IU Indianapolis ScholarWorks :: Browsing by Subject "Nanoparticles"

Browsing by Subject "Nanoparticles"

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A TLR7-nanoparticle adjuvant promotes a broad immune response against heterologous strains of influenza and SARS-CoV-2
(Springer Nature, 2023) Yin, Qian; Luo, Wei; Mallajosyula, Vamsee; Bo, Yang; Guo, Jing; Xie, Jinghang; Sun, Meng; Verma, Rohit; Li, Chunfeng; Constantz, Christian M.; Wagar, Lisa E.; Li, Jing; Sola, Elsa; Gupta, Neha; Wang, Chunlin; Kask, Oliver; Chen, Xin; Yuan, Xue; Wu, Nicholas C.; Rao, Jianghong; Chien, Yueh-hsiu; Cheng, Jianjun; Pulendran, Bali; Davis, Mark M.; Microbiology and Immunology, School of Medicine
The ideal vaccine against viruses such as influenza and SARS-CoV-2 must provide a robust, durable and broad immune protection against multiple viral variants. However, antibody responses to current vaccines often lack robust cross-reactivity. Here we describe a polymeric Toll-like receptor 7 agonist nanoparticle (TLR7-NP) adjuvant, which enhances lymph node targeting, and leads to persistent activation of immune cells and broad immune responses. When mixed with alum-adsorbed antigens, this TLR7-NP adjuvant elicits cross-reactive antibodies for both dominant and subdominant epitopes and antigen-specific CD8+ T-cell responses in mice. This TLR7-NP-adjuvanted influenza subunit vaccine successfully protects mice against viral challenge of a different strain. This strategy also enhances the antibody response to a SARS-CoV-2 subunit vaccine against multiple viral variants that have emerged. Moreover, this TLR7-NP augments antigen-specific responses in human tonsil organoids. Overall, we describe a nanoparticle adjuvant to improve immune responses to viral antigens, with promising implications for developing broadly protective vaccines.
Au nanoparticle assembly on cnts using flash induced solid-state dewetting
(2015-04-28) Kulkarni, Ameya; Ryu, Jong Eun; Agarwal, Mangilal; Xie, Jian; Cheng, Ruihua
Carbon Nanotubes (CNTs) are used extensively in various applications where substrate are required to be possessing higher surface area, porosity and electrical and thermal conductivity. Such properties can be enhanced to target a particular gas and biochemical for efficient detection when CNT matrix is functionalized with Nanoparticles (NPs). Conventional functionalization involves harsh oxidation repeated washing, filtration and sonication, which induce defects. The defects lead to hindered mobility of carriers, unwanted doping and also fragmentation of the CNTs in some cases. In this document we demonstrate functionalization of CNT with Au nanoparticles on a macro scale under dry and ambient condition using Xenon ash induced solid-state dewetting. A sputtered thin film was transformed into nanoparticles which were confirmed to be in a state of thermodynamic equilibrium. We worked on 3 nm, 6 nm, 9 nm, 15 nm, 30 nm initial thickness of thin films. Xenon ash parameters of energy, number of pulse, duration of pulse, duration of gap between consecutive pulses were optimized to achieve complete dewetting of Au thin films. 3 nm deposition was in the form of irregular nano-islands which were transformed into stable nanoparticles with a single shot of 10 J/cm2 of 2 ms duration. 6 nm and 9 nm deposition was in form of continues film which was also dewetted into stable nanoparticles with a single pulse but with an increased energy density of 20 J/cm2 and 35 J/cm2 respectively. In case of 15 nm and 30 nm deposition the thin film couldn't be dewetted with a maximum energy density of 50 J/cm2, it was observed that 3 and 4 pulses of 2 ms pulse duration and 2 ms gap duration with an energy density of 50 J/cm2 were required to completely dewet the thicker films. However irregularity was induced in the sizes of the NPs due to Ostwald ripening phenomenon which causes smaller particle within a critical difiusion length to combine and form a larger particle during or after dewetting process. For comparison, the Au thin films were also dewetted by a conventional process involving annealing of samples until the thin film was fully transformed into NPs and the size of NPs seized to grow. Scanning electron microscope (SEM) was used to characterize the samples. Thermodynamic stability of the particles was confirmed with statistical analyses of size distribution after every additional pulse.
