Use of single-chain antibody derivatives for targeted drug delivery

Single-chain antibodies (scFvs), which contain only the variable domains of full-length antibodies, are relatively small molecules that can be used for selective drug delivery. In this review, we discuss how scFvs help improve the specificity and efficiency of drugs. Small interfering RNA (siRNA) delivery using scFv-drug fusion peptides, siRNA delivery using scFv-conjugated nanoparticles, targeted delivery using scFv-viral peptide-fusion proteins, use of scFv in fusion with cell-penetrating peptides for effective targeted drug delivery, scFv-mediated targeted delivery of inorganic nanoparticles, scFv-mediated increase of tumor killing activity of granulocytes, use of scFv for tumor imaging, site-directed conjugation of scFv molecules to drug carrier systems, use of scFv to relieve pain and use of scFv for increasing drug loading efficiency are among the topics that are discussed here. © 2016, University of Michigan. All rights reserved

A novel diblock copolymer of (monomethoxy poly [ethylene glycol]-oleate) with a small hydrophobic fraction to make stable micelles/polymersomes for curcumin delivery to cancer cells

Curcumin is a potent natural anticancer agent, but its effectiveness is limited by properties such as very low solubility, high rate of degradation, and low rate of absorption of its hydrophobic molecules in vivo. To date, various nanocarriers have been used to improve the bioavailability of this hydrophobic biomaterial. This study investigates the encapsulation of curcumin in a novel nanostructure of monomethoxy poly(ethylene glycol)-oleate (mPEG-OA) and its anticancer effect. Tests were done to determine the critical micelle concentration (CMC), encapsulation efficiency, drug-loading efficiency, and cytotoxicity (against U87MG brain carcinoma cells and HFSF-PI3 cells as normal human fibroblasts) of some nanodevice preparations. The results of fluorescence microscopy and cell-cycle analyses indicated that the in vitro bioavailability of the encapsulated curcumin was significantly greater than that of free curcumin. Cytotoxicity evaluations showed that half maximal inhibitory concentrations of free curcumin and curcumin-loaded mPEG-OA for the U87MG cancer cell line were 48 μM and 24 μM, respectively. The Annexin-V-FLUOS assay was used to quantify the apoptotic effect of the prepared nanostructures. Apoptosis induction was observed in a dose-dependent manner after curcumin-loaded mPEG-OA treatments. Two common self-assembling structures, micelles and polymersomes, were observed by atomic force microscopy and dynamic light scat­tering, and the abundance of each structure was dependent on the concentration of the diblock copolymer. The mPEG-OA micelles had a very low CMC (13.24 μM or 0.03 g/L). Moreover, atomic force microscopy and dynamic light scattering showed that the curcumin-loaded mPEG-OA polymersomes had very stable structures, and at concentrations 1,000 times less than the CMC, at which the micelles disappear, polymersomes were the dominant structures in the dispersion with a reduced size distribution below 150 nm. Overall, the results from these tests revealed that this nanocarrier can be considered as an appropriate drug delivery system for delivering curcumin to cancer cells. © 2014 Erfani-Moghadam et al

Synthesis of doxorubicin-loaded PBMA-b-POEGMA micelles and assessment of its anticancer activity against breast cancer cells (4T1)

Doxorubicin (DOX) is a chemotherapy drug that possesses many side effects. This study aimed to synthesize PBMA-b-POEGMA poly (butyl methacrylate)-b-poly (oligo ethylene glycol methacrylate) diblock copolymer as a nanocarrier for loading of DOX, promoting anticancer efficacy of the drug, and decreasing its side effects. Hence, PBMA-b-POEGMA diblock copolymer was first synthesized by the RAFT method and then DOX encapsulated into the micellar nanocarrier. Self-assembly behavior of copolymers and physicochemical/biological properties of nanocarriers were assessed. DLS and TEM images showed nanocarriers possessed spherical-uniform structure with the mean size and polydispersity of 27 ± 1.34 nm and 0.13 ± 0.21 for blank-micelles as well as, 45 ± 2.32 nm and 0.18 ± 0.18 for DOX-loaded micelles, respectively. Synthesized micelles also provided high drug encapsulation efficiency (>80%) with a drug loading content of 4.53%. Moreover, the maximum released amount of drug was reported at 69%, with the Korsmeyer-Peppas model, as a more suitable model to describe the release behavior of DOX from nanocarriers. Biologically, block copolymers were biocompatible against COS-7 and 4T1 cell lines, in addition, free-DOX showed higher cytotoxicity than DOX-loaded micelles. Furthermore, 0.5 μg/mL concentration of drug-loaded micelle led to growth inhibition of more than 60% of cancerous cells, during 48 h, so that higher level of cellular uptake of drug and apoptosis in 4T1 cells was induced by drug-loaded micelles. © 2022 Wiley Periodicals LLC

