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Missouri University of Science and Technology

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Articles 1 - 30 of 288

Full-Text Articles in Biomedical Engineering and Bioengineering

Upar-Guided Dendrimer Gel Nanoparticles Reprogram Inflammation To Stabilize Atherosclerotic Plaques, Hsin Yin Chuang, Huari Kou, Yue-Wern Huang, Hu Yang Jul 2026

Upar-Guided Dendrimer Gel Nanoparticles Reprogram Inflammation To Stabilize Atherosclerotic Plaques, Hsin Yin Chuang, Huari Kou, Yue-Wern Huang, Hu Yang

Biological Sciences Faculty Research & Creative Works

Atherosclerosis is characterized by lipid deposition, chronic inflammation, and apoptosis within the arterial wall, leading to plaque progression and instability. Current lipid-lowering therapies fail to fully address residual cardiovascular risk driven by local inflammation and cell death. Here, we report the development of uPA-functionalized, rapamycin-encapsulated dendrimer nanoparticles (G5PM-uPA/RA) that preferentially accumulate in urokinase plasminogen activator receptor (uPAR)-enriched atherosclerotic plaque, including macrophage- and apoptosis-rich lesion microenvironments. G5PM-uPA/RA was constructed by cross-linking reaction-enabled flash nanoprecipitation in a custom-made multi-inlet vortex mixer, followed by thiol-maleimide conjugation of uPA for uPAR-guided targeting. The nanoparticles demonstrated uniform morphology, favorable stability, and efficient rapamycin loading. In …


Oriented Electrospun Fibers Of Poly(Pro-Curcumin/Peg) Sequester Reactive Oxygen Species And Promote The Growth Of Schwann Cells, Jack W. Devlin, Payton R. O'Connor, Conrad H. Cheung, John T. Leman, Martin Oudega, Edmund F. Palermo, Ryan J. Gilbert Jun 2026

Oriented Electrospun Fibers Of Poly(Pro-Curcumin/Peg) Sequester Reactive Oxygen Species And Promote The Growth Of Schwann Cells, Jack W. Devlin, Payton R. O'Connor, Conrad H. Cheung, John T. Leman, Martin Oudega, Edmund F. Palermo, Ryan J. Gilbert

Chemical and Biochemical Engineering Faculty Research & Creative Works

In the biological injury microenvironment, pathologically elevated oxidative stress hinders healthy cell migration. Aligned electrospun fibers are used as tissue engineering scaffolds to support and guide the directionality of cell migration. The ability of cells in the central nervous system to sequester and quench reactive oxygen species is limited, and most electrospun fibers do not exert any antioxidant activity on contact. Thus, the challenge remains in designing a scaffold that can both guide cells to the injury site as well as sequester and quench excess free radicals, allowing cells to thrive and potentially regenerate. Curcumin is a well-known, potent antioxidant, …


Emerging Biomaterials For Next-Generation Wound Healing: From Infection Control To Tissue Regeneration, Unqa Mustafa, Aiman Kaleem, Syeda Zunaira Bukhari, Hamna Riaz, Maryam Iftikhar, Muhammad Usman Munir, Xianghao Xiao, Mingwu Shen, Xiangyang Shi, Mostafa Yazdi, Ayesha Ihsan Jun 2026

Emerging Biomaterials For Next-Generation Wound Healing: From Infection Control To Tissue Regeneration, Unqa Mustafa, Aiman Kaleem, Syeda Zunaira Bukhari, Hamna Riaz, Maryam Iftikhar, Muhammad Usman Munir, Xianghao Xiao, Mingwu Shen, Xiangyang Shi, Mostafa Yazdi, Ayesha Ihsan

Chemical and Biochemical Engineering Faculty Research & Creative Works

Wound healing is a multifactorial biological process that regenerates damaged tissues through a series of molecular and cellular events in a coordinated manner. An interruption in this cascade can lead to impaired healing, especially in diabetic complications, where effective treatment is crucial for controlling infections and promoting tissue regeneration. Recent advances in bioengineering and digital health have catalyzed the development of next-generation wound therapies capable of actively modulating the wound microenvironment, promoting regeneration, and enabling real-time clinical assessment. This review summarizes the fundamentals of physiological wound healing and highlights the significant developments in biomaterial dressings and scaffolds, 3D bioprinting, as …


Uptake And Fate Of Silver And Zinc Engineered Nanoparticles In Maize Under Single And Binary Dosing Soil Ecosystems, Lei Xu, Qingbo Yang, Xingmao Ma, Honglan Shi, John Yang, Hu Yang, Samira Mahdi, Ying Wang, Young Shin Jun Apr 2026

Uptake And Fate Of Silver And Zinc Engineered Nanoparticles In Maize Under Single And Binary Dosing Soil Ecosystems, Lei Xu, Qingbo Yang, Xingmao Ma, Honglan Shi, John Yang, Hu Yang, Samira Mahdi, Ying Wang, Young Shin Jun