Bone-Induced Expression of Integrin β3 Enables Targeted Nanotherapy of Breast Cancer Metastases
(American Association for Cancer Research, 2017-11-15) Ross, Michael H.; Esser, Alison K.; Fox, Gregory C.; Schmieder, Anne H.; Yang, Xiaoxia; Hu, Grace; Pan, Dipanjan; Su, Xinming; Xu, Yalin; Novack, Deborah V.; Walsh, Thomas; Colditz, Graham A.; Lukaszewicz, Gabriel H.; Cordell, Elizabeth; Novack, Joshua; Fitzpatrick, James. A.J.; Waning, David L.; Mohammad, Khalid S.; Guise, Theresa A.; Lanza, Gregory M.; Weilbaecher, Katherine N.; Medicine, School of Medicine
Bone metastases occur in approximately 70% of metastatic breast cancer patients, often leading to skeletal injuries. Current treatments are mainly palliative and underscore the unmet clinical need for improved therapies. In this study, we provide preclinical evidence for an antimetastatic therapy based on targeting integrin β3 (β3), which is selectively induced on breast cancer cells in bone by the local bone microenvironment. In a preclinical model of breast cancer, β3 was strongly expressed on bone metastatic cancer cells, but not primary mammary tumors or visceral metastases. In tumor tissue from breast cancer patients, β3 was significantly elevated on bone metastases relative to primary tumors from the same patient (n = 42). Mechanistic investigations revealed that TGFβ signaling through SMAD2/SMAD3 was necessary for breast cancer induction of β3 within the bone. Using a micelle-based nanoparticle therapy that recognizes integrin αvβ3 (αvβ3-MPs of ∼12.5 nm), we demonstrated specific localization to breast cancer bone metastases in mice. Using this system for targeted delivery of the chemotherapeutic docetaxel, we showed that bone tumor burden could be reduced significantly with less bone destruction and less hepatotoxicity compared with equimolar doses of free docetaxel. Furthermore, mice treated with αvβ3-MP-docetaxel exhibited a significant decrease in bone-residing tumor cell proliferation compared with free docetaxel. Taken together, our results offer preclinical proof of concept for a method to enhance delivery of chemotherapeutics to breast cancer cells within the bone by exploiting their selective expression of integrin αvβ3 at that metastatic site.
Clickable modular polysaccharide nanoparticles for selective cell-targeting
(Elsevier, 2020-04-15) Peuler, Kevin; Dimmitt, Nathan; Lin, Chien-Chi; Biomedical Engineering, School of Engineering and Technology
A therapeutic nanocarrier capable of cell targeting has the potential to reduce off-target effects of otherwise effective drugs. Nanoparticle surface modification can be tailored for specific cells, however multistep surface modification can prove slow and difficult for a variety of cell types. Here, we designed drug carrying polysaccharide based nanoparticles with a layered structure for clickable surface modification. The center of nanoparticle was composed of cationic macromer (e.g., poly-L-lysine) and anionic polysaccharide (e.g., heparin). Furthermore, a ‘clickable’ polysaccharide was installed on the surface of the nanoparticles to permit a wide range of bioconjugation via norbornene-tetrazine click chemistry. The utilities of these layered nanoparticles were demonstrated via enhanced protein sequestration, selective cell targeting (via PEGylation or altering polysaccharide coating), as well as loading and release of chemotherapeutic. The drug-loaded nanocarriers proved cytotoxic to J774A.1 monocytes and MOLM-14 leukemia cells.
Development and Evaluation of Transferrin-Stabilized Paclitaxel Nanocrystal Formulation
(Elsevier, 2014-02-28) Lu, Ying; Wang, Zhao-hui; Li, Tonglei; McNally, Helen; Park, Kinam; Sturek, Michael; Department of Cellular & Integrative Physiology, IU School of Medicine
The aim of the present study was to prepare and evaluate a paclitaxel nanocrystal-based formulation stabilized by serum protein transferrin in a non-covalent manner. The pure paclitaxel nanocrystals were first prepared using an antisolvent precipitation method augmented by sonication. The serum protein transferrin was selected for use after evaluating the stabilizing effect of several serum proteins including albumin and immunoglobulin G. The formulation contained approximately 55~60% drug and was stable for at least 3 months at 4 °C. In vivo antitumor efficacy studies using mice inoculated with KB cells demonstrate significantly higher tumor inhibition rate of 45.1% for paclitaxel-transferrin formulation compared to 28.8% for paclitaxel nanosuspension treatment alone. Interestingly, the Taxol® formulation showed higher antitumor activity than the paclitaxel-transferrin formulation, achieving a 93.3% tumor inhibition rate 12 days post initial dosing. However, the paclitaxel-transferrin formulation showed a lower level of toxicity, which is indicated by steady increase in body weight of mice over the treatment period. In comparison, treatment with Taxol® resulted in toxicity issues as body weight decreased. These results suggest the potential benefit of using a serum protein in a non-covalent manner in conjunction with paclitaxel nanocrystals as a promising drug delivery model for anticancer therapy.
