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Noureddine, Achraf

Publications and source records attributed to Noureddine, Achraf.

14 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Metallic Cation-Mediated Entrapment of Nucleic Acids on Mesoporous Silica Surface: Application in Castration-Resistant Prostate Cancer

The use of exogenous nucleic acid technologies to modulate aberrant protein expression resulting from genetic mutations is a promising therapeutic approach for the treatment of diseases such as advanced prostate cancer (PC). The promise of nucleic-based therapeutics is dependent on the development of platforms that effectively protect nucleic acids from nuclease degradation and deliver the nucleic acids to the cytosol of target cells. In this work, we present the development of a divalent metal-mediated nucleic acid entrapment strategy with a porous silica matrix. This simple strategy results in efficient loading percentages of both siRNA (>60%) and mRNA (>80%) as well as their release within relevant biological environments (80%). Additionally, our data supports that the current method reduces endosomal entrapment and supports the lipid coating of mesoporous silica nanoparticles (LC-MSNs). Finally, the metal-enhanced nanosystem is assessed for biocompatibility, stability, and circulation within in vitro, ex ovo, and in vivo models of PC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Lipid-coated mesoporous silica nanoparticles for anti-viral applications via delivery of CRISPR-Cas9 ribonucleoproteins

Abstract Emerging and re-emerging viral pathogens present a unique challenge for anti-viral therapeutic development. Anti-viral approaches with high flexibility and rapid production times are essential for combating these high-pandemic risk viruses. CRISPR-Cas technologies have been extensively repurposed to treat a variety of diseases, with recent work expanding into potential applications against viral infections. However, delivery still presents a major challenge for these technologies. Lipid-coated mesoporous silica nanoparticles (LCMSNs) offer an attractive delivery vehicle for a variety of cargos due to their high biocompatibility, tractable synthesis, and amenability to chemical functionalization. Here, we report the use of LCMSNs to deliver CRISPR-Cas9 ribonucleoproteins (RNPs) that target the Niemann–Pick disease type C1 gene, an essential host factor required for entry of the high-pandemic risk pathogen Ebola virus, demonstrating an efficient reduction in viral infection. We further highlight successful in vivo delivery of the RNP-LCMSN platform to the mouse liver via systemic administration.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Sol–Gel‐Based Advanced Porous Silica Materials for Biomedical Applications

Abstract Porous silica‐based materials have burgeoning applications ranging from fillers and additives, to adsorbents, catalysts, and recently therapeutic agents and vaccines in nanomedicine. The preponderance of these materials is made by sol–gel processing wherein soluble silica precursors are reacted to form amorphous networks composed of siloxane bonds. The facile sol–gel approach allows for an unlimited variety of binary tertiary and more complex chemical compositions including organic ligands and networks resulting in so‐called organic–inorganic hybrid materials. Here, a brief review of the recent progress in sol–gel‐derived silica materials prepared as particles, thin films, biosilica/silica bioreplicas (of molecules, cells and organisms), and their related preparation, properties, and bioapplications is provided. First, it highlights the recent achievements of mesoporous silica nanoparticles in biomedical applications, including therapeutic agent delivery, multimodal imaging and theranostics, and bone tissue engineering and repair. Second, the research in evaporation‐induced self‐assembly (EISA)‐based mesostructured silica thin films and cell‐directed EISA in bio/nano interfaces for various bioapplications, such as bioactive coatings, biosensing, and living cell immobilization, has been reviewed. Third, the pioneering work in biomimetic silicification/immobilization of biomolecules and bio‐organisms and silica bioreplication of complex bio‐organisms is summarized. Finally, it is concluded with personal perspectives on the directions of future work on this field.

Lei, Qi↗
DOE OSTI2019

SupraCells: Living Mammalian Cells Protected within Functional Modular Nanoparticle‐Based Exoskeletons

Abstract Creating a synthetic exoskeleton from abiotic materials to protect delicate mammalian cells and impart them with new functionalities could revolutionize fields like cell‐based sensing and create diverse new cellular phenotypes. Herein, the concept of “SupraCells,” which are living mammalian cells encapsulated and protected within functional modular nanoparticle‐based exoskeletons, is introduced. Exoskeletons are generated within seconds through immediate interparticle and cell/particle complexation that abolishes the macropinocytotic and endocytotic nanoparticle internalization pathways that occur without complexation. SupraCell formation is shown to be generalizable to wide classes of nanoparticles and various types of cells. It induces a spore‐like state, wherein cells do not replicate or spread on surfaces but are endowed with extremophile properties, for example, resistance to osmotic stress, reactive oxygen species, pH, and UV exposure, along with abiotic properties like magnetism, conductivity, and multifluorescence. Upon decomplexation cells return to their normal replicative states. SupraCells represent a new class of living hybrid materials with a broad range of functionalities.

