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  1. Schematic representation of preferential uptake of good's buffer-coated PLGA nanoparticles into human breast cancer cells. Created with biorender.com.

     
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    Free, publicly-accessible full text available December 4, 2024
  2. Latent bloodstains can be visualized using a selective turn-on NIR fluorescence dye responsive to serum albumin. This non-destructive method can detect aged bloodstains and image latent blood fingerprint patterns against colorful backgrounds.

     
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    Free, publicly-accessible full text available September 8, 2024
  3. Free, publicly-accessible full text available October 31, 2024
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  5. Linear-dendritic block copolymers (LDBCs) have emerged as promising materials for drug delivery applications, with their hybrid structure exploiting advantageous properties of both linear and dendritic polymers. LDBCs have promising encapsulation efficiencies that can be used to encapsulate both hydrophobic and hydrophilic dyes for bioimaging, cancer therapeutics, and small biomolecules. Additionally, LDBCS can be readily functionalized with varying terminal groups for more efficient targeted delivery. However, depending on structural composition and surface properties, LDBCs also exhibit high dispersities ( Đ ), poor shelf-life, and potentially high cytotoxicity to non-target interfacing blood cells during intravenous drug delivery. Here, we show that choline carboxylic acid-based ionic liquids (ILs) electrostatically solvate LDBCs by direct dissolution and form stable and biocompatible IL-integrated LDBC nano-assemblies. These nano-assemblies are endowed with red blood cell-hitchhiking capabilities and show altered cellular uptake behavior ex vivo . When modified with choline and trans -2-hexenoic acid, IL-LDBC dispersity dropped by half compared to bare LDBCs, and showed a significant shift of the cationic surface charge towards neutrality. Proton nuclear magnetic resonance spectroscopy evidenced twice the total amount of IL on the LDBCs relative to an established IL-linear PLGA platform. Transmission electron microscopy suggested the formation of a nanoparticle surface coating, which acted as a protective agent against RBC hemolysis, reducing hemolysis from 73% (LDBC) to 25% (IL-LDBC). However, dramatically different uptake behavior of IL-LDBCs vs. IL-PLGA NPs in RAW 264.7 macrophage cells suggests a different conformational IL-NP surface assembly on the linear versus the linear-dendritic nanoparticles. These results suggest that by controlling the physical chemistry of polymer-IL interactions and assembly on the nanoscale, biological function can be tailored toward the development of more effective and more precisely targeted therapies. 
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  6. Abstract

    Delivering cargo to the central nervous system (CNS) remains a pharmacological challenge. For infectious diseases such as HIV, the CNS acts as a latent reservoir that is inadequately managed by systemic antiretrovirals (ARTs). ARTs thus cannot eradicate HIV, and given CNS infection, patients experience neurological deficits collectively referred to as “neuroHIV”. Herein, the development of bioinspired ionic liquid‐coated nanoparticles (IL‐NPs) for in situ hitchhiking on red blood cells (RBCs) is reported, which enables 48% brain delivery of intracarotid arterial‐ infused cargo. Moreover, IL choline trans‐2‐hexenoate (CA2HA 1:2) demonstrates preferential accumulation in parenchymal microglia over endothelial cells post‐delivery. This study further demonstrates successful loading of abacavir (ABC), an ART that is challenging to encapsulate, into IL‐NPs, and verifies retention of antiviral efficacy in vitro. IL‐NPs are not cytotoxic to primary human peripheral blood mononuclear cells (PBMCs) and the CA2HA 1:2 coating itself confers notable anti‐viremic capacity. In addition, in vitro cell culture assays show markedly increased uptake of IL‐NPs into neural cells compared to bare PLGA nanoparticles. This work debuts bioinspired ionic liquids as promising nanoparticle coatings to assist CNS biodistribution and has the potential to revolutionize the delivery of cargos (i.e., drugs, viral vectors) through compartmental barriers such as the blood‐brain‐barrier (BBB).