Disruption of Aedes aegypti Olfactory System Development through Chitosan/siRNA Nanoparticle Targeting of semaphorin-1a
(Public Library of Science, 2013-05-16) Mysore, Keshava; Flannery, Ellen M.; Tomchaney, Michael; Severson, David W.; Duman-Scheel, Molly; Medical and Molecular Genetics, School of Medicine
Despite the devastating impact of mosquito-borne illnesses on human health, surprisingly little is known about mosquito developmental biology, including development of the olfactory system, a tissue of vector importance. Analysis of mosquito olfactory developmental genetics has been hindered by a lack of means to target specific genes during the development of this sensory system. In this investigation, chitosan/siRNA nanoparticles were used to target semaphorin-1a (sema1a) during olfactory system development in the dengue and yellow fever vector mosquito Aedes aegypti. Immunohistochemical analyses and anterograde tracing of antennal sensory neurons, which were used to track the progression of olfactory development in this species, revealed antennal lobe defects in sema1a knockdown fourth instar larvae. These findings, which correlated with a larval odorant tracking behavioral phenotype, identified previously unreported roles for Sema1a in the developing insect larval olfactory system. Analysis of sema1a knockdown pupae also revealed a number of olfactory phenotypes, including olfactory receptor neuron targeting and projection neuron defects coincident with a collapse in the structure and shape of the antennal lobe and individual glomeruli. This study, which is to our knowledge the first functional genetic analysis of insect olfactory development outside of D. melanogaster, identified critical roles for Sema1a during Ae. aegypti larval and pupal olfactory development and advocates the use of chitosan/siRNA nanoparticles as an effective means of targeting genes during post-embryonic Ae. aegypti development. Use of siRNA nanoparticle methodology to understand sensory developmental genetics in mosquitoes will provide insight into the evolutionary conservation and divergence of key developmental genes which could be exploited in the development of both common and species-specific means for intervention.
Engineering bioactive nanoparticles to rejuvenate vascular progenitor cells
(Springer Nature, 2022-06-29) Bui, Loan; Edwards, Shanique; Hall, Eva; Alderfer, Laura; Round, Kellen; Owen, Madeline; Sainaghi, Pietro; Zhang, Siyuan; Nallathamby, Prakash D.; Haneline, Laura S.; Hanjaya-Putra, Donny; Pediatrics, School of Medicine
Fetal exposure to gestational diabetes mellitus (GDM) predisposes children to future health complications including type-2 diabetes mellitus, hypertension, and cardiovascular disease. A key mechanism by which these complications occur is through stress-induced dysfunction of endothelial progenitor cells (EPCs), including endothelial colony-forming cells (ECFCs). Although several approaches have been previously explored to restore endothelial function, their widespread adoption remains tampered by systemic side effects of adjuvant drugs and unintended immune response of gene therapies. Here, we report a strategy to rejuvenate circulating vascular progenitor cells by conjugation of drug-loaded liposomal nanoparticles directly to the surface of GDM-exposed ECFCs (GDM-ECFCs). Bioactive nanoparticles can be robustly conjugated to the surface of ECFCs without altering cell viability and key progenitor phenotypes. Moreover, controlled delivery of therapeutic drugs to GDM-ECFCs is able to normalize transgelin (TAGLN) expression and improve cell migration, which is a critical key step in establishing functional vascular networks. More importantly, sustained pseudo-autocrine stimulation with bioactive nanoparticles is able to improve in vitro and in vivo vasculogenesis of GDM-ECFCs. Collectively, these findings highlight a simple, yet promising strategy to rejuvenate GDM-ECFCs and improve their therapeutic potential. Promising results from this study warrant future investigations on the prospect of the proposed strategy to improve dysfunctional vascular progenitor cells in the context of other chronic diseases, which has broad implications for addressing various cardiovascular complications, as well as advancing tissue repair and regenerative medicine.