Chemistry Faculty Research & Creative Works

Recent agricultural applications of engineered metallic nanoparticles (ENPs) have raised concerns about their uptake and fate in plants. To understand this critical issue, this study investigated the fate and uptake of silver (Ag) and zinc oxide (ZnO) ENPs in maize (Zea mays L.) after single or binary ENP exposure in soil. Results indicated that both Zn and Ag elemental concentrations in roots increased with increasing ENP dosage. Ag NPs in the tissues were detected, but not Zn NPs. Ag NP concentration was 3 times higher in the roots than in the shoots at low Ag NP dosing, while Ag NP …


The Stability Study Of Dna-Polymer Hybrids For Nanotechnology Applications, Ethan Kuehn, Milan Jebaraj Apr 2026

The Stability Study Of Dna-Polymer Hybrids For Nanotechnology Applications, Ethan Kuehn, Milan Jebaraj

Miners Solving for Tomorrow Research Conference

DNA nanostructures have garnered increasing interest in their application as drug delivery vehicles. However, DNA is susceptible to degradation under physiological conditions. To remedy this, we have devised a novel method to coat DNA nanostructures with the polysaccharide chitosan (a natural derivative of chitin). Chitosan binds to DNA electrostatically and inhibits nuclease activity that would normally degrade DNA in a physiological environment. We used both agarose gel electrophoresis (AGE) and atomic force microscopy (AFM) to determine the stability of DNA before and after immersion in a simulated biological environment. Physiological conditions were mimicked by incubating the DNA in cell culture …


Dendrimer Nanogels With Built-In Free Radical Scavenging Enable Efficient Topical Delivery Of A Hydrophilic Antioxidant To Restore Lens Redox Balance For Cataract Treatment, Lin Qi, Huari Kou, Anna Chernatynskaya, Da Huang, Vimalin Jeyalatha Mani, Humeyra Karacal, Nuran Ercal, Hu Yang Apr 2026

Dendrimer Nanogels With Built-In Free Radical Scavenging Enable Efficient Topical Delivery Of A Hydrophilic Antioxidant To Restore Lens Redox Balance For Cataract Treatment, Lin Qi, Huari Kou, Anna Chernatynskaya, Da Huang, Vimalin Jeyalatha Mani, Humeyra Karacal, Nuran Ercal, Hu Yang

Chemistry Faculty Research & Creative Works

Cataract is a leading cause of vision impairment worldwide and are primarily caused by oxidative stress that damages and aggregates lens proteins, leading to lens opacification. However, the eye's anatomical barriers limit the penetration and bioavailability of antioxidant therapies. To address this challenge, a dendrimer-based nanogel with a built-in reactive oxygen species (ROS)-scavenging capability developed by us was employed to deliver the antioxidant N-acetylcysteine (NAC) to the lens. NAC was loaded into a generation-5 PEGylated poly(amidoamine) dendrimer (G5-PEG-TK, termed the GPT) nanogel. The resulting NAC-GPT was characterized for its ROS-scavenging activity, bioavailability, and corneal permeability. The efficacy of NAC-GPT was …


Ionic Liquid Pilocarpine Serves As Therapeutic Cosolvent And Permeation Enhancer For Glaucoma Medication, Ashish Trital, Lei Xu, Burhan Ates, Tzu Chen Wang, Vimalin Mani, Hu Yang Mar 2026

Ionic Liquid Pilocarpine Serves As Therapeutic Cosolvent And Permeation Enhancer For Glaucoma Medication, Ashish Trital, Lei Xu, Burhan Ates, Tzu Chen Wang, Vimalin Mani, Hu Yang

Chemical and Biochemical Engineering Faculty Research & Creative Works

The efficacy of hydrophobic ocular drugs is significantly hindered by their low bioavailability, for which poor water solubility is a major contributing factor. In this work, we synthesized pilocarpine-derived ionic liquid [Pilo-OEG] Cl (PO) and evaluated its cosolvent properties for the codelivery of the hydrophobic antiglaucoma drug brimonidine (BM) for glaucoma therapy. Pilocarpine was quaternized with 2-[2-(2-chloroethoxy) ethoxy] ethanol in a one-pot reaction to yield PO, and its structure was confirmed using 1H NMR and FT-IR spectroscopy methods and further characterized for its rheological property and thermal stability. The HET-CAM assay and cell viability study showed that PO was …


Neuproio: A Dual-Action Solid Drug Nanoparticle Topical Formulation For Simultaneous Intraocular Pressure Reduction And Neuroprotection For Glaucoma, Lei Xu, Mu Li, Lin Qi, Tzu Chen Wang, Dong Liu, Vimalin Jeyalatha Mani, Hsin Yin Chuang, Qingbo Yang, Ruipu Mu, Samira Mahdi, Da Huang, Honglan Shi, Yang Hu, Hu Yang Feb 2026

Neuproio: A Dual-Action Solid Drug Nanoparticle Topical Formulation For Simultaneous Intraocular Pressure Reduction And Neuroprotection For Glaucoma, Lei Xu, Mu Li, Lin Qi, Tzu Chen Wang, Dong Liu, Vimalin Jeyalatha Mani, Hsin Yin Chuang, Qingbo Yang, Ruipu Mu, Samira Mahdi, Da Huang, Honglan Shi, Yang Hu, Hu Yang

