composition, as well as the antioxidant, antimicrobial, and cytotoxic activities of methanolic and ethanolic extracts from Juniperus sabina and Ferula communis leaves, grown in Cyprus. Total phenolic and flavonoids content of methanol and ethanol extracts were quantified. Chemical constituents of the leaf extracts were analysed using gas chromatography/mass spectrometry (GC/MS). Mome inositol was the predominant component in the J. Sabina's extracts. The most dominant component in F. communis ethanolic extract was phytol, while in FCL methanolic extract 1,3,4,5 tetrahydroxycyclohexanecarboxylic acid. Antioxidant activities were evaluated by 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free radical-scavenging ability. Antioxidant activity results revealed concentration dependent activity for methanolic and ethanolic extracts from the plant leaves. Antibacterial activity of plant extracts was tested against Gram-negative and Gram-positive bacteria using disk diffusion and minimal inhibitory concentration methods. Cytotoxic activity of plant extracts were evaluated on MCF-7 and MDA-MB-231 breast cancer cell lines, where they demonstrated their potential on the viability of both cell lines. The biological activity revealed by plants is due to the bioactive compounds found in the extracts. These bioactive components could be used as anticancer drug candidates.

Role of energy consumption and trade openness towards environmental sustainability in Turkey.

The growth of financial services has been critical in Turkey's pursuit of economic growth objectives throughout the last two decades. Nevertheless, it cannot be denied that it has a negative impact on environmental quality. Based on this, in the current paper, the effect of energy use, trade openness, and financial development on the load capacity factor (LCF) is explored for Turkey between 1965 and 2018. In doing so, a series of quantile approaches such as quantile cointegration (QC), quantile-on-quantile regression (QQR), nonparametric causality-in-quantiles (NCQ), and quantile regression (QR) are used. The results generated from the QQR and also validated by the QR reveal that in the majority of the quantiles, primary energy use, trade openness, and financial development impact the LCF negatively. These results suggest that primary energy use, trade openness, and financial development damage environmental quality. Furthermore, the findings gathered from the quantile causality disclose that all primary energy use, trade openness, and financial development can forecast LCF in the majority of the quantiles. Based on the research outcomes, policies, which may aid to solve the damaging environmental effects of the primary energy use, trade openness, and financial sector development in Turkey are recommended.

Freeze-dried crosslinked anionic hydrogels composed of poly(vinyl pyrrolidone) and poly(vinyl alcohol): synthesis, characterization and degradability performance.

PURPOSE: Poly(vinyl pyrrolidone) (PVP) and poly(vinyl alcohol) (PVA) has enticed significant research interest and are acknowledged among the principal volume of synthetic polymers that have been fabricated globally for nearly one century. This is as a result of their excellent attributes which dictated its wide-ranging usage in a range of applications, chiefly in medical field. The investigation is aimed at preparing PVP/PVA hydrogels using freeze drying technique for its characterization and accessing the biodegradability of the prepared hydrogel. METHODS: Scanning electron microscopy and Fourier transform infrared spectroscopy were employed for the description of the morphology and chemical composition of the prepared hydrogels. More characterization studies were implemented by measurement of apparent density, porosity, swelling ratio and crystallinity of the fabricated hydrogel with the use of X-ray diffractometer (XRD). The biodegradability of the prepared hydrogel was also carried out in vitro in phosphate buffered saline. RESULTS: As the PVP content increased the percentage of porosities from 45.00 ± 1.00% to 81.80 ± 0.20%, which was also accompanied by an increase in density. The prepared hydrogel showed increase in swelling ratio as the PVP content increased, the highest swelling ratio was found in PP4 with 95.58% with the least swelling time of 4 minutes. CONCLUSIONS: To sum it up, PVP plays a role as network and performance regulator in this sort of anisotropic hydrogels. This investigation offers a fascinating means of regulating morphology and general characteristics of the PVA-based anisotropic hydrogels.

Biogenic Synthesis and Characterization of Chitosan-CuO Nanocomposite and Evaluation of Antibacterial Activity against Gram-Positive and -Negative Bacteria.

