An official website of the United States government
Colloidal quantum dots (CQDs) are promising materials for photovoltaic applications due to their solution processibility and size-dependent band gap tunability. The electron transport layer (ETL) is an important component of PbS CQD solar cells, and the quality of the zinc oxide nanoparticle (ZnO NP) ETL film significantly impacts both the power conversion efficiency (PCE) and fabrication yield of CQD solar cells. We report on multiple methods to improve the quality of ZnO NP ETL films and demonstrate increased PCE and device yield in standard CQD solar cells employing optimized ZnO NP films. We also discuss the application of these methods in an inverted CQD solar cell architecture.
more »
« less
Comparative Molecular Immunological Activity of Physiological Metal Oxide Nanoparticle and its Anticancer Peptide and RNA Complexes
Currently, there is a great interest in nanoparticle-based vaccine delivery. Recent studies suggest that nanoparticles when introduced into the biological milieu are not simply passive carriers but may also contribute immunological activity themselves or of their own accord. For example there is considerable interest in the biomedical applications of one of the physiologically-based inorganic metal oxide nanoparticle, zinc oxide (ZnO). Indeed zinc oxide (ZnO) NP are now recognized as a nanoscale chemotherapeutic or anticancer nanoparticle (ANP) and several recent reports suggest ZnO NP and/or its complexes with drug and RNA induce a potent antitumor response in immuno-competent mouse models. A variety of cell culture studies have shown that ZnO NP can induce cytokines such as IFN-γ, TNF-α, IL-2, and IL-12 which are known to regulate the tumor microenvironment. Much less work has been done on magnesium oxide (MgO), cobalt oxide (Co3O4), or nickel oxide (NiO); however, despite the fact that these physiologically-based metal oxide NP are reported to functionally load and assemble RNA and protein onto their surface and may thus also be of potential interest as nanovaccine platform. Here we initially compared in vitro immunogenicity of ZnO and Co3O4 NP and their effects on cancer-associated or tolerogenic cytokines. Based on these data we moved ZnO NP forward to testing in the ex vivo splenocyte assay relative to MgO and NiO NP and these data showed significant difference for flow cytometry sorted population for ZnO-NP, relative to NiO and MgO. These data suggesting both molecular and cellular immunogenic activity, a double-stranded anticancer RNA (ACR), polyinosinic:poly cytidylic acid (poly I:C) known to bind ZnO NP; when ZnO-poly I:C was injected into B16F10-BALB/C tumor significantly induced, IL-2 and IL-12 as shown by Cohen’s d test. LL37 is an anticancer peptide (ACP) currently in clinical trials as an intratumoral immuno-therapeutic agent against metastatic melanoma. LL37 is known to bind poly I:C where it is thought to compete for receptor binding on the surface of some immune cells, metastatic melanoma and lung cells. Molecular dynamic simulations revealed association of LL37 onto ZnO NP confirmed by gel shift assay. Thus using the well-characterized model human lung cancer model cell line (BEAS-2B), poly I:C RNA, LL37 peptide, or LL37-poly I:C complexes were loaded onto ZnO NP and delivered to BEAS-2B lung cells, and the effect on the main cancer regulating cytokine, IL-6 determined by ELISA. Surprisingly ZnO-LL37, but not ZnO-poly I:C or the more novel tricomplex (ZnO-LL37-poly I:C) significantly suppressed IL-6 by >98–99%. These data support the further evaluation of physiological metal oxide compositions, so-called physiometacomposite (PMC) materials and their formulation with anticancer peptide (ACP) and/or anticancer RNA (ACR) as a potential new class of immuno-therapeutic against melanoma and potentially lung carcinoma or other cancers.