Functional Effects of Nanoparticle Exposure on Calu-3 Airway Epithelial Cells
(2012) Banga, Amiraj; Witzmann, Frank A.; Petrache, Horia I.; Blazer-Yost, Bonnie
High concentrations of manufactured carbon nanoparticles (CNP) are known to cause oxidative stress, inflammatory responses and granuloma formation in respiratory epithelia. To examine the effects of lower, more physiologically relevant concentrations, the human airway epithelial cell line, Calu-3, was used to evaluate potential alterations in transepithelial permeability and cellular function of airway epithelia after exposure to environmentally realistic concentrations of carbon nanoparticles. Three common carbon nanoparticles, fullerenes, single- and multi-wall carbon nanotubes (SWCNT, MWCNT) were used in these experiments. Electrophysiological measurements were performed to assay transepithelial electrical resistance (TEER) and epinephrine-stimulated chloride (Cl(-)) ion secretion of epithelial cell monolayers that had been exposed to nanoparticles for three different times (1 h, 24 h and 48 h) and over a 7 log unit range of concentrations. Fullerenes did not have any effect on the TEER or stimulated ion transport. However, the carbon nanotubes (CNT) significantly decreased TEER and inhibited epinephrine-stimulated Cl(-) secretion. The changes were time dependent and at more chronic exposures caused functional effects which were evident at concentrations substantially lower than have been previously examined. The functional changes manifested in response to physiologically relevant exposures would inhibit mucociliary clearance mechanisms and compromise the barrier function of airway epithelia.
IL-9 Intrinsically Alters Gene Expression and Chromatin Structure in Pulmonary Macrophages to Enhance Lung Tumor Growth
(2025-04) Cannon, Anthony Michael; Kaplan, Mark H.; Jerde, Travis; Brutkiewicz, Randy; Snell, Laura
Tumor-associated macrophages are an abundant, tumor-infiltrating cell population that support tumor progression through mechanisms such as extracellular matrix remodeling, immunosuppression, and metabolic reprogramming. The cytokine milieu is a factor that influences the functional phenotype of TAMs within the tumor microenvironment. Among these, interleukin-9 (IL-9) is a pleiotropic cytokine with both tumor-promoting and tumor-suppressing roles depending on the cancer type and responding cell. Importantly, mechanistic understanding of IL-9 in cancer is largely undefined. The work described in this thesis mechanistically defines the role of IL-9-responsive macrophages in the progression and metastasis of lung tumors. We demonstrate that IL-9 expands lung interstitial macrophage populations and induces the expression of Arginase 1 (ARG1), a critical enzyme in arginine to polyamine metabolism that is associated with poor survival in patients. Therapeutically, targeting ARG1-expressing macrophages using Arg1 siRNA-loaded nanoparticles significantly reduced polyamine levels and tumor burden. Additionally, bulk RNA sequencing and single-nuclei multi-modal ATAC and RNA sequencing in mixed-bone marrow chimeric mice revealed that IL-9 intrinsically reprograms the epigenetic and transcriptomic landscape of lung interstitial macrophages. Dysregulation of key genes, including Pdl1 and several cathepsins (Ctsd, Ctse, and Ctss), was identified and linked to increased tumor growth and an impaired anti-tumor immune response. In summary, this work identifies a critical vii pro-tumor mechanism of IL-9 in lung interstitial macrophages, characterized by dysregulated arginine metabolism, altered macrophage gene expression, and reduced anti-tumor immune responses. These findings underscore the potential of targeting IL-9-mediated pathways in macrophages as a potential therapeutic approach in lung cancer and metastasis.
In Vivo Wireless Brain Stimulation via Non-invasive and Targeted Delivery of Magnetoelectric Nanoparticles
(Springer, 2021) Nguyen, Tyler; Gao, Jianhua; Wang, Ping; Nagesetti, Abhignyan; Andrews, Peter; Masood, Sehban; Vriesman, Zoe; Liang, Ping; Khizroev, Sakhrat; Jin, Xiaoming; Anatomy, Cell Biology and Physiology, School of Medicine
Wireless and precise stimulation of deep brain structures could have important applications to study intact brain circuits and treat neurological disorders. Herein, we report that magnetoelectric nanoparticles (MENs) can be guided to a targeted brain region to stimulate brain activity with a magnetic field. We demonstrated the nanoparticles' capability to reliably evoke fast neuronal responses in cortical slices ex vivo. After fluorescently labeled MENs were intravenously injected and delivered to a targeted brain region by applying a magnetic field gradient, a magnetic field of low intensity (350-450 Oe) applied to the mouse head reliably evoked cortical activities, as revealed by two-photon and mesoscopic imaging of calcium signals and by an increased number of c-Fos expressing cells after stimulation. Neither brain delivery of MENs nor the magnetic stimulation caused significant increases in astrocytes and microglia. Thus, MENs could enable a non-invasive and contactless deep brain stimulation without the need of genetic manipulation.

Browsing by Subject "Nanoparticles"

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