Chitosan-copper oxide (CHT-CuO) nanocomposite was synthesized using olive leaf extract (OLE) as reducing agent and CuSO4⋅5H2O as precursor. CHT-CuO nanocomposite was prepared using an in situ method in which OLE was added to a solution of chitosan and CuSO4⋅5H2O mixture in the ratio of 1:5 (v/v) and heated at a temperature of 90 °C. The obtained CHT-CuO nanocomposite was characterized using field emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), ultraviolet-visible (UV-Vis) spectrophotometry, energy-dispersive X-ray spectroscopy (EDAX), Fourier transform infrared spectroscopy (FTIR), and high-resolution transmission electron microscopy (TEM). TEM results indicated that CHT-CuO nanocomposite are spherical in shape with size ranging from 3.5 to 6.0 nm. Antibacterial activity of the synthesized nanocomposites was evaluated against Gram-positive (Bacillus cereus, Staphyloccous haemolytica and Micrococcus Luteus) and Gram-negative (Escherichia coli, Pseudomonas citronellolis, Pseudomonas aeruginosa, kliebisella sp., Bradyrhizobium japonicum and Ralstonia pickettii) species by cup platting or disc diffusion method. Overall, against all tested bacterial strains, the diameters of the inhibition zone of the three nanocomposites fell between 6 and 24 mm, and the order of the antimicrobial activity was as follows: CuO-1.0 > CuO-0.5 > CuO-2.0. The reference antibiotic amoxicillin and ciprofloxacin showed greater activity based on the diameter of zones of inhibition (between 15−32 mm) except for S. heamolytica and P. citronellolis bacteria strains. The nanocomposites MIC/MBC were between 0.1 and 0.01% against all tested bacteria, except S. heamolityca (>0.1%). Based on MIC/MBC values, CuO-0.5 and CuO-1.0 were more active than CuO-2.0, in line with the observations from the disc diffusion experiment. The findings indicate that these nanocomposites are efficacious against bacteria; however, Gram-positive bacteria were less susceptible. The synthesized CHT-CuO nanocomposite shows promising antimicrobial activities and could be utilized as an antibacterial agent in packaging and medical applications.

Effect of extraction temperature and solvent type on the bioactive potential of Ocimum gratissimum L. extracts.

Ocimum gratissimum is a shrub that belongs to the Lamiaceae family of plants. Despite the known biological activities and ethnomedicinal applications, comparative evaluation of the effects of different extraction techniques on the chemical and bioactive properties of O. gratissimum extracts has not yet been performed. This study adopted different analytical techniques to determine the effect of extraction temperature and solvent type on the phytochemical and bioactive properties of O. gratissimum extracts. Chemical profiling showed increased concentrations of compounds for both the ethanolic and methanolic extracts compared to the water extracts. The results also revealed that the extraction temperature had an effect on the total phenolic content and radical-scavenging properties of the different extracts. The antioxidant kinetic modeling achieved the best fit when using the second-order kinetic model. Methanolic extracts had the highest levels of antibacterial activity against Escherichia coli, Bacillus cereus, Staphylococcus aureus, and Salmonella typhimurium. At high concentrations, all extracts lowered the viability of the breast cancer cell line MDA-MB-231. In conclusion, the chemical and bioactive properties of all extracts showed significant dependence on the extraction temperature and solvent type. With proper extraction methods, they boast a wide range of promising applications in the medical, pharmaceutical, and food industries.

Chitosan And N, N, N-Trimethyl Chitosan Nanoparticle Encapsulation Of Ocimum Gratissimum Essential Oil: Optimised Synthesis, In Vitro Release And Bioactivity.

BACKGROUND: The encapsulation of plant essential oils (EOs) with polymeric materials (e.g. chitosan (CS) and N, N, N-trimethyl chitosan (TMC)) and the further reduction of the polymers into their nano sizes are gaining research interest in nanotechnology due to potential applications in medical drug delivery systems as well as the food and pharmaceutical industry. The present study reports a novel approach for the synthesis of Ocimum gratissimum essential oil (OGEO)-loaded CS and TMC nanoparticles with distinct bioactive and physiochemical properties. METHODS: The OGEO-loaded CS and TMC nanoparticles were characterised using various microscopic and spectroscopic techniques. The bioactive compounds in Ocimum gratissimum methanolic extract (OG-MeOH) and EOs was evinced with gas chromatography-mass spectrometry (GC-MS). Total phenolic content (TPC) of OGEO and OG-MeOH was determined using the Folin-Ciocalteu method. The in vitro drug release kinetic pattern was ascertained by membrane dialysis, while antioxidant activity was determined by the 2,2-diphenyl-1picrylhydrozyl (DPPH) free radical scavenging method. The disc diffusion method was used for antibacterial activity evaluation, while MTT and a trypan blue dye exclusion assay were used to assess cytotoxic activity on MDA-MB-231 breast cancer cells. RESULTS: GC-MS analysis revealed components that have not been previously reported for Ocimum gratissimum. The maximum OGEO cumulative drug release percentage in vitro was observed at pH 3 for both OGEO-loaded chitosan nanoparticles (OGEO-CSNPs) and OGEO-loaded N, N, N-trimethyl chitosan nanoparticles (OGEO-TMCNPs). The antioxidant activity of OGEO-CSNPs and OGEO-TMCNPs never reached a steady state after 75 h. OGEO-TMCNPs exhibited antibacterial activity at a lower concentration for both Gram-negative and Gram-positive food pathogens. In vitro cytotoxicity revealed the increased toxicity of OGEO-TMCNPs on MDA-MB-231 breast cancer cell lines. CONCLUSION: OGEO-loaded CS and TMC nanoparticles were synthesised using a novel material optimisation approach. The synthesised nanoparticles have shown a promising application in the pharmaceutical and food industries.

