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In this project, different photosensitizers were prepared using different ratios of nickel, manganese, and iron. Then, multiple analysis were performed to evaluate their efficiency, and the most suitable one was used to be coated by hyaluronic acid to improve the nano-platform's biocompatibility and target ability. Moreover, another chemical targeting agent (riboflavin) was used to further improve the target ability of the prepared nano-platform. Different spectroscopies and thermal analysis were used to determine the physical and chemical characteristics of the prepared nano-platform. Also, in order to determine the biocompatibility of the nano-platform, in vitro and in vivo tests such as blood hemolysis, blood aggregation and lethal dose were performed. Then, an anti-cancer agent (curcumin) was loaded on the selected nano-platform to makes us able utilizing the synergistic effect of chemotherapy and photodynamic therapy simultaneously. Finally, the cell cytotoxicity results showed that the prepared nano-platform had a great anti-cancer potential which can make it a great candidate as a dual photo and chemo therapy agent for treatment of breast cancers.

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This review provides a summary of recent progress in the development of different nano-platforms for the efficient synergistic effect between photodynamic therapy and chemotherapy. In particular, this review focuses on various methods in which photosensitizers and chemotherapeutic agents are co-delivered to the targeted tumor site. In many cases, the photosensitizers act as drug carriers, but this review, also covers different types of appropriate nanocarriers that aid in the delivery of photosensitizers to the tumor site. These nanocarriers include transition metal, silica and graphene-based materials, liposomes, dendrimers, polymers, metal-organic frameworks, nano emulsions, and biologically derived nanocarriers. Many studies have demonstrated various benefits from using these nanocarriers including enhanced water solubility, stability, longer circulation times, and higher accumulation of therapeutic agents/photosensitizers at tumor sites. This review also describes novel approaches from different research groups that utilize various targeting strategies to increase treatment efficacy through simultaneous photodynamic therapy and chemotherapy.

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The medicinal plant, Scutellaria orientalis, is used for the treatment of several diseases in North-western of Iran. The purpose of this study was to investigate the phytochemical content, cytotoxicity assay against SW-480 and HCT-116 cells and anti-haemolytic activities using HPLC-PDA, GC/MS, MTT and spectrophotometry methods, respectively. Phytochemical screening revealed the presence of different terpenoids and flavonoids such as baicalin, tricin and wogonin and also some of the other medicinally active compounds such as conhydrine and cannabidiol. MTT results revealed that HCT-116 cells were more sensitive to examined extracts compared with SW-480 cells. Methanol extract had the most anti-proliferative activity against HCT-116 and SW-480 cells at 48 h with IC50 values of 614.5 and 592.3 µg/mL, respectively. Also, all samples had no significant haemolytic effect on human erythrocytes. Our results revealed that S. orientalis root extract has a promising anticancer activity, indicating the presence of major anti-cancer agents on human colon cell lines.

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In this project, a biocompatible block copolymer including poly ethylene glycol and poly caprolactone was synthesized using ring-opening reaction. Then, the copolymer was conjugated to folic acid using lysine as a linker. Also, curcumin (CUR) was used as a therapeutic anticancer agent. Nanoprecipitation method was used to prepare CUR-loaded polymeric micelles. Different methods including Fourier-transform infrared spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering (DLS) were used to characterize the prepared nanocarriers (NCs). MTT assay and hemolysis assay were used to evaluate in vitro anticancer efficiency and biocompatibility of the prepared NCs, respectively. The results proved efficiency of NCs as a drug delivery system (DDS) in various aspects such as physicochemical properties and biocompatibility. Also, in vivo results showed that NCs did not show any severe weight loss and side effects on mice, and the anti-cancer study results of the CUR-loaded NCs proved that the conjugation of folic acid on the surface of NCs as a targeting agent could increase the therapeutic efficacy of CUR.

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In the present study, we successfully synthesized nanocarriers (NCs) based on Y-shaped miktoarm copolymers, Poly Ethylene Glycol-Lysine-(Poly Caprolactone)2 (PEG-Lys-PCL2), which were loaded by baicalein (B) through the nanoprecipitation process to assess their in-vitro and in-vivo properties. We applied various methods and measurements including proton nuclear magnetic resonance (HNMR), dynamic light scattering (DLS), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), MTT assay, hemolysis test, lethal dose, real-time PCR, and Morris water maze. The results of DLS indicated that the size and zeta potential of the obtained NCs and B-loaded NCs were acceptable. Also, in-vivo and in-vitro biocompatibility examinations proved that miktoarm-based NCs were safe, and all rats treated with miktoarm-based NCs did not exhibit any remarkable weight loss during the experiment. The results of the Morris water maze (in-vivo test) revealed that the normal saline-treated group, as well as B-miktoarm + Scopolamine (M + B + S) and B-miktoarm-Tween80 + Scopolamine (M + B + T + S) pretreatment groups, spent more time in the target quadrant. Thus, this experiment showed that pretreatment of rats with M + B + S and M + B + T + S had the most effects on spatial memory. According to quantitative PCR analysis, we hypothesized that, in comparison with other experimental groups, pretreatment of rats with M + B + T + S could be more effective in preventing cholinergic dysfunction, brain oxidative stress and cognitive deficits which cause by Scopolamine HBr. This outcome may be partially due to the upregulation of DHCR24, SELADIN, and SIRT6 in entire of the hippocampal region of normal saline-treated and M + B + T + S pretreatment groups. These results may be because mimicking the cell membrane structure would be an excellent feature for miktoarm, and partial coating of Tween-80 can play a critical role for PEG-Lys-PCL2-based NCs in crossing the brain cell membrane, and they can easily be uptaken by the cells. Eventually, all of the obtained data confirmed that PEG-Lys-PCL2 miktoarm star copolymers are suitable for delivering therapeutic agents to the brain for the treatment of Alzheimer's disease (AD). Also, it seems that baicalein should be taken into account as a potent compound for the treatment of AD.

