Application of nanoparticles in breast cancer treatment: a systematic review.

It is estimated that cancer is the second leading cause of death worldwide. The primary or secondary cause of cancer-related mortality for women is breast cancer. The main treatment method for different types of cancer is chemotherapy with drugs. Because of less water solubility of chemotherapy drugs or their inability to pass through membranes, their body absorbs them inadequately, which lowers the treatment's effectiveness. Drug specificity and pharmacokinetics can be changed by nanotechnology using nanoparticles. Instead, targeted drug delivery allows medications to be delivered to the targeted sites. In this review, we focused on nanoparticles as carriers in targeted drug delivery, their characteristics, structure, and the previous studies related to breast cancer. It was shown that nanoparticles could reduce the negative effects of chemotherapy drugs while increasing their effectiveness. Lipid-based nanocarriers demonstrated notable results in this instance, and some products that are undergoing various stages of clinical trials are among the examples. Nanoparticles based on metal or polymers demonstrated a comparable level of efficacy. With the number of cancer cases rising globally, many researchers are now looking into novel treatment approaches, particularly the use of nanotechnology and nanoparticles in the treatment of cancer. In order to help clinicians, this article aimed to gather more information about various areas of nanoparticle application in breast cancer therapy, such as modifying their synthesis and physicochemical characterization. It also sought to gain a deeper understanding of the mechanisms underlying the interactions between nanoparticles and biologically normal or infected tissues.

Effect of Trans-Anethole on Gene Expression of Steroidogenic Enzymes in the Ovary of Polycystic Ovary Syndrome Model Rate:.

BACKGROUND: The process of steroidogenesis is crucial to the normal function of the ovaries. In individuals with polycystic ovary syndrome (PCOS), the activity of related enzymes in this process is disrupted. In the present study, the effect of trans-anethole was investigated on gene expression of steroidogenesis enzymes in PCOS model rats. MATERIALS AND METHODS: In this experimental study, thirty female rats were divided into six groups (n=5 per group). Fifteen PCOS rats in three groups received intraperitoneal injections of distilled water, 50, and 80 mg/kg of trans-anethole, respectively. Also, 15 intact rats in three groups received intraperitoneal injections of distilled water, 50, and 80 mg/kg trans-anethole. The expression of steroidogenesis genes was determined using real-time reverse transcription polymerase chain reaction. RESULTS: The mRNA level of Cyp19 significantly increased in intact rats receiving 80 mg/kg trans-anethole compared to the control group. The Cyp19 level in PCOS groups was significantly reduced compared to the control group. The mRNA level of Cyp19 in PCOS groups that resived 50 or 80 mg/kg trans-anethole increased compared to PCOS rats, but this increase was not statistically significant. The mRNA level of Cyp17 did not significantly change in intact and PCOS rats that received trans-anethole compared to the control group. CONCLUSION: Trans-anethole may improve PCOS complications due to its involvement in regulating steroidogenesis.

Anti-Cancer and Anti-Bacterial Effects of Terfezia boudieri-Derived Silver Nanoparticles.

BACKGROUND: The use of nanoparticles has markedly increased in biomedical sciences. The silver nanoparticles (AgNPs) have been investigated for their applicability to deliver chemotherapeutic/antibacterial agents to treat cancer or infections disease. However, the existing chemical and physical methods of synthesizing AgNPs are considered inefficient, expensive and toxic. METHODS: Natural products have emerged as viable candidates for nanoparticle production, including the use of Terfezia boudieri (T. boudieri), a member of the edible truffle family. Accordingly, our goal was to synthesize AgNPs using an aqueous extract of T. boudieri (green synthesized AgNPs). Since certain infectious agents are linked to cancer, we investigated their potential as anti-cancer and antibacterial agents. RESULTS: The synthesis of AgNPs was confirmed by the presence of an absorption peak at 450nm by spectroscopy. The physico-chemical properties of green synthesized AgNPs were analyzed by UV-Vis, FT-IR, XRD, SEM, and TEM. In addition, their potential to inhibit cancer cell (proliferation and the growth of infectious bacteria were investigated. CONCLUSION: The size of nanoparticles ranged between 20-30nm. They exerted significant cytotoxicity and bactericidal effects in a concentration and time-dependent manner compared to T. boudieri extract alone. Interestingly, the synthesis of smaller AgNPs was correlated with longer synthesis time and enhanced cytotoxic and bactericidal properties.

