Biology subjects

Attia, M. F.

Publications and source records attributed to Attia, M. F..

4 recordsLinked to original sources

bioRxiv2025

Enhanced Wound Healing and Anti-Inflammatory Effects of Vitamin C-Loaded Hyaluronic Acid/Collagen Scaffolds in Preclinical Rat Models

Wound healing is a complex biological process critical for restoring skin integrity after injury. However, chronic wounds present significant clinical challenges due to persistent inflammation, disrupted collagen synthesis, and susceptibility to infection. Bioactive scaffolds have emerged as promising therapeutic strategies to enhance tissue regeneration by modulating cellular behavior and extracellular matrix (ECM) dynamics. This study explores a hyaluronic acid-collagen (HyCol) scaffold enriched with vitamin C (VC), producing (VC-HyCol) to improve wound healing in preclinical rat models. Hyaluronic acid and collagen, key ECM components, provide structural and biochemical support, while vitamin C acts as both a collagen biosynthesis cofactor and an antioxidant to counteract oxidative stress. The scaffold was designed to emulate the native ECM microenvironment, facilitating fibroblast proliferation, keratinocyte migration, and angiogenesis. Physicochemical characterization, biocompatibility assessments, and in vivo wound healing experiments were performed to evaluate its therapeutic efficacy. Results demonstrated that the incorporation of vitamin C significantly enhanced fibroblast activity, reduced inflammatory markers, and accelerated tissue regeneration compared to control groups. Histological and molecular analyses further confirmed enhanced collagen deposition and neovascularization, indicating faster and more organized wound repair. These findings highlight the potential of this multifunctional scaffold as an advanced wound dressing, with significant implications for regenerative medicine and clinical wound management. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=116 SRC="FIGDIR/small/665568v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@d8d248org.highwire.dtl.DTLVardef@d58e05org.highwire.dtl.DTLVardef@5f210eorg.highwire.dtl.DTLVardef@17354b1_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2025

High-integrity nanoemulsions formulation of resiquimod (R848) enhances stability and delivery for triple negative breast cancer immunotherapy

Triple-negative breast cancer (TNBC) poses significant clinical challenges due to its high heterogeneity, with multiple subtypes exhibiting distinct molecular characteristics and treatment responses. The development of resistance to chemotherapy and targeted therapies remains a major obstacle, and identifying reliable biomarkers to predict therapeutic response continues to be challenging. This study aims to enhance the delivery of the immunostimulant Toll-like receptor 7/8 (TLR7/8) agonist resiquimod (R848) using a safe and highly integrated nanoemulsions (NEs) formulation, providing effective and reliable immunotherapy. A series of NEs were prepared and optimized with and without the reactive lipophilic compound ricinoleic acid. Neutral and negatively charged NE formulations encapsulating R848 were compared. The physicochemical properties and in vitro delivery of resiquimod into RAW 264.7 macrophages and 4T1 TNBC cell line models were studied. Both R848-loaded NE formulations exhibited prolonged shelf-life stability with minimal protein binding. Incorporating small portions of ricinoleic acid into the formulation (negatively charged NEs) slowed drug release and improved physical properties and overall delivery compared to ricinoleic-free formulations, likely due to its interaction with the drug. Cytotoxicity and cellular uptake studies were conducted on both NE models, showing localization in the macrophage cell membrane and 4T1 cell cytoplasm. Molecular profiling in 4T1 cells revealed R848-NEs modulated key biomarkers (TLR4/7, Cyclin D1, NF-{kappa}B) while potently inducing autophagy (evidenced by LC3II/p62/Beclin-1 alterations) and PD-L1 upregulation. These dual effects--autophagy-mediated tumor suppression and immune checkpoint modulation--suggest therapeutic synergy between R848-NEs and anti-PD-L1 antibodies, presenting a promising combinatorial strategy for TNBC treatment. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=72 SRC="FIGDIR/small/647265v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@d4daceorg.highwire.dtl.DTLVardef@692daforg.highwire.dtl.DTLVardef@13676d7org.highwire.dtl.DTLVardef@b449fc_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2024

Toward the Clinical Translation of Safe Intravenous Long Circulating Iodinated Lipid Nanoemulsion Contrast Agents for CT Imaging

Current clinical small molecule x-ray CT agents are effective but pose risks such as nephrotoxicity, short blood circulation time, limiting scan durations, potential thyroid impact, and immune responses. These challenges drive the development of kidney-safe x-ray nanoparticle (NP)-based contrast agents (CAs), though translation to clinical practice is hindered by chemical complexities and potential toxicity. We have engineered an intravenous, injectable, and safe blood pool NP-based CT CAs at a clinical-equivalent dose of [~]300 mgI/kg ([~]2 mL/kg), ideal for vascular and hepatic imaging which are limited by clinical agents. Our iodinated lipid nanodroplet emulsions (ILNEs) contrast agent offers high x-ray attenuation thus improved contrast enhancement, extended stability, and exceptional batch-to-batch consistency. It also boasts a straightforward and scalable manufacturing process with minimal protein interaction, prolonged blood residency ([~]4h), and hepatic clearance within 3 days, avoiding nephrotoxicity. Studies in vitro, in mice, and 16.6kg porcine animal model studies confirm its safety, cytocompatibility, and absence of tissue damage. Blood, and thyroid-stimulating hormone (TSH) analyses, and kidney and liver function tests, also support further toxicity evaluations for clinical translation.

bioengineering↗

bioRxiv2023

Enhancing Drug Delivery with Supramolecular Amphiphilic Macrocycle Nanoparticles: Selective Targeting of CDK4/6 Inhibitor Palbociclib to Melanoma

Drug delivery systems based on amphiphilic supramolecular macrocycles have garnered increased attention over the past two decades due to their ability to successfully formulate nanoparticles. Macrocyclic (MC) materials can self-assemble at lower concentrations without the need for surfactants and polymers, but surfactants are required to form and stabilize nanoparticles at higher concentrations. Using MCs to deliver both hydrophilic and hydrophobic guest molecules is advantageous. We developed two novel types of amphiphilic macrocycle nanoparticles (MC NPs) capable of delivering either Nile Red (NR) (a hydrophobic model) or Rhodamine B (RhB) (a hydrophilic model) fluorescent dyes. We extensively characterized the materials using various techniques to determine size, morphology, stability, hemolysis, fluorescence, loading efficiency (LE), and loading capacity (LC). We then loaded the CDK4/6 inhibitor Palbociclib (Palb) into both MC NPs using a solvent diffusion method. This yielded Palb-MC NPs in the size range of 65-90 nm. They exhibited high stability over time and in fetal bovine serum with negligible toxicity against erythrocytes. Cytotoxicity was minimal when tested against RAW macrophages, human fibroblast HDFn, and adipose stromal cells (ASCs) at higher concentrations of MC NPs. Cell viability studies were conducted with different concentrations of MC NPs, Palb-MC NPs, and free Palb against RAW macrophages, human U-87 GBM, and human M14 melanoma cell lines in vitro. Flow cytometry experiments revealed that blank MC NPs and Palb-MC NPs were selectively targeted to melanoma cells, resulting in cell death compared to the other two cell lines. Future work will focus on studying the biological effect of MC NPs including their binding affinity with molecules/receptors expressed on the M14 and other melanoma cell surface by molecular docking simulations. Subsequently, we will evaluate the MCs as a component of combination therapy in a murine melanoma model. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=154 SRC="FIGDIR/small/567974v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@5cddb9org.highwire.dtl.DTLVardef@e0c4e0org.highwire.dtl.DTLVardef@9d6838org.highwire.dtl.DTLVardef@2556b2_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