Search

Background Poly (β-amino Ester) nanocarriers show promise for gene therapy, but their effectiveness can be limited by the environment within the body. This study aims to understand how common cell culture media components affect optimized PBAE nanocarrier performance in gene delivery. Methods Optimized PBAE was synthesized based on Michael addition reaction and characterized by different assays, this study employed techniques like DLS and TEM to characterize PBAE nanocarriers, followed by cellular uptake analysis (flow cytometry and confocal imaging) and evaluation of gene expression under different polymer/DNA ratio ratios and media conditions. Results The nanocarriers exhibited size under 200 nm and surface positive charge, with high encapsulation efficiency (up to 95%). Cellular uptake, transfection efficiency, and cytotoxicity were evaluated. Flow cytometry analysis revealed high cellular uptake (over 77% at 1 hour and up to 95% after 3 hours) and good viability. Transfection efficiency reached up to 80% with 2 μg DNA, particularly at weight ratios of 60 and 90. Conclusion The study also identified factors affecting transfection efficiency, including serum concentration and antibiotics in the culture medium, highlighting the importance of optimizing these conditions for future applications. Plain Language Summary Our study focused on a new way to deliver medicine directly to cells using tiny particles called nanocarriers. These tiny particles are made from a special material called PBAE. Our study found that certain things around these nanocarriers, like antibiotics and high levels of a substance in the cell medium, can make it harder for the medicine to get into the cells. We also found that while the PBAE material is safe on its own, it can become more harmful when used in the nanocarriers at high amounts. By figuring out the best conditions for these nanocarriers, we hope to make gene therapy, a treatment for diseases like cancer, work better and be safer. GRAPHICAL ABSTRACT [ABSTRACT FROM AUTHOR] more...

Clinical advances in genetically modified immune cell therapies, such as chimeric antigen receptor T cell therapies, have raised hope for cancer treatment. The majority of these biotechnologies are based on viral methods for ex vivo genetic modification of the immune cells, while the non-viral methods are still in the developmental phase. Nanocarriers have been emerging as materials of choice for gene delivery to immune cells. This is due to their versatile physicochemical properties such as large surface area and size that can be optimized to overcome several practical barriers to successful gene delivery. The in vivo nanocarrier-based gene delivery can revolutionize cell-based cancer immunotherapies by replacing the current expensive autologous cell manufacturing with an off-the-shelf biomaterial-based platform. The aim of this research is to review current advances and strategies to overcome the challenges in nanoparticle-based gene delivery and their impact on the efficiency, safety, and specificity of the process. The main focus is on polymeric and lipid-based nanocarriers, and their recent preclinical applications for cancer immunotherapy. [ABSTRACT FROM AUTHOR] more...

A pH-sensitive shell-sheddable magnetic nanocarrier was prepared based on Fe3O4@SiO2 nanoparticles coated with polyethyleneimine (PEI) and polyethyleneglycol (PEG). The PEI was coated on Fe3O4@SiO2 nanoparticles through an electrostatic attraction and the PEG chains were connected to the PEI via pH-sensitive benzoicimine bonds. The synthesized products and final nanocarrier were characterized with FT-IR, 1H NMR, dynamic light scattering (DLS), zeta-potential, TEM, and vibrating sample magnetometer (VSM). The PEI, as a middle layer, was used to load the curcumin (an anticancer drug) via van der Waals interactions and the shedding of PEG as a hydrophilic corona at the tumor pH (acidic) could induce the release of the drug. The curcumin loading content was found to be ~15% and curcumin-loaded magnetic nanoparticles (C-LMNs) showed more triggered release at the tumor pH (5.6) than physiological pH (7.4). In comparison to pure magnetic nanoparticles (MNs), the C-LMNs showed more cytotoxicity to human prostate cancer cell (PC-3) and also resulted in an increased rate of late apoptotic/necrotic PC-3 cells, assessed by flow cytometry analysis. In conclusion, the C-LMN as pH- and magnetic responsive nano-carrier showed good potential for targeted curcumin delivery in therapy of prostate cancer. [ABSTRACT FROM AUTHOR] more...

