Hyaluronic acid coated spinel ferrite for combination of chemo and photodynamic therapy: Green synthesis, characterization, and in vitro and in vivo biocompatibility study.

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.

Hospital wastewater treatment using eco-friendly eugenol nanostructured lipid carriers: Formulation, optimization, and in vitro study for antibacterial and antioxidant properties.

In this study, nano-formulation has been used to tackle one of the most important environmental problems which can be considered a major threat to human health. We prepared some eco-friendly nanostructured lipid carriers (NLCs) as delivery agents to properly deliver an antibacterial agent (eugenol) into hospital wastewater in order to control bacterial growth. Eugenol-loaded nanostructured lipid carriers were prepared by hot high-speed homogenization. Then, the prepared nanocarriers were characterized using different techniques such as transmission electron microscopy, Fourier transform infrared, and dynamic scanning calorimetry. The turbidity assay and colony counting method were used to determine the ability of the prepared eugenol-loaded nanostructured lipid carriers to inhibit bacterial growth rate in the culture media and hospital wastewater, respectively. The mean size and zeta potential of NLC-eugenol were 78.12 ± 6.1 nm and -29.43 ± 2.21 mV, respectively. The results showed that the highest inhibitory effect of NLC-eugenol in culture media was seen in standard and wild Staphylococcus aureus strains (43.42% and 26.41%, respectively) with a concentration of 0.125 µM. The antibacterial activity of NLC-eugenol in sterile wastewater on wild strains of bacteria showed that the most effective concentration to reduce bacterial amounts was 0.125 µM on wild S. aureus and Enterococcus faecalis strains (38% and 33.47%, respectively) at 37°C. The NLC-eugenol with a concentration of 0.125 µM showed the greatest effect of reducing total microbial agents by 28.66% in hospital wastewater at 25°C. The highest antibacterial effect achieved using the 0.125 µM concentration is due to the egel phenomenon. Also, the mechanism of action of NLC-eugenol is cell wall destruction and eventually cell death. The results showed that NLC-eugenol with a concentration of 0.125 µM can reduce wild bacterial strains in sterilized wastewater and hospital wastewater, which can prove the great potential of the prepared eugenol-loaded nanostructured lipid carriers to control bacterial growth. PRACTITIONER POINTS: NLC is one of the safest biodegradable and environmentally friendly carriers, which is nontoxic for humans and the environment. Eugenol is a natural compound, which makes it less toxic for the environment while being toxic for bacteria. Therefore, our method has the least side effect in comparison with existing methods for wastewater treatment. The gradual release of eugenol from NLC nanoparticles can effectively control the pathogenic factors of wastewater.

Synergic Antitumor Effect of Photodynamic Therapy and Chemotherapy Mediated by Nano Drug Delivery Systems.

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.

Targeted drug delivery via folate decorated nanocarriers based on linear polymer for treatment of breast cancer.

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.

In vivo and in vitro biocompatibility study of MnFe2O4 and Cr2Fe6O12 as photosensitizer for photodynamic therapy and drug delivery of anti-cancer drugs.

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.

Magnetic nanoparticles decorated with PEGylated curcumin as dual targeted drug delivery: Synthesis, toxicity and biocompatibility study.

The problems associated with hydrophobic anticancer drugs are among the most important challenges to achieve efficient therapeutics for cancer treatment. In this study, PEGylated curcumin was used as the surface modification of magnetic nanoparticles (MNP@PEG-Cur) in order to simultaneously take advantage of magnetic targeting characteristic of nanoparticles and PEG conjugated drug. Curcumin was conjugated through EDC/NHS chemistry to the PEG hydroxyl functional groups, and then physically decorated on the surface of magnetic nanoparticles (MNP). The analysis of the conjugate and nanoparticles by FT-IR, 1HNMR, FE-SEM, TEM, EDX, TGA and VSM confirmed the successful synthesis and proper physicochemical properties of MNP@PEG-Cur nanoparticles. The carrier showed pH dependent drug release profile with higher drug release at acidic media (pH = 5.4) compared to neural condition (pH = 7.4). In addition, LD50 and hemolysis assay confirmed the biocompatibility of MNP@PEG-Cur. The cell viability assay also revealed that neither carrier, nor curcumin-loaded nanoparticles are cytotoxic at physiologic pH (7.4).

In vivo study of mPEG-PCL as a nanocarriers for anti-inflammatory drug delivery of simvastatin.

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.

Amphiphilic Y shaped miktoarm star copolymer for anticancer hydrophobic and hydrophilic drugs codelivery: Synthesis, characterization, in vitro, and in vivo biocompatibility study.

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.

AUP1 (Ancient Ubiquitous Protein 1) Is a Key Determinant of Hepatic Very-Low-Density Lipoprotein Assembly and Secretion.

OBJECTIVE: AUP1 (ancient ubiquitous protein 1) is an endoplasmic reticulum-associated protein that also localizes to the surface of lipid droplets (LDs), with dual role in protein quality control and LD regulation. Here, we investigated the role of AUP1 in hepatic lipid mobilization and demonstrate critical roles in intracellular biogenesis of apoB100 (apolipoprotein B-100), LD mobilization, and very-low-density lipoprotein (VLDL) assembly and secretion. APPROACH AND RESULTS: siRNA (short/small interfering RNA) knockdown of AUP1 significantly increased secretion of VLDL-sized apoB100-containing particles from HepG2 cells, correcting a key metabolic defect in these cells that normally do not secrete much VLDL. Secreted particles contained higher levels of metabolically labeled triglyceride, and AUP1-deficient cells displayed a larger average size of LDs, suggesting a role for AUP1 in lipid mobilization. Importantly, AUP1 was also found to directly interact with apoB100, and this interaction was enhanced with proteasomal inhibition. Knockdown of AUP1 reduced apoB100 ubiquitination, decreased intracellular degradation of newly synthesized apoB100, and enhanced extracellular apoB100 secretion. Interestingly, the stimulatory effect of AUP1 knockdown on VLDL assembly was reminiscent of the effect previously observed after MEK-ERK (mitogen-activated protein kinase kinase-extracellular signal-regulated kinase) inhibition; however, further studies indicated that the AUP1 effect was independent of MEK-ERK signaling. CONCLUSIONS: In summary, our findings reveal an important role for AUP1 as a regulator of apoB100 stability, hepatic LD metabolism, and intracellular lipidation of VLDL particles. AUP1 may be a crucial factor in apoB100 quality control, determining the rate at which apoB100 is degraded or lipidated to enable VLDL particle assembly and secretion.

Complex role of autophagy in regulation of hepatic lipid and lipoprotein metabolism.

Discovering new therapeutic interventions to treat lipid and lipoprotein disorders is of great interest and the discovery of autophagy as a regulator of lipid metabolism has opened up new avenues for targeting modulators of this pathway. Autophagy is a degradative process that targets cellular components to the lysosome and recent studies have indicated a role for autophagy in regulating hepatic lipid metabolism (known as lipophagy) as well as lipoprotein assembly. Autophagy directly targets apolipoprotein B-100 (apoB100), the structural protein component of very low-density lipoproteins (VLDLs), and further targets lipid droplets (LDs), the cellular storage for neutral lipids. Autophagy thus plays a complex and dual role in VLDL particle assembly by regulating apoB100 degradation as well as aiding the maturation of VLDL particles by hydrolyzing lipid from LDs. The purpose of this article is to review our current understanding of molecular and cellular mechanisms mediating authophagic control of hepatic lipid biogenesis and VLDL production as well as dysregulation in insulin resistance and dyslipidemia.