Nanoparticle-mediated gene delivery of TRAIL to resistant cancer cells: A review.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), also known as APO2L, has emerged as a highly potential anticancer agent because of its capacity to effectively trigger apoptosis in tumor cells by specifically binding to either of its death receptors (DR4 or DR5) while having no adverse effects on normal cells. Nevertheless, its practical use has been hindered by its inefficient pharmacokinetics characteristics, the challenges involved in its administration and delivery to targeted cells, and the resistance exhibited by most cancer cells towards TRAIL. Gene therapy, as a promising approach would be able to potentially circumvent TRAIL-based cancer therapy challenges mainly through localized TRAIL expression and generating a bystander impact. Among different strategies, using nanoparticles in TRAIL gene delivery allows for precise targeting, and overcoming TRAIL resistance by combination therapy. In this review, we go over potential mechanisms by which cancer cells achieve resistance to TRAIL and provide an overview of different carriers for delivering of the TRAIL gene to resistant cancer cells, focusing on different types of nanoparticles utilized in this context. We will also explore the challenges, and investigate future perspectives of this nanomedicine approach for cancer therapy.

Advances in ionic liquid-based antimicrobial wound healing platforms.

Wound infections, marked by the proliferation of microorganisms at surgical sites, necessitate the development of innovative wound dressings with potent bactericidal properties to curb microbial growth and prevent bacterial infiltration. This study explores the recent strides in utilizing ionic liquid-based polymers as highly promising antimicrobial agents for advanced wound healing applications. Specifically, cationic polymers containing quaternary ammonium, imidazolium, guanidinium, pyridinium, triazolium, or phosphonium groups have emerged as exceptionally effective antimicrobial compounds. Their mechanism of action involves disrupting bacterial membranes, thereby preventing the development of resistance and minimizing toxicity to mammalian cells. This comprehensive review not only elucidates the intricate dynamics of the skin's immune response and the various stages of wound healing but also delves into the synthesis methodologies of ionic liquid-based polymers. By spotlighting the practical applications of antimicrobial wound dressings, particularly those incorporating ionic liquid-based materials, this review aims to lay the groundwork for future research endeavors in this burgeoning field. Through a nuanced examination of these advancements, this article seeks to contribute to the ongoing progress in developing cutting-edge wound healing platforms that can effectively address the challenges posed by microbial infections in surgical wounds.

Engineered Tissues: A Bright Perspective in Urethral Obstruction Regeneration.

Impact Statement The current article examines urethral reconstruction on three fronts: presently available grafts, clinical trials, and preclinical studies. In this context, studies have focused on various types of biomaterial grafts, including natural, synthetic, and decellularized, combined with or without cells or growth factors, aiming to improve outcomes at both clinical and pre-clinical stages. Subsequently, four stages in the commercialization regulatory pathway in urethra engineering were examined, focusing on the commercialization challenges, particularly those associated with urethral products. Finally, the forthcoming challenges in urethra engineering and potential solutions for its enhancement have been explored. [Figure: see text].

Poly-ε-caprolactone (PCL)/poly-l-lactic acid (PLLA) nanofibers loaded by nanoparticles-containing TGF-ß1 with linearly arranged transforming structure as a scaffold in cartilage tissue engineering.

This study aimed to present a novel three-dimensional nanocomposite scaffold using poly-ε-caprolactone (PCL), containing transforming growth factor-beta 1 (TGF-ß1)-loaded chitosan-dextran nanoparticles and poly-l-lactic acid (PLLA), to make use of nanofibers and nanoparticles simultaneously. The electrospinning method fabricated a bead-free semi-aligned nanofiber composed of PLLA, PCL, and chitosan-dextran nanoparticles containing TGF-ß1. A biomimetic scaffold was constructed with the desired mechanical properties, high hydrophilicity, and high porosity. Transmission electron microscopy findings showed a linear arrangement of nanoparticles along the core of fibers. Based on the results, burst release was not observed. The maximum release was achieved within 4 days, and sustained release was up to 21 days. The qRT-PCR results indicated an increase in the expression of aggrecan and collagen type Ι genes compared to the tissue culture polystyrene group. The results indicated the importance of topography and the sustained release of TGF-ß1 from bifunctional scaffolds in directing the stem cell fate in cartilage tissue engineering.

Prevention of peritoneal adhesions formation by core-shell electrospun ibuprofen-loaded PEG/silk fibrous membrane.

Adhesion bands are pathological fibrous tissues that create in the middle of tissues and organs, often reasons of intestinal obstruction, and female infertility. Here, we explored the anti-adhesive and inflammatory capacities of PEG/silk and Ibuprofen-loaded PEG/Silk core-shell nanofibrous membranes, respectively. The ibuprofen-loaded Silk Fibroin-Poly ethylene Glycol (SF-PEG) core-shell membrane was fabricated by electrospinning and considered in terms of morphology, surface wettability, drug release, and degradation. To reveal the membrane capability for adhesion bands inhibition, the membrane was stitched among the abdominal partition and peritoneum and then evaluated using two scoring adhesion systems. According to results, the fibrous membrane hindered cell proliferation, and the scoring systems and pathology showed that in a rat model, Ibuprofen-loaded PEG/Silk core-shell membrane caused a lightening in post-operative adhesion bands and the low-grade inflammatory reaction in animal models. Collectively, we fabricated new ibuprofen-loaded PEG/SF membranes with anti-adhesion and anti-inflammation properties. Moreover, this core-shell electrospun fibrous membrane has not even now been used to prevent peritendinous adhesion generation.