Chemical and Biochemical Engineering Faculty Research & Creative Works

Glaucoma is a leading cause of irreversible blindness, primarily due to elevated intraocular pressure (IOP) that damages the retina and optic nerve. Most topical glaucoma treatments focus solely on IOP-lowering without direct neuroprotection, as drug delivery to the posterior eye is challenging. Here, we developed NeuProIO, a dual-action solid drug nanoparticle (NP) eye drop for simultaneous IOP reduction and neuroprotection. Using flash nanoprecipitation in a multi-inlet vortex mixer, we fabricated the first NeuProIO solid drug NPs incorporating the repurposed neuroprotective agent maprotiline (MAP) and the IOP-lowering agent betaxolol (BX), forming MAP/BX NPs for synergistic glaucoma treatment. The NeuProIO improved stability …


Orchestrating Bone Healing: Biomaterial-Driven Immunoengineering Of The Bone Microenvironment For Advanced Regenerative Therapies, Ah Joung Rachel Yu, Mohammad Reza Zare, Edikan Ogunnaike, Mostafa Yazdi Jan 2026

Orchestrating Bone Healing: Biomaterial-Driven Immunoengineering Of The Bone Microenvironment For Advanced Regenerative Therapies, Ah Joung Rachel Yu, Mohammad Reza Zare, Edikan Ogunnaike, Mostafa Yazdi

Chemical and Biochemical Engineering Faculty Research & Creative Works

Bone regeneration is a multistage and tightly regulated process driven by coordinated interactions between the immune and skeletal systems. While inflammation is essential for initiating repair, its dysregulation contributes to delayed union, nonunion, and impaired healing commonly seen in trauma, chronic disease, and aging. Traditional interventions, including autografts and inert biomaterials, provide structural support but fail to engage or modulate the immune microenvironment that governs successful regeneration. Emerging research in osteoimmunology has revealed the centrality of immune cell populations such as macrophages, T regulatory cells, dendritic cells, and myeloid-derived suppressor cells in directing osteogenesis, angiogenesis, and the resolution of inflammation. …


Injectable Borate/Borosilicate Bioactive Glass Systems For The Regeneration Of Hard Tissue – A Critical Review Of The Literature, S. Sina Mohammadi, Sunjeev S. Phull, Ryan J. Gilbert, Mark R. Towler Jan 2026

Injectable Borate/Borosilicate Bioactive Glass Systems For The Regeneration Of Hard Tissue – A Critical Review Of The Literature, S. Sina Mohammadi, Sunjeev S. Phull, Ryan J. Gilbert, Mark R. Towler

Chemical and Biochemical Engineering Faculty Research & Creative Works

Bone defects caused by trauma, infection, or tumor resection remain difficult to treat because successful repair requires both structural restoration and control of the local pathological microenvironment. Osteolysis, defined as pathological bone resorption, is central to many of these conditions and is commonly driven by excessive osteoclast activity. Clinically translated injectable products such as NovaBone® Putty demonstrate the value of moldable bioactiveglass grafts for defect filling; however, conventional silicate bioactive glasses are permanent and provide limited therapeutic ion release. This limitation has motivated the development of injectable borate bioactive glass (B-BGs) and injectable borosilicate bioactive glass (BS-BG) systems as more …


Engineered Multifunctional Drug-Loaded Dendrimer Nanoparticles For Glaucoma: Triple Mechanism Via Antioxidant Activity, Iron Chelation, And Enhanced Ocular Transport, Burhan Ates, Ashish Trital, Vimalin Jeyalatha Mani, Lei Xu, Jonathan Kenlee, Nuran Ercal, Hu Yang Dec 2025

Engineered Multifunctional Drug-Loaded Dendrimer Nanoparticles For Glaucoma: Triple Mechanism Via Antioxidant Activity, Iron Chelation, And Enhanced Ocular Transport, Burhan Ates, Ashish Trital, Vimalin Jeyalatha Mani, Lei Xu, Jonathan Kenlee, Nuran Ercal, Hu Yang

Chemistry Faculty Research & Creative Works

In this study, we developed multifunctional nanoparticles based on polyamidoamine (PAMAM) dendrimers functionalized with caffeic acid (CA) and poly (ethylene glycol) maleimide (PEGM) for the topical delivery of hydrophobic antiglaucoma drugs brimonidine (BM) and betaxolol (BX). The PAMAM-CA and PAMAM-CA-PEGM conjugates exhibited antioxidant and iron-chelating activities in a dose-dependent manner. BM- and BX-loaded dendrimer nanoparticles produced using a multi-inlet vortex mixer showed uniform spherical morphology (∼80 nm by TEM) and hydrated sizes of ∼135-144 nm by DLS. Both nano formulations demonstrated high cytocompatibility with human corneal epithelial cells and were nonirritant in the HET-CAM assay, with PEGM further improving cytocompatibility. …


Dendrimer Gel Nanoparticles With Dual-Targeting Of Upar And Ribonucleotide Reductase R2 Influence Necrosis, Apoptosis, And Cell Cycle Arrest In Triple-Negative Breast Cancer, Hsin Yin Chuang, Yue-Wern Huang, Hu Yang Dec 2025

Dendrimer Gel Nanoparticles With Dual-Targeting Of Upar And Ribonucleotide Reductase R2 Influence Necrosis, Apoptosis, And Cell Cycle Arrest In Triple-Negative Breast Cancer, Hsin Yin Chuang, Yue-Wern Huang, Hu Yang

