Browsing by Subject "Nanoparticle"

Now showing 1 - 10 of 12
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    Advances in Therapeutic L-Nucleosides and L-Nucleic Acids with Unusual Handedness
    (MDPI, 2021-12-24) Dantsu, Yuliya; Zhang, Ying; Zhang, Wen; Biochemistry and Molecular Biology, School of Medicine
    Nucleic-acid-based small molecule and oligonucleotide therapies are attractive topics due to their potential for effective target of disease-related modules and specific control of disease gene expression. As the non-naturally occurring biomolecules, modified DNA/RNA nucleoside and oligonucleotide analogues composed of L-(deoxy)riboses, have been designed and applied as innovative therapeutics with superior plasma stability, weakened cytotoxicity, and inexistent immunogenicity. Although all the chiral centers in the backbone are mirror converted from the natural D-nucleic acids, L-nucleic acids are equipped with the same nucleobases (A, G, C and U or T), which are critical to maintain the programmability and form adaptable tertiary structures for target binding. The types of L-nucleic acid drugs are increasingly varied, from chemically modified nucleoside analogues that interact with pathogenic polymerases to nanoparticles containing hundreds of repeating L-nucleotides that circulate durably in vivo. This article mainly reviews three different aspects of L-nucleic acid therapies, including pharmacological L-nucleosides, Spiegelmers as specific target-binding aptamers, and L-nanostructures as effective drug-delivery devices.
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    Delivery of nanoparticles to brain metastases of breast cancer using a cellular Trojan horse
    (Springer, 2012) Choi, Mi-Ran; Bardhan, Rizia; Stanton-Maxey, Katie J.; Badve, Sunil; Nakshatri, Harikrishna; Stantz, Keith M.; Cao, Ning; Halas, Naomi J.; Clare, Susan E.
    As systemic cancer therapies improve and are able to control metastatic disease outside the central nervous system, the brain is increasingly the first site of relapse. The blood–brain barrier (BBB) represents a major challenge to the delivery of therapeutics to the brain. Macrophages originating from circulating monocytes are able to infiltrate brain metastases while the BBB is intact. Here, we show that this ability can be exploited to deliver both diagnostic and therapeutic nanoparticles specifically to experimental brain metastases of breast cancer.
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    Effect of Curcumin-loaded Photoactivatable Polymeric Nanoparticle on peri-implantitis-related biofilm
    (2022) Tonon, Caroline Coradi; Panariello, Beatriz; Chorilli, Marlus; Spolidorio, Denise Madalena Palomari; Duarte, Simone; Biomedical and Applied Sciences, School of Dentistry
    Curcumin has been used as a photosensitizer (PS) for antimicrobial photodynamic chemotherapy (PACT). However, its low solubility, instability and poor bioavailability are a challenge for its in vivo application. This study aimed to synthesize curcumin-loaded polymeric nanoparticles (curcumin-NP) and to determine their antimicrobial and cytotoxic effects. Nanoparticles (NP) were synthesized by the nanoprecipitation method using polyprolactone as a polymer. Curcumin-NP was characterized by particle size, polydispersity index and zeta potential, scanning electron microscopy and curcumin encapsulation efficiency (EE). Curcumin-NP was compared to free curcumin solubilized in 10% DMSO as photosensitizers for PACT in single and multi-species Porphyromonas gingivalis, Fusobacterium nucleatum and Streptococcus oralis biofilms. Chlorhexidine 0.12% (CHX) and ultrapure water were used as positive and negative controls, respectively. The cytotoxic effect of curcumin-NP was evaluated on human periodontal ligament fibroblast cells (HPLF). Data were analyzed by ANOVA (α=0.05). Curcumin-NP exhibited homogeneity and stability in solution, small particle size and 67.5% EE of curcumin. Curcumin-NP presented antibiofilm activity at 500 µg/ml when photoactivated. Curcumin-NP and curcumin with and without photoactivation were not cytotoxic to HPLF cells. Curcumin-NP has antimicrobial and antibiofilm properties, with better effects when associated with blue-light, being a promising therapy for preventing and treating peri-implant diseases.