Biosynthesis of zinc oxide nanoparticles using Albizia lebbeck stem bark, and evaluation of its antimicrobial, antioxidant, and cytotoxic activities on human breast cancer cell lines.

BACKGROUND: Biocompatibility and stability of zinc oxide nanoparticles (ZnO NPs) synthesized using plants is an interesting research area of study in nanotechnology, due to its wide applications in biomedical, industrial, cell imaging, and biosensor fields. The present study reports the novel green synthesis of stable ZnO NPs using various concentrations of zinc nitrate (0.01M, 0.05M, 0.1M) and Albizia lebbeck stem bark extracts as an efficient chelating agent. Antimicrobial, antioxidant, cytotoxic, and antiproliferative activities of the synthesized NPs on human breast cancer cell lines were evaluated using different assays. METHODS: Characterization of the synthesized ZnO NPs were carried out using various spectroscopic and microscopic techniques. Antimicrobial activity evaluation using disc diffusion method, antioxidant activity using hydrogen peroxide (H2O2) free radical scavenging assay and cytotoxic activity on MDA-MB 231 and MCF-7 using tryphan blue dye exclusion and MTT assay. RESULTS: The UV-vis spectroscopy result revealed an absorption peak in the range of 370 nm. The involvements of A. lebbeck bioactive compounds in the stabilization of the ZnO NPs were confirmed by X-ray diffraction and Fourier transform infrared analysis. Zeta sizer studies showed an average size of 66.25 nm with a polydisparity index of 0.262. Scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) analyses results revealed irregular spherical morphology and the presence of primarily Zn, C, O, Na, P, and K, respectively. The biosynthesized ZnO NPs revealed strong antimicrobial potentials against various gram-negative and gram-positive bacterial pathogens. Antioxidant activities carried out using H2O2 free radical scavenging assay revealed higher IC50 values of 48.5, 48.7, and 60.2 µg/mL for 0.1M, 0.05M, and 0.01M ZnO NPs, respectively. Moreover, the biosynthesized ZnO NPs showed significant cytotoxic effects on MDA-MB 231 and MCF-7 breast cancer cell lines (P< 0.001, n≥3) in a concentration-dependent manner. CONCLUSION: Overall, various concentrations of ZnO NPs were synthesized through a stable, simple, and eco-friendly green route via the use of A. lebbeck stem bark extract. The biosynthesized ZnO NPs showed strong antimicrobial, antioxidant and cytotoxic activity against strongly and weakly metastatic breast cancer cell lines.

Physiochemical characterization, antioxidative, anticancer cells proliferation and food pathogens antibacterial activity of chitosan nanoparticles loaded with Cyperus articulatus rhizome essential oils.

Essential oil of Cyperus articulatus have known bioactivities, the qualitative chemical composition analysis of the Essential Oils (EOs) by Gas Chromatography-Mass Spectrometry (GC-MS) revealed the presence of new compounds not previously known to the plant rhizome which includes, sesquiterpenes, monoterpenes, nootkatone, 6-methyl-3,5-heptadien-2-one, retinene, nopinone, cycloeucalenol, anozol, toosendanin, furanone, ethanone and vitamin A. Cyperus articulatus Essential Oils (CPEOs) loaded Chitosan Nanoparticles (CSNPs) was successful synthesized using an oil-in-water mixture and ionic gelation method and were characterized by Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR) and UV-Vis spectrophotometry. CPEOs had more radical-scavenging bioactivity in vitro than CSNPs and CPEO-CSNPs at initial storage times. CPEO-CSNPs showed the highest (P < 0.05) antioxidant activity over a prolonged period of time. Antimicrobial activity of two strains of bacteria, Staphylococcus aureus (ATCC6538), and Escherichia coli (ATCC 8739) showed that all CPEO-loaded chitosan nanoparticle inhibited bacterial growth at lower (P < 0.05) CPEO-CSNP concentration (5 mg/mL MIC) compared to free CPEOs (10 mg/mL MIC). Trypan blue in vitro exclusion assay showed CPEO-CSNPs to be more cytotoxic against MDA-MB-231 breast cancer cells after 48 h. The bioactivity and physiochemical properties of CPEO-CSNPs have shown promising applications in food and pharmaceutical industries.