Biological Sciences Faculty Research & Creative Works

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with limited treatment options due to the absence of estrogen (ER), progesterone (PR), and human epidermal growth factor receptor 2 (HER2) receptors. We previously developed highly adaptable polyamidoamine (PAMAM) dendrimer-based gel nanoparticles (GDP-uPA/GTI) with dual-targeting capabilities against urokinase-type plasminogen activator receptor (uPAR) and ribonucleotide reductase R2 (R2) to achieve selective antitumor effects. In this study, we investigated the underlying mechanisms of GDP-uPA/GTI-induced tumor inhibition. In vivo, GDP-uPA/GTI significantly downregulated R2 expression and activated caspase 8 and caspase 3, indicating caspase-dependent apoptosis. Histological evaluation of major organs revealed no observable toxicity. …


Highly Adaptable Dendrimer Gel Nanoparticles With Dual Targeting Of Upar And Ribonucleotide Reductase R2 For Better Retention And Improved Therapeutic Outcomes In Triple-Negative Breast Cancer, Hsin Yin Chuang, Da Huang, Lin Qi, Vidit Singh, Anna Chernatynskaya, Yue-Wern Huang, Hu Yang Jun 2025

Highly Adaptable Dendrimer Gel Nanoparticles With Dual Targeting Of Upar And Ribonucleotide Reductase R2 For Better Retention And Improved Therapeutic Outcomes In Triple-Negative Breast Cancer, Hsin Yin Chuang, Da Huang, Lin Qi, Vidit Singh, Anna Chernatynskaya, Yue-Wern Huang, Hu Yang

Biological Sciences Faculty Research & Creative Works

Triple-negative breast cancer (TNBC) accounts for approximately 15% of breast cancers and lacks estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), rendering it unresponsive to hormonal or anti-HER2 therapies. Due to its poor prognosis and limited treatment options, there is an urgent need for targeted therapies. In this study, we developed highly adaptable polyamidoamine (PAMAM) dendrimer-based gel nanoparticles with dual-targeting capabilities against urokinase-type plasminogen activator receptor (uPAR) and ribonucleotide reductase R2 (R2). These nanoparticles were designed to target both TNBC cells and cancer-associated stromal cells by leveraging uPA-uPAR interactions and delivering the antisense oligonucleotide …


Tumor-Specific Surface Marker–Independent Targeting Of Tumors Through Nanotechnology And Bioorthogonal Glycochemistry, Hyesun Hyun, Bo Sun, Mostafa Yazdimamaghani, Albert Wielgus, Yue Wang, Stephanie Ann Montgomery, Tian Zhang, Jianjun Cheng, Jonathan S. Serody, Andrew Z. Wang May 2025

Tumor-Specific Surface Marker–Independent Targeting Of Tumors Through Nanotechnology And Bioorthogonal Glycochemistry, Hyesun Hyun, Bo Sun, Mostafa Yazdimamaghani, Albert Wielgus, Yue Wang, Stephanie Ann Montgomery, Tian Zhang, Jianjun Cheng, Jonathan S. Serody, Andrew Z. Wang

Chemical and Biochemical Engineering Faculty Research & Creative Works

Biological targeting is crucial for effective cancer treatment with reduced toxicity but is limited by the availability of tumor surface markers. To overcome this, we developed a nanoparticle-based (NP-based), tumor-specific surface marker–independent (TRACER) targeting approach. Utilizing the unique biodistribution properties of NPs, we encapsulated Ac4ManNAz (Maz) to selectively label tumors with azide-reactive groups. Surprisingly, while NP-delivered Maz was cleared by the liver, it did not label macrophages, potentially reducing off-target effects. To exploit this tumor-specific labeling, we functionalized anti–4-1BB Abs with dibenzo cyclooctyne to target azide-labeled tumor cells and activate the immune response. In syngeneic B16F10 melanoma and orthotopic 4T1 …


Modular Molecular Design Of Polymerized Pro-Estrogen Materials Enables Controlled Astrocyte Response, Devan L. Puhl, Alexis Ziemba, Samuel A.T. Ellman, Alex Hsu, Jayant Saksena, Penelope Phillips Falcone, Bailey Balouch, Deniz Rende, Tanner Fink, R. Helen Zha, Ryan J. Gilbert, Edmund F. Palermo Apr 2025

Modular Molecular Design Of Polymerized Pro-Estrogen Materials Enables Controlled Astrocyte Response, Devan L. Puhl, Alexis Ziemba, Samuel A.T. Ellman, Alex Hsu, Jayant Saksena, Penelope Phillips Falcone, Bailey Balouch, Deniz Rende, Tanner Fink, R. Helen Zha, Ryan J. Gilbert, Edmund F. Palermo

Chemical and Biochemical Engineering Faculty Research & Creative Works

The hormone 17β-estradiol (estrogen or "E2") has demonstrated robust neuroprotective properties in countering oxidative stress-induced neurotoxicity, as well as strong neurotrophic properties to promote axonal growth, following injury to the central nervous system (CNS). However, oral or injected E2 is a suboptimal drug, as systemic administration fails to achieve a therapeutic dose at the injury site, in addition to being contraindicated in most male patients. Polymerized pro-drug biomaterials can mitigate these issues by locally releasing small quantities of drug over vastly extended timescales. We sought to study the effect of the biomaterial properties of poly(pro-E2) on astrocyte-surface interactions because astrocytes …