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    Electroceutical Fabric Lowers Zeta Potential and Eradicates Coronavirus Infectivity upon Contact
    (2020-05-15) Sen, Abhishek; Khona, Dolly; Ghatak, Subhadip; Gopalakrishnan, Vinoj; Cornetta, Kenneth; Roy, Sashwati; Khanna, Savita; Sen, Chandan; Surgery, School of Medicine
    Coronavirus with intact infectivity attached to PPE surfaces pose significant threat to the spread of COVID-19. We tested the hypothesis that an electroceutical fabric, generating weak potential difference of 0.5V, disrupts the infectivity of coronavirus upon contact by destabilizing the electrokinetic properties of the virion. Respiratory coronavirus particles (105) were placed in direct contact with the fabric for 1 or 5 minutes. Viral particles (2.5-4x104) were recovered from the fabric. Following one minute of contact, zeta potential of the coronavirus was significantly lowered indicating destabilization of its electrokinetic properties. Size-distribution plot showed appearance of aggregation of the virus. Testing of the cytopathic effects of the virus showed eradication of infectivity as quantitatively assessed by PI-calcein and MTT cell viability tests. This work provides the rationale to consider the studied electroceutical fabric, or other materials with comparable property, as material of choice for the development of PPE in the fight against COVID-19.
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    Inhibition of IFNAR-JAK signaling enhances tolerability and transgene expression of systemic non-viral DNA delivery
    (Elsevier, 2025-03-05) Senapati, Sujata; Bertolini, Thais B.; Minnier, Michael A.; Yazicioglu, Mustafa N.; Markusic, David M.; Zhang, Rui; Wicks, Joan; Nahvi, Ali; Herzog, Roland W.; Walsh, Matthew C.; Cejas, Pedro J.; Armour, Sean M.; Pediatrics, School of Medicine
    Lipid nanoparticles (LNPs) have demonstrated significant therapeutic value for non-viral delivery of mRNA and siRNA. While there is considerable interest in utilizing LNPs for delivering DNA (DNA-LNPs) to address a broad range of genetic disorders, acute inflammatory responses pose significant safety concerns and limit transgene expression below therapeutically relevant levels. However, the mechanisms and immune signaling pathways underlying DNA-LNP-triggered inflammatory responses are not well characterized. Through the use of gene-targeted mouse models, we have identified cGAS-STING and interferon-α/β receptor (IFNAR) pathways as major mediators of acute inflammation triggered by systemic delivery of DNA-LNPs. cGAS-STING activation induces expression of numerous JAK-STAT-activating cytokines, and we show that treatment of mice with the JAK inhibitors ruxolitinib or baricitinib significantly improves tolerability to systemically delivered DNA-LNPs. Furthermore, specific inhibition of IFNAR signaling enhances both DNA-LNP tolerability and transgene expression. Utilization of JAK inhibitors or IFNAR blockade represent promising strategies for enhancing the safety and efficacy of non-viral DNA delivery for gene therapy.
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    Magneto-Electric Nanoparticles Cobalt Ferrite (CoFe2O4) -- Barium Titanate (BaTiO3) for Non-Invasive Neural Modulations
    (2020-09) Nguyen, Tyler; White, Fletcher; Blesch, Armin; Jin, Xiaoming; Rodgers, Richard; Khizroev, Sakhrat
    Non-invasive brain stimulation is valuable for studying neural circuits and treating various neurological disorders in human. However, current technologies of noninvasive brain stimulation usually have low spatial and temporal precision and poor brain penetration, which greatly limit their application. A new class of nanoparticles known as magneto-electric nanoparticles (MENs) is highly efficient in coupling an externally applied magnetics wave with generating local electric fields for neuronal activity modulation. Here, a new type of MENs was developed that consisted of CoFe2O4- BaTiO3 and had excellent magneto-electrical coupling properties. Calcium imaging technique was used to demonstrate their efficacy in evoking neuronal activity in organotyic and acute cortical slices that expressed GCaMP6 protein. For in vivo noninvasive delivery of MENs to brain, fluorescently labeled MENs were intravenously injected and attracted to pass through blood brain barrier to a targeted brain region by applying a focal magnet field. Magnetic wave (~450 G at 10 Hz) applied to mouse brain was able to activate cortical network activity, as revealed by in vivo two-photon and mesoscopic imaging of calcium signals at both cellular and global network levels. The effect was further confirmed by the increased number of c-Fos expressing cells after magnetic stimulation. Histological analysis indicated that neither brain delivery of MENs nor the subsequent magnetic stimulation caused any significant increases in the numbers of GFAP and IBA1 positive astrocytes and microglia in the brain. MENs stimulation also show high efficacy in short-term pain relieve when tested with a tibial nerve injury mouse model. The study demonstrates the feasibility of using MENs as a novel efficient and non-invasive technique of brain stimulation, which may have great potential for translation.