Synthesis, spectroscopic characterization, molecular docking, as well as in vitro cytotoxicity of calcium-sulfasalazine complex

With the growing resistance of the bacterial strains resistant against antibiotics like sulfasalazine (SSZ) drug which has been of a great concern recently, bioactive metal complexation with an antibacterial agent �sulfasalazine� could be a potential solution in order to enhance the biocidal property of the drug. Herein, Calcium (II) sulfasalazine complex was experimentally synthesized and characterized by using infrared (IR) and UV�vis spectroscopic techniques. The complex was modeled using density functional theory (DFT) and time-dependent density functional theory (TD-DFT) calculations in order to analyze its electronic and optical properties and thermodynamic parameters in gas and PCM (ethanol) environments and compare these results with those of the experimental results where relevant. Cell toxicity assay (MTT) indicated that the half-maximal inhibitory concentrations (IC50) of SSZ and its combination with Ca were has no significant toxicity at concentrations below 650 µM in HDF cell lines. © 2022 Elsevier B.V

Cationic vesicles for efficient shRNA transfection in the MCF-7 breast cancer cell line

Pardis Mokhtary,1,2 Bita Javan,1,3 Mahrokh Sharbatkhari,4 Alireza Soltani,5 Vahid Erfani-Moghadam1,2 1Medical Cellular and Molecular Research Center, Golestan University of Medical Sciences, Gorgan, Iran; 2Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran; 3Department of Molecular Medicine, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran; 4R&D Section, Arya Tina Gene Biopharmaceutical Company, Gorgan, Iran; 5Golestan Rheumatology Research Center, Golestan University of Medical Sciences, Gorgan, Iran Introduction: Novel and safe delivery solutions for RNAi therapeutics are essential to obtain the full potential of cancer gene therapy. Methods: In this study, cationic vesicular nanocarrier was applied for delivering lnc urothelial carcinoma-associated 1 (lnc UCA1) shRNA expression vector to MCF-7 cells. The physicochemical characteristics, cytotoxicity, and transfection efficiency of cationic vesicles prepared from various molar ratios of amphiphilic surfactant Tween 80 (T), squalene (S), cationic charge lipid didodecyldimethylammonium bromide, and polyethylenimine were investigated. The particle sizes of the vesicles in the nanosize range were determined by dynamic light scattering and transmission electron microscopy. Results: Gel protection assay with agarose gel electrophoresis showed cationic vesicles can protect the shRNA plasmid from DNase 1 enzyme. 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium, inner salt result showed no significant cytotoxicity was caused in MCF-7 cancer cell line by (T:S):polyethylenimine cationic vesicles. 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium, inner salt assay, fluorescence microscope images, and flow cytometry analyses confirmed that (T:S)1,040 µM with 4.3 µg/mL of PEI vesicles provided effective transfection without significant cytotoxicity. Furthermore, we found efficient UCA1 shRNA transfection and significant (P<0.05) cell cycle arrest and apoptosis in MCF-7 cancer cells. Conclusion: The novel nonviral vesicular nanocarrier, (T:S)1,040 µM with 4.3 µg/mL of PEI, might be safe and efficient for cancer gene therapy and can be used in further in vitro and in vivo studies. Keywords: cationic vesicles, shRNA, UCA1, apoptosis, gene deliver

Cationic vesicles for efficient shRNA transfection in the MCF-7 breast cancer cell line