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In The present project, a variety of MnFe2O4 (Mn) and Cr2Fe6O12 (Cr)-based nanocarriers (NCs) were synthesized as photosensitizer and NCs for delivery of chemotherapeutic curcumin (CUR) and provide a new structure for Photodynamic Therapy (PDT). For determining efficiency of NCs release study, MTT assay, lethal dose test and hemolysis assay were carried out. The release study showed the release of CUR from NCs was pH-dependent, but, every NCs had its own behavior for releasing the drug. The data acquired from the release study showed the CUR release from Mn can reach to over 90% at acidic media instead of 41% at neutral media. However, the CUR released from Cr were approximately equal as Cr had equal zeta potential at both media. Hemolysis activity and lethal dose test displayed the cytotoxicity of NCs was neglectable at both in vitro and in vivo study. Also, the results of anti-cancer activity assay (MTT assay) showed that both of Cr and Mn NCs are suitable systems for PDT. Therefore, the results demonstrated that Mn is suitable NCs for PDT and anticancer drugs delivery of therapeutic drugs.

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PURPOSE: In this study, methoxy poly (ethylene glycol)-poly (ε-caprolactone) (mPEG-PCL) di-block copolymers were synthesized. The purpose of this work is to investigate the in vivo anti-inflammatory effects of simvastatin-loaded micelles. METHODS: The structure of synthesized copolymers was characterized by using HNMR, FTIR, and GPC techniques. Simvastatin was encapsulated in micelles through a single-step nano-precipitation method, leading to the formation of simvastatin-loaded mPEG-PCL (simvastatin-mPEG-PCL) micelles. In this study, the anti-inflammatory effects of simvastatin/mPEG-PCL micelles versus indomethacin were investigated in acute inflammation-induced rats. The paw edema thickness was measured 1, 2, 3, and 4 h after injection of formulation. The inhibition of edema in various groups were calculated and reported by percentages. RESULTS: The results showed that the zeta potential of micelles was about -14.9 ± 0.47 mV and the average size was in range of 66.10 ± 0.34 nm. Simvastatin was encapsulated in mPEG-PCL micelles with a loading capacity of 9.63 ± 0.87% and an encapsulation efficiency of 64.20 ± 0.79%. Simvastatin and simvastatin-mPEG-PCL micelles showed significant anti-inflammatory activity in the present study. CONCLUSIONS: This study revealed that simvastatin and simvastatin/mPEG-PCL micelles both have anti-inflammatory effects and suggested that statins have potential anti-inflammatory activity along with their lipid lowering properties.

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In this project, a core-shell polymersome based on miktoarm star-copolymer:methoxy poly-ethylene glycol-lysine-(poly-caprolactone)2 was synthesized by a new method as controlled targeted drug delivery systems for codelivery of the chemotherapeutic methotrexate (MTX) and curcumin (CUR). Some properties of these nanocarriers (NCs), such as surface morphology, structure, surface charge, stability, and biocompatibility, were evaluated by proton nuclear magnetic resonance, dynamic scanning colorimetry, Fourier-transform infrared spectroscopy, dynamic light scattering, atomic force microscopy, critical aggregation concentration, hemolysis test, MTT assay, and lethal dose 50 (LD50). The AFM results showed that the uniform spherical morphology of NCs have an average size of about ∼60 nm. The drug loading of NCs was about 14.13 and 10.93% for CUR and MTX, respectively. The NCs revealed pH-sensitivity in drug release. The release of drugs from miktoarm-based NCs in neutral pH was lower than in acidic medium because of faster degradation of polymersome in acidic environment. MTT assay results showed that the drug-loaded NCs did not show significant toxicity due to which cell viability maintain over 82% at 300 µg/mL concentration. Also, synthesized miktoarm showed hemolysis lower than 3%. This result was repeated in LD50, and all mice which treat with 5000 mg/kg were still alive after 24 h. These result confirmed safety of miktoarm star copolymer. Eventually, the goal of this study is the application of water-soluble star copolymers miktoarm with pH dependent release properties for designing a new drug delivery carrier and using CUR for enhancing anticancer properties of MTX. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2817-2826, 2018.

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