Effective and reusable nano-silica synthesized from barley and wheat grass for the removal of nickel from agricultural wastewater.

In the present study, a comparative analysis was performed on the extraction of nickel ions (Ni2+) from agricultural wastewater using nanosilica (NS) synthesized from barley (NS-B) and wheat (NS-W) grass waste with a yield of 92.4%. The experimental procedure was conducted on barley and wheat waste to obtain an 85% pure NS that served as the adsorbent for nickel extraction in wastewater. The NS was characterized and studied using X-ray fluorescence (XRF), which demonstrated that NS synthesized from barley contained 94.2% SiO2, while NS synthesized from wheat contained 93.0% SiO2. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) were used to determine the surface morphology of the nanoparticles. The energy-dispersive X-ray (EDX) analysis and Fourier transform infrared (FTIR) analysis were used to determine the elements and functional groups of the synthesized particles, respectively. Lastly, particle size and surface area analyses were performed using the Brunauer-Emmett-Teller (BET) method, which determined that the nanoparticles were 70 and 102 nm for NS-B and NS-W, respectively. The adsorption of nickel ions from agricultural wastewater was studied at various concentrations (10-200 mg/L). The kinetic models indicate that sorption equilibrium time was 65 min and that the reaction followed the pseudo-first-order kinetics model with a regression coefficient (R2) of 0.9289. Corresponding studies indicated that the Freundlich isotherms best describe the sorption reaction with an R2 value of 0.9958, which indicates the multilayer adsorption of nickel on the adsorbent. In their standard and real states, the samples indicated that NS-B and NS-W provided high levels of nickel (Ni2+) removal at 95 and 90%, respectively.

Synthesis, characterization, antimicrobial and antimetastatic activity of silver nanoparticles synthesized from Ficus ingens leaf.

Cancer incidence is still increasing due to inadequate responsive treatments. Inertness and biocompatibility of nanoparticles synthesized using plant extracts have shown therapeutic applications and make it to be a good anti-cancer candidates. This study is a recent novel spotlight that synthesized silver nanoparticle from Ficus ingens leaf extract (FILE) and studied its anti-metastatic and anti-bacterial activity. The chemical and surface analysis of the synthesized FILE silver nanoparticles (FILE-AgNPs) was studied using UV-visible, Fourier transform infrared (FTIR), X-ray diffraction (XRD), zeta sizer, atomic force microscopy (AFM) and scanning electron microscopy (SEM). Gas chromatography mass spectrometric (GC-MS) and quantitative photochemical analyses were also carried out. The antimicrobial activity of FILE-AgNPs was found to be effective with MIC of 10 µg/mL for E. coli and 20 µg/mL for S. typhi and B. cereus with significance difference. Toxicity, proliferation and anti-metastatic potential of FILE-AgNPs were studied on MDA-MB 231 cell models using tryphan blue, MTT and wound heal assay, respectively. FILE-AgNPs showed the ability to inhibit metastasis of MDA-MB 231 cells in dose-dependent manner in which 10 µg/mL and 5 µg/mL inhibit by 96% and 75%, respectively. The synthesized FILE-AgNPs are remarkable candidates for treatment of cancer cases and other cancer related cases.

Comparison of protein- and polysaccharide-based nanoparticles for cancer therapy: synthesis, characterization, drug release, and interaction with a breast cancer cell line.

In this study, human serum albumin (HSA) was used as a protein-based material and poly (3-hydroxybutyrate) (PHB)-carboxymethyl chitosan (CMCh) as a polysaccharide-based material for the production of nanoparticles to be used as nanocarriers in cancer therapy. HSA and PHB-CMCh nanoparticles were prepared and characterized with a Zeta Sizer, Fourier transform infrared spectroscopy, scanning electron microscopy, and atomic force microscope. The effects of the pH value of the suspending medium and the amounts of crosslinker and polymer concentration on nanoparticle size and size distribution were investigated. The anticancer-agent etoposide was used as a model drug and encapsulated in nanoparticles to obtain drug release profiles. The entrapment efficiency of HSA nanoparticles was found to be greater than that of PHB-CMCh nanoparticles. To achieve "active" targeting of cancer cells, the nanoparticles were modified with concanavalin A. In the final step of the study, the interaction of nanoparticles with cancer cells was investigated in cytotoxicity and cellular uptake studies.