     
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  7. Abstract

    Ionic liquids (ILs) have emerged as promising biomaterials for enhancing drug delivery by functionalizing polymeric nanoparticles (NPs). Despite the biocompatibility and biofunctionalization they confer upon the NPs, little is understood regarding the degree in which non‐covalent interactions, particularly hydrogen bonding and electrostatic interactions, govern IL‐NP supramolecular assembly. Herein, we use salt (0‐1 M sodium sulfate) and acid (0.25 M hydrochloric acid at pH 4.8) titrations to disrupt IL‐functionalized nanoassembly for four different polymeric platforms during synthesis. Through quantitative1H‐nuclear magnetic resonance spectroscopy and dynamic light scattering, we demonstrate that the driving force of choline trans‐2‐hexenoate (CA2HA 1:1) IL assembly varies with either hydrogen bonding or electrostatics dominating, depending on the structure of the polymeric platform. In particular, the covalently bound or branched 50:50 block co‐polymer systems (diblock PEG‐PLGA [DPP] and polycaprolactone [PCl]‐poly[amidoamine] amine‐based linear‐dendritic block co‐polymer) are predominantly affected by hydrogen bonding disruption. In contrast, a purely linear block co‐polymer system (carboxylic acid terminated poly[lactic‐co‐glycolic acid]) necessitates both electrostatics and hydrogen bonding to assemble with IL and a two‐component electrostatically bound system (electrostatic PEG‐PLGA [EPP]) favors hydrogen‐bonding with electrostatics serving as a secondary role.

     
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  8. Abstract

    Ionic liquids (ILs) have been shown to be effective transdermal penetrants of pharmaceutically active ingredients, including small molecules and proteins. The presence of water within ionic liquids has been demonstrated to play a critical role in  their structural organization on the molecular level. However, the impact of water on IL transdermal transport efficacy has yet to be investigated. Herein, a water concentration gradient (0%–100% v/v) is tested to evaluate  choline trans‐2‐octenoic (CA2OE)‐mediated transport of a hydrophilic model drug dextran (10000 Da) in an ex vivo porcine skin model.Compared to 2:1, 1:1, 1:4, and 1:5 ionic ratio formulations, 50% v/v CA2OE 1:2‐water evidences the greatest success at transporting dextran to the acceptor fluid. Physicochemical characterization (dynamic light scattering (DLS), scanning electron microscopy (SEM), optical density (O.D.), Fourier transform infrared spectroscopy (FTIR), fluorescent microscopy, and rheology) is conducted to test both bulk and nanoscale‐level CA2OE 1:2–water interactions. It is hypothesized that the presence of microemulsions in the CA2OE 1:2 75% v/v formulation accounted for the severely decreased transport compared to the 50%. It is thus critical to comprehensively consider interactions between IL components, co‐solvents, anddrug molecules when formulating ILs for transdermal transport applications.

     
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  9. Abstract

    Macrophages play a diverse, key role in many pathologies, including inflammatory diseases, cardiovascular diseases, and cancer. However, many therapeutic strategies targeting macrophages suffer from systemic off‐target toxicity resulting in notoriously narrow therapeutic windows. To address this shortcoming, the development of poly(propylene sulfide)‐b‐poly(methacrylamidoglucopyranose) [PPS‐b‐PMAG] diblock copolymer‐based nanoparticles (PMAG NPs) capable of targeting macrophages and releasing drug in the presence of reactive oxygen species (ROS) is reported. PMAG NPs have desirable physicochemical properties for systemic drug delivery, including slightly negative surface charge, ≈100 nm diameter, and hemo‐compatibility. Additionally, due to the presence of PPS in the NP core, PMAG NPs release drug cargo preferentially in the presence of ROS. Importantly, PMAG NPs display high cytocompatibility and are taken up by macrophages in cell culture at a rate ≈18‐fold higher than PEGMA NPs—NPs composed of PPS‐b‐poly(oligoethylene glycol methacrylate). Computational studies indicate that PMAG NPs likely bind with glucose transporters such as GLUT 1/3 on the macrophage cell surface to facilitate high levels of internalization. Collectively, this study introduces glycopolymeric NPs that are uniquely capable of both receptor‐ligand targeting to macrophages and ROS‐dependent drug release and that can be useful in many immunotherapeutic settings.

     
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