Surface modification of neurotrophin-3 loaded PCL/chitosan nanofiber/net by alginate hydrogel microlayer for enhanced biocompatibility in neural tissue engineering.

This study prepared a novel three-dimensional nanocomposite scaffold by the surface modification of PCL/chitosan nanofiber/net with alginate hydrogel microlayer, hoping to have the privilege of both nanofibers and hydrogels simultaneously. Bead free randomly oriented nanofiber/net (NFN) structure composed of chitosan and polycaprolactone (PCL) was fabricated by electrospinning method. The low surface roughness, good hydrophilicity, and high porosity were obtained from the NFN structure. Then, the PCL/chitosan nanofiber/net was coated with a microlayer of alginate containing neurotrophin-3 (NT-3) and conjunctiva mesenchymal stem cells (CJMSCs) as a new stem cell source. According to the cross-sectional FESEM, the scaffold shows a two-layer structure with interconnected pores in the range of 20 µm diameter. The finding revealed that the surface modification of nanofiber/net by alginate hydrogel microlayer caused lower inflammatory response and higher proliferation of CJMSCs than the unmodified scaffold. The initial burst release of NT-3 was 69% in 3 days which followed by a sustained release up to 21 days. The RT-PCR analysis showed that the expression of Nestin, MAP-2, and ß-tubulin III genes were increased 6, 5.4, and 8.8-fold, respectively. The results revealed that the surface-modified biomimetic scaffold possesses enhanced biocompatibility and could successfully differentiate CJMSCs to the neuron-like cells.

Preparation and characterization of PEGylated multiwall carbon nanotubes as covalently conjugated and non-covalent drug carrier: A comparative study.

In this study, PEGylated multiwall carbon nanotubes (MWNTs)-based drug delivery system was developed. Ibuprofen as a model drug was loaded by physical and chemical method. The surface functionalization of nanotubes was carried out by enrichment of acylated groups. In order to synthesis PEGylated MWNTs, hydrophilic diamino-polyethylene glycol was covalently linked to the MWNTs surface via amidation reaction. Finally, ibuprofen was chemically and physically loaded on the PEGylated MWNTs. The resultants were characterized by FTIR, AFM, and DLS techniques. Cytotoxicity of PEGylated MWNTs were examined by MTT assay and the results revealed that PEG functionalized nanotubes did not show significant detrimental effects on the viability of L929 Cells. The percent of drug loading for chemically and physically drug payload carrier were determined to be 52.5% and 38%, respectively. The release of ibuprofen from covalently conjugated and non-covalent drug loaded PEGylated MWNTs at pH=7.4, and 5.3 were investigated, as well. From the results, it was found that chemically loaded MWNTs showed much sustained release behavior compared to the physically loaded one, especially at pH=5.3. The kinetic of drug release was also investigated. The results strongly suggest that the chemically conjugated PEGylated MWNTs could be used as controlled release system for various drugs.

Synthesis and characterization of dextran coated magnetite nanoparticles for diagnostics and therapy.

INTRODUCTION: Expansion of efficacious theranostic systems is of pivotal significance for medicine and human healthcare. Magnetic nanoparticles (MNPs) are known as drug delivery system and magnetic resonance imaging (MRI) contrast agent. MNPs as drug carriers have attracted significant attention because of the delivery of drugs loaded onto MNPs to solid tumors, maintaining them in the target site by an external electromagnetic field, and subsequently releasing drugs in a controlled manner. On the other hand, it is believed that MNPs possess high potential as MRI contrast agents. The aim of this work was to payload curcumin into dextran coated MNPs and investigate their potential as theranostic systems for controlled drug delivery and MRI imaging. METHODS: MNPs were synthesized as a core and coated with dextran as polymeric shell to provide steric stabilization. Curcumin as anticancer drug was selected to be loaded into NPs. To characterize the synthesized NPs, various techniques (e.g., DLS, FESEM, FT-IR, XRD, and VSM) were utilized. In vitro drug release of curcumin was evaluated at 37˚C at the pH value of 5.4 and 7.4.The feasibility of employment of dextran coated MNPs as MRI contrast agents were also studied. RESULTS: Formulations prepared from dextran coated MNPs showed high loading (13%) and encapsulation efficiency (95%). In vitro release study performed in the phosphate-buffered saline (PBS, pH= 7.4, 5.4) revealed that the dextran coated MNPs possess sustained release behavior at least for 4 days with the high extent of drug release in acidic media. Vibrating sample magnetometer (VSM) analysis proved the superparamagnetic properties of the dextran coated MNPs with relatively high-magnetization value indicating that they were sufficiently sensitive to external magnetic fields as magnetic drug carriers. Furthermore, dextran coated MNPs exhibited high potential as T2 contrast agents for MRI. CONCLUSION: Based on our findings, we propose the dextran coated MNPs as promising nanosystem for the delivery of various drugs such as curcumin and MRI contrast agent.