Engineering Pamam Dendrimers For Optimized Drug Delivery, Amin Aleebrahim Dehkordi, Shirin Mollazadeh, Amirreza Talaie, Mostafa Yazdimamaghani Mar 2025

Engineering Pamam Dendrimers For Optimized Drug Delivery, Amin Aleebrahim Dehkordi, Shirin Mollazadeh, Amirreza Talaie, Mostafa Yazdimamaghani

Chemical and Biochemical Engineering Faculty Research & Creative Works

Dendrimers, first introduced by Fritz Vögtle in 1978, have emerged as promising nanocarriers for drug delivery due to their unique branched architecture, large internal cavities, and numerous surface amine groups. These dendrimers efficiently load various drugs through electrostatic interactions, covalent bonding, or encapsulation, owing to their high density of terminal amine groups. However, the inherent cationic nature of PAMAM dendrimers can lead to cytotoxicity and limited systemic circulation due to interactions with negatively charged biomolecules. To address these limitations, surface modification strategies have been developed to enhance targeting, trigger-controlled drug release, and decrease cytotoxicity. This review critically examines recent advancements …


Enhanced Cholesterol Efflux And Atherosclerosis Regression Via Ceh Gene Delivery Using Galactose-Functionalized Dendrimeric Nanoparticles, Huari Kou, Jing Wang, Paul J. Yannie, Da Huang, William J. Korzun, Genta Kakiyama, Siddhartha S. Ghosh, Hu Yang Jan 2025

Enhanced Cholesterol Efflux And Atherosclerosis Regression Via Ceh Gene Delivery Using Galactose-Functionalized Dendrimeric Nanoparticles, Huari Kou, Jing Wang, Paul J. Yannie, Da Huang, William J. Korzun, Genta Kakiyama, Siddhartha S. Ghosh, Hu Yang

Chemical and Biochemical Engineering Faculty Research & Creative Works

Cholesteryl ester hydrolase (CEH) is a critical enzyme in cholesterol ester hydrolysis, influencing cholesterol metabolism and efflux. This study demonstrates that CEH overexpression promotes free cholesterol efflux from macrophages, thereby reducing the lipid burden in existing atherosclerotic plaques. To enable targeted delivery, galactose-functionalized polyamidoamine (PAMAM) dendrimeric nanoparticles were utilized as nanocarriers for hepatic delivery of the CEH expression vector. The therapeutic potential of CEH plasmid-loaded dendrimeric nanoparticles was evaluated in Ldlr-/- mice. Results showed a significant reduction in total lesion area (21%) and aortic arch lesion area (23%) compared to baseline. Lesion component analysis revealed marked decreases in total cholesterol …


Synthesis And Characterization Of Free Radical Scavenging Dendrimer Nanogels Via Cross-Linking Reaction-Enabled Flash Nanoprecipitation, Lin Qi, Da Huang, Huari Kou, Anna Chernatynskaya, Nuran Ercal, Hu Yang Jan 2025

Synthesis And Characterization Of Free Radical Scavenging Dendrimer Nanogels Via Cross-Linking Reaction-Enabled Flash Nanoprecipitation, Lin Qi, Da Huang, Huari Kou, Anna Chernatynskaya, Nuran Ercal, Hu Yang

Chemistry Faculty Research & Creative Works

This work reports the development and evaluation of dendrimer-based nanogels based on Poly amidoamine (PAMAM) dendrimer generation 5, engineered to act as a carrier with reactive oxygen species (ROS)-scavenging capabilities. We developed a cross-linking reaction-enabled flash nanoprecipitation method in which the cross-linking reaction occurs during the flash nanoprecipitation process to form a cross-linked nanostructure. Using this approach, an N-hydroxy succinimide (NHS)-functionalized ROS-responsive thioketal cross-linker (TK-NHS) was synthesized and utilized to cross-link DAB-core PAMAM dendrimer G5, resulting in the formation of G5-TK nanogels. The resulting nanogels were characterized using dynamic light scattering and transmission electron microscopy, and their cytocompatibility, irritancy, cellular …


Scalable Fabrication Of High-Payload Dendrimer-Based Nanoparticles For Targeted Atherosclerosis Therapy, Huari Kou, Lin Qi, Da Huang, Jiandong Wu, Honglan Shi, Hu Yang Jan 2025

Scalable Fabrication Of High-Payload Dendrimer-Based Nanoparticles For Targeted Atherosclerosis Therapy, Huari Kou, Lin Qi, Da Huang, Jiandong Wu, Honglan Shi, Hu Yang

Chemistry Faculty Research & Creative Works

Nanoparticle-based therapeutics hold promise for the treatment of atherosclerosis, but challenges such as low drug-loading capacity and a lack of scalable, controllable production hinder their clinical translation. Flash nanoprecipitation, a continuous synthesis method, offers a potential solution for scalable and reproducible nanoparticle production. In this study, we employed a custom-designed multi-inlet vortex mixer to perform cross-linking reaction-enabled flash nanoprecipitation, facilitating controlled and scalable synthesis of cross-linked Poly amidoamine (PAMAM) dendrimer nanoparticles. Notably, this approach allows simultaneous nanoparticle cross-linking and drug loading in a single step. The mannose moiety enabled specific targeting of macrophages via mannose receptors, enhancing the localization of …