Zhu, Wei↗
DOE OSTI2018

Lipid-Coated Mesoporous Silica Nanoparticles for the Delivery of the ML336 Antiviral to Inhibit Encephalitic Alphavirus Infection

Abstract Venezuelan equine encephalitis virus (VEEV) poses a major public health risk due to its amenability for use as a bioterrorism agent and its severe health consequences in humans. ML336 is a recently developed chemical inhibitor of VEEV, shown to effectively reduce VEEV infection in vitro and in vivo . However, its limited solubility and stability could hinder its clinical translation. To overcome these limitations, lipid-coated mesoporous silica nanoparticles (LC-MSNs) were employed. The large surface area of the MSN core promotes hydrophobic drug loading while the liposome coating retains the drug and enables enhanced circulation time and biocompatibility, providing an ideal ML336 delivery platform. LC-MSNs loaded 20 ± 3.4 μg ML336/mg LC-MSN and released 6.6 ± 1.3 μg/mg ML336 over 24 hours. ML336-loaded LC-MSNs significantly inhibited VEEV in vitro in a dose-dependent manner as compared to unloaded LC-MSNs controls. Moreover, cell-based studies suggested that additional release of ML336 occurs after endocytosis. In vivo safety studies were conducted in mice, and LC-MSNs were not toxic when dosed at 0.11 g LC-MSNs/kg/day for four days. ML336-loaded LC-MSNs showed significant reduction of brain viral titer in VEEV infected mice compared to PBS controls. Overall, these results highlight the utility of LC-MSNs as drug delivery vehicles to treat VEEV.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Engineering of large-pore lipid-coated mesoporous silica nanoparticles for dual cargo delivery to cancer cells

Lipid-coated mesoporous silica nanoparticles (LC-MSNs) have recently emerged as a next-generation cargo delivery nanosystem combining the unique attributes of both the organic and inorganic components. The high surface area biodegradable inorganic mesoporous silica core can accommodate multiple classes of bio-relevant cargos in large amounts, while the supported lipid bilayer coating retains the cargo and increases the stability of the nanocarrier in bio-relevant media which should promote greater bio-accumulation of LC-MSNs in cancer sites. In this paper, we report on the optimization of various sol–gel synthesis (pH, stirring speed) and post-synthesis (hydrothermal treatment) procedures to enlarge the MSN pore size and tune the surface chemistry so as to enable loading and delivery of large biomolecules. Finally, the proof of concept of the dual cargo-loaded nanocarrier has been demonstrated in immortalized cervical cancer HeLa cells using MSNs of various fine-tuned pore sizes.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Pendant/bridged/mesoporous silsesquioxane nanoparticles: Versatile and biocompatible platforms for smart delivery of therapeutics

Silsesquioxane nanoparticles are composed of repetitive organosilica fragments in their frameworks and are now recognized to have outstanding functional fertility. Depending on the organosilane and the synthetic pathways, silsesquioxane NPs can be pendant, bridged, dense or porous. Recently the diverse functionalities of mesoporous silsesquioxane nanoparticles have been exploited for the sake of drug-related biomedicine. Fine-tuning the silsesquioxane nanoparticles characteristics allow not only a superior retention capacity of therapeutics without the need of any further modification, but also a controlled release through various environmentally-stimulated triggers. Furthermore, the main focus of the present review is to highlight the different types of silsesquioxane nanoparticles and their exceptional features focused on controlled delivery of drugs, proteins, antibodies and DNA through pH, redox or light stimuli.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Multifunctional Protocells for Enhanced Penetration in 3D Extracellular Tumoral Matrices

The high density of the extracellular matrix in solid tumors is an important obstacle to nanocarriers for reaching deep tumor regions and has severely limited the efficacy of administrated nanotherapeutics. The use of proteolytic enzymes prior to nanoparticle administration or directly attached to the nanocarrier surface has been proposed to enhance their penetration, but the low in vivo stability of these macromolecules compromises their efficacy and strongly limits their application. Herein, we have designed a multifunctional nanocarrier able to transport cytotoxic drugs to deep areas of solid tumors and once there, to be engulfed by tumoral cells causing their destruction. This system is based on mesoporous silica nanocarriers encapsulated within supported lipid bilayers (SLBs). The SLB avoids premature release of the housed drug while providing high colloidal stability and an easy to functionalize surface. The tumor penetration property is provided by attachment of engineered polymeric nanocapsules that transport and controllably unveil and release the proteolytic enzymes that in turn digest the extracellular matrix, facilitating the nanocarrier diffusion through the matrix. Additionally, targeting properties were endowed by conjugating an antibody specific to the investigated tumoral cells to enhance binding, internalization, and drug delivery. This multifunctional design improves the therapeutic efficacy of the transported drug as a consequence of its more homogeneous distribution throughout the tumoral tissue.

60 APPLIED LIFE SCIENCES↗