Iron oxide nanoparticle (IONPs) have become a subject of interest in various biomedical fields due to their magnetism and biocompatibility. They can be utilized as heat mediators in magnetic hyperthermia (MHT) or as contrast media in magnetic resonance imaging (MRI), and ultrasound (US). In addition, their high drug-loading capacity enabled them to be therapeutic agent transporters for malignancy treatment. Hence, smartening them allows for an intelligent controlled drug release (CDR) and targeted drug delivery (TDD). Smart magnetic nanoparticles (SMNPs) can overcome the impediments faced by classical chemo-treatment strategies, since they can be navigated and release drug via external or internal stimuli. Recently, they have been synchronized with other modalities, e.g., MRI, MHT, US, and for dual/multimodal theranostic applications in a single platform. Herein, we provide an overview of the attributes of MNPs for cancer theranostic application, fabrication procedures, surface coatings, targeting approaches, and recent advancement of SMNPs. Even though MNPs feature numerous privileges over chemotherapy agents, obstacles remain in clinical usage. This review in particular covers the clinical predicaments faced by SMNPs and future research scopes in the field of SMNPs for cancer theranostics. [ABSTRACT FROM AUTHOR] more...

Keywords: biomolecular engineering; early detection; molecular biomedicine; molecular diagnosis; prognosis EN biomolecular engineering early detection molecular biomedicine molecular diagnosis prognosis 1 4 4 05/27/20 20200601 NES 200601 Introduction For the past nine years, Royan Institute (Tehran, Iran) has held annual international summer schools to educate and promote key basic and applied concepts regarding stem cells, cancer, personalized medicine, tissue engineering, and developmental biology. The speakers discussed genome-editing technologies, gene- and RNA interference (RNAi) therapies, cancer vaccines, and molecular diagnosis via biomarkers and biosensors. Overall, the summer school highlighted how combination of molecular diagnosis and molecular therapy can provide higher success rates in disease treatment in the near future. Viral and Non-Viral Gene Therapy Piter Bosma explained that gene therapy, that is, delivering genetic material to treat diseases, is accomplished through non-viral or viral delivery systems. [Extracted from the article] more...

Magnetic molecularly imprinted polymers have been synthesized for the selective preconcentration and trace determination of lamotrigine (LTG) in urine and plasma samples. The magnetic nanoparticles were modified by tetraethyl orthosilicate and 3-methacryloxypropyl trimethoxysilane before imprinting. The magnetic molecularly imprinted polymers were prepared via surface molecular imprinting technique, using Fe3O4 as a magnetic component, LTG as template molecule, methacrylic acid as a functional monomer, ethylene glycol dimethacrylate as a cross-linker, and 2,2′-azobisisobutyronitrile as a radical initiator in methanol/acetonitrile (50:50, v/v) as the porogen. The obtained sorbent was characterized using scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, and thermal analysis. Separation of the sorbent from the sample solution was simply achieved by applying an external magnetic field. Determination of the extracted drug was performed by high-performance liquid chromatography with UV detection. Under the optimum extraction conditions, the method detection limits were 0.7 μg/L (based on S/ N of 3) for urine samples and 0.5 μg/L for plasma samples. A linear dynamic range of 1-1000 μg/L was obtained for LTF in plasma and urine samples. Finally, the applicability of the proposed method was evaluated by extraction and determination of LTG in urine and plasma samples. [ABSTRACT FROM AUTHOR] more...

A molecular-imprinted polymer nanoparticles (MIP-NP) for the selective preconcentration of 2,4-dichlorophenoxyacetic acid (2,4-D) is described. It was obtained by precipitation polymerization from methacrylic acid (the functional monomer), ethylene glycol dimethacrylate (the cross-linker), 2,2'-azobisisobutyronitrile (the initiator) and 2,4-D (the template molecule) in acetonitrile solution. The MIP-NPs were characterized by thermogravimetric analysis, and by scanning electron microscopy. Imprinted 2,4-D molecules were removed from the polymeric structure using acetic acid in methanol (15:85 v/v %) as the eluting solvent. The sorption and desorption process occur within 10 min and 15 min, respectively. The maximum sorbent capacity of the molecular imprinted polymer is 89.2 mg g(-1). The relative standard deviation and limit of detection for water samples by introduced selective solid phase extraction were 4.2% and 1.25 μg L(-1), and these data for urine samples were 4.7% and 1.80 μg L(-1), respectively. The method was applied to the determination of 2,4-D in the urine and different water samples. more...