Tumor Microenvironment Immunomodulation By Nanoformulated Tlr 7/8 Agonist And Pi3k Delta Inhibitor Enhances Therapeutic Benefits Of Radiotherapy, Mostafa Yazdimamaghani, Oleg V. Kolupaev, Chaemin Lim, Duhyeong Hwang, Sonia J. Laurie, Charles M. Perou, Alexander V. Kabanov, Jonathan S. Serody Jan 2025

Tumor Microenvironment Immunomodulation By Nanoformulated Tlr 7/8 Agonist And Pi3k Delta Inhibitor Enhances Therapeutic Benefits Of Radiotherapy, Mostafa Yazdimamaghani, Oleg V. Kolupaev, Chaemin Lim, Duhyeong Hwang, Sonia J. Laurie, Charles M. Perou, Alexander V. Kabanov, Jonathan S. Serody

Chemical and Biochemical Engineering Faculty Research & Creative Works

Infiltration of immunosuppressive cells into the breast tumor microenvironment (TME) is associated with suppressed effector T cell (Teff) responses, accelerated tumor growth, and poor clinical outcomes. Previous studies from our group and others identified infiltration of immunosuppressive myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) as critical contributors to immune dysfunction in the orthotopic claudin-low tumor model, limiting the efficacy of adoptive cellular therapy. However, approaches to target these cells in the TME are currently lacking. To overcome this barrier, polymeric micellular nanoparticles (PMNPs) were used for the co-delivery of small molecule drugs activating Toll-like receptors 7 and 8 …


Optimized Fabrication Of Dendritic Mesoporous Silica Nanoparticles As Efficient Delivery System For Cancer Immunotherapy, Varsha Godakhindi, Mostafa Yazdimamaghani, Sudip Kumar Dam, Farzana Ferdous, Andrew Z. Wang, Mubin Tarannum, Jonathan Serody, Juan L. Vivero-Escoto Dec 2024

Optimized Fabrication Of Dendritic Mesoporous Silica Nanoparticles As Efficient Delivery System For Cancer Immunotherapy, Varsha Godakhindi, Mostafa Yazdimamaghani, Sudip Kumar Dam, Farzana Ferdous, Andrew Z. Wang, Mubin Tarannum, Jonathan Serody, Juan L. Vivero-Escoto

Chemical and Biochemical Engineering Faculty Research & Creative Works

In the past decade, cancer immunotherapy has revolutionized the field of oncology. Major immunotherapy approaches such as immune checkpoint inhibitors, cancer vaccines, adoptive cell therapy, cytokines, and immunomodulators have shown great promise in preclinical and clinical settings. Among them, immunomodulatory agents including cancer vaccines are particularly appealing; however, they face limitations, notably the absence of efficient and precise targeted delivery of immune-modulatory agents to specific immune cells and the potential for off-target toxicity. Nanomaterials can play a pivotal role in addressing targeting and other challenges in cancer immunotherapy. Dendritic mesoporous silica nanoparticles (DMSNs) can enhance the efficacy of cancer vaccines …


Type Ii Innate Lymphoid Cell Plasticity Contributes To Impaired Reconstitution After Allogeneic Hematopoietic Stem Cell Transplantation, Sonia J. Laurie, Joseph P. Foster, Danny W. Bruce, Hemamalini Bommiasamy, Oleg V. Kolupaev, Mostafa Yazdimamaghani, Samantha G. Pattenden, Nelson J. Chao, Stefanie Sarantopoulos, Joel S. Parker, Ian J. Davis, Jonathan S. Serody Dec 2024

Type Ii Innate Lymphoid Cell Plasticity Contributes To Impaired Reconstitution After Allogeneic Hematopoietic Stem Cell Transplantation, Sonia J. Laurie, Joseph P. Foster, Danny W. Bruce, Hemamalini Bommiasamy, Oleg V. Kolupaev, Mostafa Yazdimamaghani, Samantha G. Pattenden, Nelson J. Chao, Stefanie Sarantopoulos, Joel S. Parker, Ian J. Davis, Jonathan S. Serody

Chemical and Biochemical Engineering Faculty Research & Creative Works

Type II innate lymphoid cells (ILC2s) maintain homeostasis and barrier integrity in mucosal tissues. In both mice and humans, ILC2s poorly reconstitute after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Determining the mechanisms involved in their impaired reconstitution could improve transplant outcomes. By integrating single-cell chromatin and transcriptomic analyses of transplanted ILC2s, we identify a previously unreported population of converted ILC1-like cells in the mouse small intestine post-transplant. Exposure of ILC2s to proinflammatory cytokines resulted in a mixed ILC1-ILC2 phenotype but was able to convert only a small population of ILC2s to ILC1s, which were found post-transplant. Whereas ILC2s protected against …