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    Metformin-Loaded Nanospheres Laden Photocrosslinkable Gelatin Hydrogel for Bone Tissue Engineering
    (Elsevier, 2021) Qu, Liu; Dubey, Nileshkumar; Ribeiro, Juliana S.; Bordini, Ester A. F.; Ferreira, Jessica A.; Xu, Jinping; Castilho, Rogerio M.; Bottino, Marco C.; Biomedical and Applied Sciences, School of Dentistry
    The aim of this investigation was to engineer metformin (MF)-loaded mesoporous silica nanospheres (MSNs)-laden gelatin methacryloyl (GelMA) photocrosslinkable hydrogels and test their effects on the mechanical properties, swelling ratio, drug release, cytocompatibility, and osteogenic differentiation of stem cells from human exfoliated deciduous teeth (SHEDs). As-received and carboxylated MSNs (MSNs-COOH) were characterized by scanning and transmission electron microscopies (SEM and TEM), as well as Fourier-transform infrared spectroscopy (FTIR) prior to hydrogel modification. MF-MSNs-COOH were obtained by loading MF into MSNs at a 1:1 mass ratio. Upon MSNs-COOH laden-hydrogels fabrication, the mechanical properties, swelling ratio and MF release were evaluated. SHEDs were seeded on the hydrogels and cytocompatibility was examined. The effects of the MF-MSNs-COOH/GelMA on the osteogenic differentiation of SHEDs were measured by ALP activity, Alizarin Red assay, and Real-time PCR. Statistics were performed using one-way ANOVA (α = 0.05). Morphological (SEM and TEM) analyses of pristine and carboxylated MSNs revealed a mean particle size of 200 nm and 218 nm, respectively. Importantly, an intrinsic nanoporous structure was noticed. Incorporation of MSNs-COOH at 1.5 mg/mL in GelMA led to the highest compressive modulus and swelling ratio. The addition of MSNs-COOH (up to 3 mg/mL) in GelMA did not impact cell viability. The presence of MF in MSNs-COOH/GelMA significantly promoted cell proliferation. Significant upregulation of osteogenic-related genes (except OCN) were seen for modified (MSNs-COOH and MF-MSNs-COOH) hydrogels when compared to GelMA. Altogether, the engineered MF-MSNs-COOH/GelMA shows great promise in craniomaxillofacial applications as an injectable, cell-free and bioactive therapeutics for bone regeneration.