Emerging technologies for assembly of microscale hydrogels.

Assembly of cell encapsulating building blocks (i.e., microscale hydrogels) has significant applications in areas including regenerative medicine, tissue engineering, and cell-based in vitro assays for pharmaceutical research and drug discovery. Inspired by the repeating functional units observed in native tissues and biological systems (e.g., the lobule in liver, the nephron in kidney), assembly technologies aim to generate complex tissue structures by organizing microscale building blocks. Novel assembly technologies enable fabrication of engineered tissue constructs with controlled properties including tunable microarchitectural and predefined compositional features. Recent advances in micro- and nano-scale technologies have enabled engineering of microgel based three dimensional (3D) constructs. There is a need for high-throughput and scalable methods to assemble microscale units with a complex 3D micro-architecture. Emerging assembly methods include novel technologies based on microfluidics, acoustic and magnetic fields, nanotextured surfaces, and surface tension. In this review, we survey emerging microscale hydrogel assembly methods offering rapid, scalable microgel assembly in 3D, and provide future perspectives and discuss potential applications.

Release of magnetic nanoparticles from cell-encapsulating biodegradable nanobiomaterials.

The future of tissue engineering requires development of intelligent biomaterials using nanoparticles. Magnetic nanoparticles (MNPs) have several applications in biology and medicine; one example is Food and Drug Administration (FDA)-approved contrast agents in magnetic resonance imaging. Recently, MNPs have been encapsulated within cell-encapsulating hydrogels to create novel nanobiomaterials (i.e., M-gels), which can be manipulated and assembled in magnetic fields. The M-gels can be used as building blocks for bottom-up tissue engineering to create 3D tissue constructs. For tissue engineering applications of M-gels, it is essential to study the release of encapsulated MNPs from the hydrogel polymer network and the effect of MNPs on hydrogel properties, including mechanical characteristics, porosity, swelling behavior, and cellular response (e.g., viability, growth). Therefore, we evaluated the release of MNPs from photocrosslinkable gelatin methacrylate hydrogels as the polymer network undergoes biodegradation using inductively coupled plasma atomic emission spectroscopy. MNP release correlated linearly with hydrogel biodegradation rate with correlation factors (Pearson product moment correlation coefficient) of 0.96 ± 0.03 and 0.99 ± 0.01 for MNP concentrations of 1% and 5%, respectively. We also evaluated the effect of MNPs on hydrogel mechanical properties, porosity, and swelling behavior, as well as cell viability and growth in MNP-encapsulating hydrogels. Fibroblasts encapsulated with MNPs in hydrogels remained viable (>80% at t = 144 h) and formed microtissue constructs in culture (t = 144 h). These results indicated that MNP-encapsulating hydrogels show promise as intelligent nanobiomaterials, with great potential to impact broad areas of bioengineering, including tissue engineering, regenerative medicine, and pharmaceutical applications.

Preparation and characterization of magnetically responsive bacterial polyester based nanospheres for cancer therapy.

Polyhydroxyalkanoates (PHA) are natural, thermoplastic polyesters and due to their biocompatible and biodegradable properties they are good alternatives for the production of scaffolds for engineered tissues or nanoparticles for drug delivery. As a member of polyhydroxyalkanoate family, polyhydroxybutyrates (PHB) have been widely used as a biomaterial for in vitro and in vivo studies since their mechanical properties are very similar to conventional plastics. By using multi-emulsion technique, iron oxide particles were coated with polyhydroxybutyrate (PHB) polymer synthesized from Alcaligenes eutrophus bacteria and the magnetic carrier system was prepared accordingly. The bare nanoparticles and magnetic nanoparticles were morphologically, structurally and magnetically characterized by using Scanning electron microscope (SEM) and Atomic force microscope (AFM); Fourier Transform Infrared Spectrometry (FTIR), and Electron Spin Resonance (ESR) and Vibrating Sample Magnetometer (VSM) techniques, respectively. Particle size of PHB nanoparticles was determined by Zeta Sizer. It was found that the smallest particles were in the range of 239.43 +/- 5.25 nm in diameter. Concanavalin-A (Con-A) was used for targeting the cancer cells while etoposide was used as drug. Con-A and etoposide were loaded onto the particles. Release studies of etoposide were evaluated and the system was optimized for the further in vivo applications. Finally different formulation magnetic PHB nanoparticles cytotoxicity were evaluated in cell culture studies and used HeLa cell line (cervical cancer cells) as a cancer cells and L929 cells (mouse fibroblast cells) as a non-cancer cell line.