Delivery Of Tgfβ3 From Magnetically Responsive Coaxial Fibers Reduces Spinal Cord Astrocyte Reactivity In Vitro, Jessica L. Funnell, Jasper Fougere, Diana Zahn, Silvio Dutz, Ryan J. Gilbert Oct 2024

Delivery Of Tgfβ3 From Magnetically Responsive Coaxial Fibers Reduces Spinal Cord Astrocyte Reactivity In Vitro, Jessica L. Funnell, Jasper Fougere, Diana Zahn, Silvio Dutz, Ryan J. Gilbert

Chemical and Biochemical Engineering Faculty Research & Creative Works

A spinal cord injury (SCI) compresses the spinal cord, killing neurons and glia at the injury site and resulting in prolonged inflammation and scarring that prevents regeneration. Astrocytes, the main glia in the spinal cord, become reactive following SCI and contribute to adverse outcomes. The anti-inflammatory cytokine transforming growth factor beta 3 (TGFβ3) has been shown to mitigate astrocyte reactivity; however, the effects of prolonged TGFβ3 exposure on reactive astrocyte phenotype have not yet been explored. This study investigates whether magnetic core-shell electro spun fibers can be used to alter the release rate of TGFβ3 using externally applied magnetic fields, …


In Vitro Assessment Of Protamine Toxicity With Neural Cells, Its Therapeutic Potential To Counter Chondroitin Sulfate Mediated Neuron Inhibition, And Its Effects On Reactive Astrocytes, Derek W. Nelson, Jessica L. Funnell, Conrad H. Cheung, Geraldine B. Quinones, Christina S. Mendoza, Marvin Bentley, Ryan J. Gilbert Feb 2024

In Vitro Assessment Of Protamine Toxicity With Neural Cells, Its Therapeutic Potential To Counter Chondroitin Sulfate Mediated Neuron Inhibition, And Its Effects On Reactive Astrocytes, Derek W. Nelson, Jessica L. Funnell, Conrad H. Cheung, Geraldine B. Quinones, Christina S. Mendoza, Marvin Bentley, Ryan J. Gilbert

Chemical and Biochemical Engineering Faculty Research & Creative Works

Multiple therapies have been studied to ameliorate the neuroinhibitory cues present after traumatic injury to the central nervous system. Two previous in vitro studies have demonstrated the efficacy of the Food and Drug Administration-approved cardiovascular therapeutic, protamine (PRM), to overcome neuroinhibitory cues presented by chondroitin sulfates; however, the effect of a wide range of PRM concentrations on neuronal and glial cells has not been evaluated. In this study, we investigate the therapeutic efficacy of PRM with primary cortical neurons, hippocampal neurons, mixed glial cultures, and astrocytes. The threshold for PRM toxicity is shown to be at or above 10 µg …


One-Pot Assembly Of Drug-Eluting Silk Coatings With Applications For Nerve Regeneration, Tanner D. Fink, Jessica L. Funnell, Ryan J. Gilbert, R. Helen Zha Jan 2024

One-Pot Assembly Of Drug-Eluting Silk Coatings With Applications For Nerve Regeneration, Tanner D. Fink, Jessica L. Funnell, Ryan J. Gilbert, R. Helen Zha

Chemical and Biochemical Engineering Faculty Research & Creative Works

Clinical use of polymeric scaffolds for tissue engineering often suffers from their inability to promote strong cellular interactions. Functionalization with biomolecules may improve outcomes; however, current functionalization approaches using covalent chemistry or physical adsorption can lead to loss of biomolecule bioactivity. Here, we demonstrate a novel bottom-up approach for enhancing the bioactivity of poly (l-lactic acid) electro spun scaffolds though interfacial coassembly of protein payloads with silk fibroin into nano thin coatings. In our approach, protein payloads are first added into an aqueous solution with Bombyx mori-derived silk fibroin. Phosphate anions are then added to trigger coassembly of the payload …


Pharmacology Of Boldine: Summary Of The Field And Update On Recent Advances, Juan C. Sáez, Justin C. Burrell, Catherine M. Cahill, D. Kacy Cullen, Lakshmi A. Devi, Ryan J. Gilbert, Zachary A. Graham, Vadim J. Gurvich, Leif A. Havton, Ravi Iyengar, Rajesh Khanna, Edmund F. Palermo, Mustafa Siddiq, Carlos A. Toro, Walter Vasquez, Wei Zhao, Christopher P. Cardozo Jan 2024

Pharmacology Of Boldine: Summary Of The Field And Update On Recent Advances, Juan C. Sáez, Justin C. Burrell, Catherine M. Cahill, D. Kacy Cullen, Lakshmi A. Devi, Ryan J. Gilbert, Zachary A. Graham, Vadim J. Gurvich, Leif A. Havton, Ravi Iyengar, Rajesh Khanna, Edmund F. Palermo, Mustafa Siddiq, Carlos A. Toro, Walter Vasquez, Wei Zhao, Christopher P. Cardozo

Chemical and Biochemical Engineering Faculty Research & Creative Works

Over the past decade, boldine, a naturally occurring alkaloid found in several plant species including the Chilean Boldo tree, has garnered attention for its efficacy in rodent models of human disease. Some of the properties that have been attributed to boldine include antioxidant activities, neuroprotective and analgesic actions, hepatoprotective effects, anti-inflammatory actions, cardioprotective effects and anticancer potential. Compelling data now indicates that boldine blocks connexin (Cx) hemichannels (HCs) and that many if not all of its effects in rodent models of injury and disease are due to CxHC blockade. Here we provide an overview of boldine's pharmacological properties, including its …