Novel multi-targeted nanoparticles for targeted co-delivery of nucleic acid and chemotherapeutic agents to breast cancer tissues.

Selective delivery of drugs to damaged tissues favorable to reduce the side effects while enhancing the therapeutic efficacy. The purpose of the present study was the design and synthesis of multi-targeted nanoparticles for co-delivery of both drug and nucleic acid to cancer cells. In this study biocompatible compounds such as chitosan, polyethylene glycol (PEG), polycaprolactone (PCL), folic acid (FA) and glucose (Glu) were used to synthesize the FA-PEG-Chitosan-PCL-Chitosan-PEG-FA (FPCP) and Glu-PEG-Chitosan-PCL-Chitosan-PEG-Glu (GPCP) copolymers. Then, paclitaxel (PTX), oleic acid-coated FeCO nanoparticles (FeCO-OA) and 6-carboxy-fluorescein phosphoramidate (FAM)-labeled siRNA (siRNA-FAM) were encapsulated into either FPCP or GPCP, or both FPCP and GPCP (GFPCP), using the solvent evaporation technique. In vitro and in vivo biocompatibility and drug delivery efficiency of FPCP/FeCO-OA/PTX, GPCP/FeCO-OA/PTX and GFPCP/FeCO-OA/PTX nanoparticles were determined by recording the MTT assay, weight loss and tumor volume respectively. In addition, the ability of FPCP/FeCO-OA/siRNA-FAM, GPCP/FeCO-OA/siRNA-FAM, and GFPCP/FeCO-OA/siRNA-FAM gene transfer was determined using flow cytometry analysis. Moreover, the effects of applying an external magnetic field to the tumor site on the efficiency of drug delivery using FPCP/FeCO-OA/siRNA-FAM/PTX (NPsA), GPCP/FeCO-OA/siRNA-FAM/PTX (NPsB) and GFPCP/FeCO-OA/siRNA-FAM/PTX (NPsAB) were also investigated in the present study. No significant toxicity was observed for the FPCP and GPCP copolymers. Meanwhile, PTX encapsulated FPCP, GPCP and GFPCP exhibited greater anticancer activities against MCF-7 cells. The in vivo and in vitro results showed that the nanoparticles targeted with both folic acid and glucose increased drug and RNA transfer efficiency compared to when folic acid or glucose alone used. Also, the efficiency of PTX and siRNA-FAM delivery to tumor tissues by nanoparticles increased significantly by applying an external magnetic field to the tumor area. The hydrophobic interactions between different amphipathic copolymers in appropriate is an efficient and easy technique to synthesize complex and multifunctional nanoparticles.

Production of Erythropoietin-Specific Polyclonal Antibodies.

BACKGROUND: Erythropoietin, as a principal hormone promotes red blood cell production in bone marrow. Varieties of erythropoietin biosimilar are being produced by recombinant DNA technology in cell cultures. The detection or quantifi cation of these molecules are being performed by diff erent methods which some of theme such as Western blot and enzymelinked immunosorbent assay (ELISA) require specifi c antibodies. High cost, inappropriate shipping (cold chain failures), reduced sensitivity and thus poor detection performance are common pitfalls of using commercial kits for performing immunological tests. OBJECTIVES: To produce in-house polyclonal antibody against active pharmaceutical ingredient (API) of recombinant human erythropoietin (rh-EPO) was the aim of this study. MATERIALS AND METHODS: Two healthy female albino rabbits were injected four times in 14 days interval using rh-EPO API as antigen. The produced antibody was separated from plasma via either caprylic acid or saturated ammonium sulfate precipitation and the results were compared from each purification methodologies. The antibody was further purified by ion exchange chromatography. Acceptable purity and good immunogenicity were detected respectively by SDS-PAGE and western blot analysis. The purified antibody was compared with a commercial kit to determine rh-EPO concentration in diff erent steps of production batches via ELISA. RESULTS: The purity of antibodies after ion exchange chromatography, obtained from caprylic acid and ammonium sulfate precipitation were 97 and 80%, respectively. CONCLUSIONS: As producing in house kits is one of the important challenges of bio- pharmaceutical manufacturers, a simple, cost- and time-effective, and easy to scale up strategy for making in-house polyclonal antibody was set up. Caprylic acid precipitation resulted higher purity than ammonium sulfate and fi nally purified antibody (97% purity) used as a capture antibody in sandwich ELISA test was able to detect erythropoietin antigen as sensitive (100%) and specifi c (100%) as commercial kits.