Introduction: Novel and safe delivery solutions for RNAi therapeutics are essential to obtain the full potential of cancer gene therapy. Methods: In this study, cationic vesicular nanocarrier was applied for delivering lnc urothelial carcinoma-associated 1 (lnc UCA1) shRNA expression vector to MCF-7 cells. The physicochemical characteristics, cytotoxicity, and transfection efficiency of cationic vesicles prepared from various molar ratios of amphiphilic surfactant Tween 80 (T), squalene (S), cationic charge lipid didodecyldimethylammonium bromide, and polyethylenimine were investigated. The particle sizes of the vesicles in the nanosize range were determined by dynamic light scattering and transmission electron microscopy. Results: Gel protection assay with agarose gel electrophoresis showed cationic vesicles can protect the shRNA plasmid from DNase 1 enzyme. 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium, inner salt result showed no significant cytotoxicity was caused in MCF-7 cancer cell line by (T:S):polyethylenimine cationic vesicles. 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium, inner salt assay, fluorescence microscope images, and flow cytometry analyses confirmed that (T:S)1,040 μM with 4.3 μg/mL of PEI vesicles provided effective transfection without significant cytotoxicity. Furthermore, we found efficient UCA1 shRNA transfection and significant (P<0.05) cell cycle arrest and apoptosis in MCF-7 cancer cells. Conclusion: The novel nonviral vesicular nanocarrier, (T:S)1,040 μM with 4.3 μg/mL of PEI, might be safe and efficient for cancer gene therapy and can be used in further in vitro and in vivo studies

A novel diblock copolymer of (monomethoxy poly [ethylene glycol]-oleate) with a small hydrophobic fraction to make stable micelles/polymersomes for curcumin delivery to cancer cells

Vahid Erfani-Moghadam,1,6 Alireza Nomani,2 Mina Zamani,3 Yaghoub Yazdani,4 Farhood Najafi,5 Majid Sadeghizadeh1,3 1Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran; 2Department of Pharmaceutics, Faculty of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran; 3Department of Genetics, Faculty&nbsp;of&nbsp;Biological Sciences, Tarbiat&nbsp;Modares University, Tehran, Iran; 4Infectious Diseases Research Center and Laboratory Science Research Center, Golestan University of Medical Sciences, Gorgan, Golestan, Iran; 5Department of Resin and Additives, Institute for Color Science and&nbsp;Technology, Tehran, Iran; 6Department of Biotechnology, Faculty of Advanced Medical Technology, Golestan University of&nbsp;Medical Sciences, Gorgan, Iran Abstract: Curcumin is a potent natural anticancer agent, but its effectiveness is limited by properties such as very low solubility, high rate of degradation, and low rate of absorption of its hydrophobic molecules in vivo. To date, various nanocarriers have been used to improve the bioavailability of this hydrophobic biomaterial. This study investigates the encapsulation of curcumin in a novel nanostructure of monomethoxy poly(ethylene glycol)-oleate (mPEG-OA) and its anticancer effect. Tests were done to determine the critical micelle concentration (CMC), encapsulation efficiency, drug-loading efficiency, and cytotoxicity (against U87MG brain carcinoma cells and HFSF-PI3 cells as normal human fibroblasts) of some nanodevice preparations. The results of fluorescence microscopy and cell-cycle analyses indicated that the&nbsp;in vitro bioavailability of the encapsulated curcumin was significantly greater than that of free curcumin. Cytotoxicity evaluations showed that half maximal inhibitory concentrations of free curcumin and curcumin-loaded mPEG-OA for the U87MG cancer cell line were 48 &micro;M and 24 &micro;M, respectively. The Annexin-V-FLUOS assay was used to quantify the apoptotic effect of the prepared nanostructures. Apoptosis induction was observed in a dose-dependent manner after curcumin-loaded mPEG-OA treatments. Two common self-assembling structures, micelles and polymersomes, were observed by atomic force microscopy and dynamic light scattering, and the abundance of each structure was dependent on the concentration of the diblock copolymer. The mPEG-OA micelles had a very low CMC (13.24 &micro;M or 0.03 g/L). Moreover, atomic force microscopy and dynamic light scattering showed that the curcumin-loaded mPEG-OA polymersomes had very stable structures, and at concentrations 1,000&nbsp;times less than the CMC, at which the micelles disappear, polymersomes were the dominant structures in the dispersion with a reduced size distribution below 150 nm. Overall, the results from these tests revealed that this nanocarrier can be considered as an appropriate drug delivery system for delivering curcumin to cancer cells. Keywords: anticancer agent, nanocarrier, encapsulation, bioavailability, apoptosis, critical micelle concentratio