Method For Continuous Fabrication Of Multi-Functional Nanogels, Hu Yang, Da Huang Jan 2024

Method For Continuous Fabrication Of Multi-Functional Nanogels, Hu Yang, Da Huang

Patents

Nanogels and methods of synthesizing and using these nanogels are provided. The nanogels are formed by mixing a building block (e.g., polymer), crosslinker, preferably a target (e.g., biomedical compound or molecule), and a solvent in a multi-inlet vortex mixer, so as to cause the polymer and crosslinker to react and form a chemically crosslinked polymer network. In embodiments including a target, the target will be interspersed in and among that network and can be physically embedded and/or chemically bound therein.


Fate And Distribution Of Orally-Ingested Ceo2-Nanoparticles Based On A Mouse Model: Implication For Human Health, Xingmao Ma, Xiaoxuan Wang, Lei Xu, Honglan Shi, Hu Yang, Kerstin K. Landrock, Virender K. Sharma, Robert S. Chapkin Jun 2023

Fate And Distribution Of Orally-Ingested Ceo2-Nanoparticles Based On A Mouse Model: Implication For Human Health, Xingmao Ma, Xiaoxuan Wang, Lei Xu, Honglan Shi, Hu Yang, Kerstin K. Landrock, Virender K. Sharma, Robert S. Chapkin

Chemistry Faculty Research & Creative Works

The use of nanoparticles in agrichemical formula and food products as additives has increased their chances of accumulation in humans via oral intake. Due to their potential toxicity, it is critical to understand their fate and distribution following oral intake. Cerium oxide nanoparticle (CeO2NP) is commonly used in agriculture and is highly stable in the environment. as such, it has been used as a model chemical to investigate nanoparticle's distribution and clearance. based on their estimated human exposure levels, 0.15–0.75 mg/kg body weight/day of CeO2NPs with different sizes and surface charges (30–50 nm with negative charge and <25 >nm with positive …


Dendrimer And Dendrimer Gel-Derived Drug Delivery Systems: Breaking Bottlenecks Of Topical Administration Of Glaucoma Medications, Juan Wang, Boxuan Li, Uday B. Kompella, Hu Yang Mar 2023

Dendrimer And Dendrimer Gel-Derived Drug Delivery Systems: Breaking Bottlenecks Of Topical Administration Of Glaucoma Medications, Juan Wang, Boxuan Li, Uday B. Kompella, Hu Yang

Chemical and Biochemical Engineering Faculty Research & Creative Works

Due to high structural flexibility, multidrug carrying capability, and tunable size, dendrimers have been used as suitable carriers for ophthalmic drug delivery. Drug molecules can be either encapsulated or chemically coupled to dendrimers. the nanoscopic size, spheroidal shape, and cationic surface of Poly amidoamine (PAMAM) dendrimers promote their interaction with the cornea and result in prolonged precorneal retention. Dendrimers could be further cross-linked to produce three-dimensional hydrogel networks or dendrimer hydrogels (DH). the properties of the DH can be readily adjusted to maintain both fluidity and adhesiveness, making them suitable for developing topical ocular drug formulations. Micro-/nano- sized DHs, that …


Development Of A Slow-Degrading Polymerized Curcumin Coating For Intracortical Microelectrodes, Alexis M. Ziemba, Mary Clare Crochiere Woodson, Jessica L. Funnell, Douglas Wich, Bailey Balouch, Deniz Rende, Dahlia N. Amato, Jonathan Bao, Ingrid Oprea, Dominica Cao, Neda Bajalo, Evon S. Ereifej, Jeffrey R. Capadona, Edmund F. Palermo, Ryan J. Gilbert Feb 2023

Development Of A Slow-Degrading Polymerized Curcumin Coating For Intracortical Microelectrodes, Alexis M. Ziemba, Mary Clare Crochiere Woodson, Jessica L. Funnell, Douglas Wich, Bailey Balouch, Deniz Rende, Dahlia N. Amato, Jonathan Bao, Ingrid Oprea, Dominica Cao, Neda Bajalo, Evon S. Ereifej, Jeffrey R. Capadona, Edmund F. Palermo, Ryan J. Gilbert

Chemical and Biochemical Engineering Faculty Research & Creative Works

Intracortical microelectrodes are used with brain-computer interfaces to restore lost limb function following nervous system injury. While promising, recording ability of intracortical microelectrodes diminishes over time due, in part, to neuroinflammation. As curcumin has demonstrated neuroprotection through anti-inflammatory activity, we fabricated a 300 nm-thick intracortical microelectrode coating consisting of a polyurethane copolymer of curcumin and polyethylene glycol (PEG), denoted as poly (curcumin-PEG1000 carbamate) (PCPC). The uniform PCPC coating reduced silicon wafer hardness by two orders of magnitude and readily absorbed water within minutes, demonstrating that the coating is soft and hydrophilic in nature. Using an in vitro release model, curcumin …