A Study of Acute Poisoning Cases Admitted to the University Hospital Emergency Department in Tabriz, Iran.

Chemical substances have an important threat due to extensive use in medicine, agriculture, industry and environment. In this retrospective study, etiological and demographic characteristics of acute poisoning cases admitted to a hospital in Iran were investigated. We compared these data with those reported from other parts of the country and the international experiences to evaluate any difference if exists. 7 052 poisoned cases admitted to the hospital from April 2006 to March 2013, by data collected from the medical record in poison center section. According to our results there is a predominance of male patients and the majority of the poisoned patients were between 20-30 years old. Drug poisoning was the most common cause of poisonings. The most frequently involved drugs were benzodiazepines and antidepressants. The seasonal distribution of our study showed a peak in summer. To prevent acute poisonings, the social education about the risk assessment of central nervous system-acting drugs and reduction of the exposure period of people to pesticides are recommended. This study suggested a proper educational program for the public and primary care units. Our results provide useful information for preventive strategies.

Structural studies of hen egg-white lysozyme dimer: comparison with monomer.

A facile method for the formation of covalent bonds between protein molecules is zero length cross-linking. This method enables the formation of cross-links without use of any chemical reagents. Here, we report a cross-linking method for lysozyme and some structural studies as well as catalytic activity assay was performed on lysozyme dimer. The results showed that catalytic activity of lysozyme dimer was the same as monomer. Also, the GdnCl-induced equilibrium unfolding of hen egg-white lysozyme monomer and dimer at pH 2 was studied over a temperature range of 290.7-303.2 K by means of CD spectroscopy. The lack of coincidence between two unfolding curves at 222 and 289 nm in lysozyme dimer was observed, which suggested the existence of intermediate state in unfolding process, while lysozyme monomer showed a single cooperative transition. Thus, the thermodynamic parameters were estimated on the basis of two-state mechanism for lysozyme monomer and three-state one for lysozyme dimer. These results indicated that zero length cross-linking can stabilize the intermediate, so the population of intermediate increased. Our results offer a special opportunity to study the role of intermediates in protein folding mechanisms. In addition thermal unfolding of monomer and dimer in 222 nm was achieved.

Application of zero-length cross-linking to form lysozyme, horseradish peroxidase and lysozyme-peroxidase dimers: Activity and stability.

A facile method for the formation of covalent bonds between protein molecules is zero-length cross-linking. This method enables the formation of cross-links without use of any chemical reagents. Here, the cross-linking is performed for lysozyme, peroxidase (a glycoprotein) and between lysozyme-peroxidase by the method of Simons et al. [B.L. Simons, M.C. King, T. Cyr, M.A. Hefford, H. Kaplan, Covalent cross-linking of protein without chemical reagents, Protein Sci. 2002, 11, 1558-1564]. Approximately one-third of the total lysozyme becomes cross-linked and the dimer form was the major product for both enzymes. This modification induced some changes in the kinetic properties of the dimer peroxidase, as evident by two-fold increasing of V(max) compared to the monomer but the enzymatic activity of cross-linked lysozyme dimer was the same as monomer. The activity of lysozyme dimer remained constant up to 10min at 80 degrees C, while peroxidase activity of both monomer and dimer began to decrease after heating. The structural changes of the enzymes were investigated by circular dichroism and intrinsic fluorescence techniques. Near UV result showed lysozyme possess a compact structure in the dimer form but disruption of tertiary structure of peroxidase dimer was observed. Also conformational changes were detected and discussed by intrinsic fluorescence experiments. Effect of several metals in the formation of lysozyme dimer showed that Co(2+) is the most effective one but its effect was marginal. At the end formation of heterogeneous dimer, peroxidase-lysozyme, was achieved using this method.