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    Modeling of external self-excitation and force generation on magnetic nanoparticles inside vitreous cavity
    (AIMS Press, 2021) Parker, Evan; Mitchell, Chandler S.; Smith, Joshua P.; Carr, Evan; Akbari, Rasul; Izadian, Afshin; Hajrasouliha, Amir R.; Ophthalmology, School of Medicine
    The purpose of this manuscript was to design a better method for recovery from rhegmatogenous retinal detachment (RRD) surgery. We attempted to achieve this by designing a helmet that can manipulate intraocular magnetic nanoparticles (MNPs) and create a magnetic tamponade, eliminating the need for postoperative head positioning. A simulated analysis was developed to predict the pattern of magnetic force applied to the magnetic nanoparticles by external magnetic field. No participants were involved in this study. Instead, magnetic flux and force data for three different helmet designs were collected using virtual simulation tools. A prototype helmet was then constructed and magnetic flux and force data were recorded and compared to virtual data. For both virtual and physical scenarios, magnitude and direction of the resulting forces were compared to determine which design created the controlled direction and strongest forces into the back of the eye. Of the three virtual designs, both designs containing a visor had greater force magnitude than magnet alone. Between both designs with visors, the visor with bends resulted in forces more directed at the back of the eye. The physical prototype helmet shared similar measurements to virtual simulation with minimal percent error (Average = 5.47%, Standard deviation = 0.03). Of the three designs, the visor with bends generated stronger forces directed at the back of the eye, which is most appropriate for creating a tamponade on the retina. We believe that this design has shown promising capability for manipulating intraocular MNPs for the purpose of creating a tamponade for RRD.
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    Modular Nanoparticles for Selective Cell Targeting
    (2019-05) Peuler, Kevin; Lin, Chien-Chi; Agarwal, Mangilal; Veronesi, Michael C.
    Nanoparticles (NPs) are an emerging technology in biomedical engineering with opportunities in diagnostics, imaging, and drug delivery. NPs can be prepared from a wide range of organic and/or inorganic materials. They can be fabricated to exhibit different characteristics for biomedical applications. The goal of this thesis was to develop NPs with tunable surface properties for selective cell targeting. Specifically, polyelectrolyte complexes composed of heparin (Hep, a growth factor binding glycosaminoglycan) and poly-L-lysine (PLL, a homopolymeric lysine) were prepared via a pulse sonication method. The Hep/PLL core NPs were further layered with additional Hep, tetrazine (Tz) modified Hep, or dextran sulfate (DS). The addition of Tz handle on Hep backbone permitted easy modification of NP surface with norbornene (NB) modified motifs/ligands, including inert poly(ethylene glycol) (PEG), cell adhesive peptides (e.g., RGD), and/or fluorescent marker. Both Hep and DS coated NPs could be readily internalized by J774A.1 monocytes/macrophages, whereas PEGylated NPs effectively reduced cellular uptake/recognition. The versatility of this NP system was further demonstrated by laying DS on the Hep/PLL NP surface. DS-coated NPs were recognized by J774A.1 cells more effectively. Furthermore, DS-layered NPs seemed to reduce IL-10 production on a per cell basis, suggesting that these NPs could be used to alter polarization of macrophages.
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    Nanoparticle-Based Treatment Approaches for Skin Cancer: A Systematic Review
    (MDPI, 2023-07-25) Diaz, Michael Joseph; Natarelli, Nicole; Aflatooni, Shaliz; Aleman, Sarah J.; Neelam, Sphurti; Tran, Jasmine Thuy; Taneja, Kamil; Lucke-Wold, Brandon; Forouzandeh, Mahtab; Medicine, School of Medicine
    Nanoparticles have shown marked promise as both antineoplastic agents and drug carriers. Despite strides made in immunomodulation, low success rates and toxicity remain limitations within the clinical oncology setting. In the present review, we assess advances in drug delivery nanoparticles, for systemic and topical use, in skin cancer treatment. A systematic review of controlled trials, meta-analyses, and Cochrane review articles was conducted. Eligibility criteria included: (1) a primary focus on nanoparticle utility for skin cancer; (2) available metrics on prevention and treatment outcomes; (3) detailed subject population; (4) English language; (5) archived as full-text journal articles. A total of 43 articles were selected for review. Qualitative analysis revealed that nanoscale systems demonstrate significant antineoplastic and anti-metastasis properties: increased drug bioavailability, reduced toxicity, enhanced permeability and retention effect, as well as tumor growth inhibition, among others. Nanoformulations for skin cancers have largely lagged behind those tested in other cancers–several of which have commercialized formulae. However, emerging evidence has indicated a powerful role for these carriers in targeting primary and metastatic skin cancers.