more »
« less
- Award ID(s):
- 1726332
- PAR ID:
- 10210497
- Date Published:
- Journal Name:
- Nanomaterials
- Volume:
- 9
- Issue:
- 12
- ISSN:
- 2079-4991
- Page Range / eLocation ID:
- 1670
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
ABSTRACT This study investigates the morphological, thermal, mechanical, and bioactive properties of centrifugally spun fibrous composites made from poly(D,L‐lactide)/poly(3‐hydroxybutyrate) (PLA/PHB) blends with zinc oxide (ZnO) and hydroxyapatite (Hap) nanoparticles. A 75/25 PLA/PHB weight ratio was chosen to balance mechanical and thermal properties. The precursor solution viscosities ranged from 0.25 to 0.50 Pa s, increasing with nanoparticle incorporation probably due to polymer‐nanoparticle interactions. SEM revealed a uniform fibrous morphology, with diameters of 1.21 for PLA/PHB, 2.65 for PLA/ZnO/Hap, and 1.80 μm for PLA/PHB/ZnO/Hap. TGA showed two‐step degradation for PLA/PHB fibers, while PLA/PHB/ZnO/Hap degraded in a single step at 249°C, leaving a residue of 9.95%. DSC indicated partial miscibility, with cold crystallization at 85°C (enthalpy: 7.72 J/g), slightly modified by nanoparticle addition. PLA/PHB fibers achieved a Young's modulus of 24.96 ± 3.91 MPa, three times that of pure PLA, but adding ZnO and Hap reduced modulus and tensile strength to 6.03 and 0.29 MPa, retaining suitability for biomedical applications. PLA/PHB/ZnO/Hap fibers exhibited 90%Escherichia coligrowth inhibition and enhanced MC3T3‐E1 cell viability by 120% on day 7. These results highlight their potential for antimicrobial, biocompatible medical devices.more » « less
-
Nanoparticle drug-delivery systems (NP DDS) have proven to be tremendously impactful for delivering therapeutic agents in cancer treatments, vaccinations, gene therapy, and diagnostics, and enabled agents such as RNA therapeutics. However, the exposure of NP DDS to biological milieus leads to the rapid adsorption of proteins and other molecules, forming a proteinaceous corona that obscures NP surface characteristics and controls the biological interactions of the NP DDS. Surface modifications, including poly(ethylene glycol) (PEG) and synthetic zwitterionic polymers, reduce protein adsorption yet lack monomer-scale tunability, have off-target immunological effects, and suffer from targeting-limited steric hindrance, altogether motivating the development of alternative approaches. Peptides can uniquely form many zwitterions and have shown promise in reducing and controlling the NP protein corona as a function of the peptide sequence. However, the impact of zwitterionic peptides (ZIPs) on the drug-delivery properties of polymeric NPs has not been explored. In this work, diverse ZIPs computationally predicted to reduce protein adsorption by assessing peptide–peptide β-strand interaction energies were conjugated to pH-responsive cationic NPs. The resulting ZIP-NP conjugates exhibited up to 88% reduced protein adsorption and a range of siRNA-mediated gene knockdown that correlates with interaction energies. These data suggest that the peptide–peptide interaction energy is a promising design parameter for ZIPs for further model development. ZIP-NP also exhibited sequence-dependent variations in cellular uptake and circulation half-life, indicating that ZIP-NPs are suitable for tuning and improving NP drug-delivery characteristics.more » « less
-
Fusobacterium nucleatumis implicated in accelerating colorectal cancer (CRC) and is found within metastatic CRC cells in patient biopsies. Here, we found that bacterial invasion of CRC cells and cocultured immune cells induced a differential cytokine secretion that may contribute to CRC metastasis. We used a modified galactose kinase markerless gene deletion approach and found thatF. nucleatuminvaded cultured HCT116 CRC cells through the bacterial surface adhesin Fap2. In turn, Fap2-dependent invasion induced the secretion of the proinflammatory cytokines IL-8 and CXCL1, which are associated with CRC progression and promoted HCT116 cell migration. Conditioned medium fromF. nucleatum–infected HCT116 cells caused naïve cells to migrate, which was blocked by depleting CXCL1 and IL-8 from the conditioned medium. Cytokine secretion from HCT116 cells and cellular migration were attenuated by inhibitingF. nucleatumhost-cell binding and entry using galactose sugars,l-arginine, neutralizing membrane protein antibodies, orfap2deletion.F. nucleatumalso induces the mobilization of immune cells in the tumor microenvironment. However, in neutrophils and macrophages, the bacterial-induced secretion of cytokines was Fap2 independent. Thus, our findings show thatF. nucleatumboth directly and indirectly modulates immune and cancer cell signaling and migration. Because increased IL-8 and CXCL1 production in tumors is associated with increased metastatic potential and cell seeding, poor prognosis, and enhanced recruitment of tumor-associated macrophages and fibroblasts, we propose that inhibition of host-cell binding and invasion, potentially through vaccination or novel galactoside compounds, could be an effective strategy for reducingF. nucleatum–associated CRC metastasis.more » « less
-
Abstract Countless biophysical studies have sought distinct markers in the cellular mechanical response that could be linked to morphogenesis, homeostasis, and disease. Here, an iterative-fitting methodology visualizes the time-dependent viscoelastic behavior of human skin cells under physiologically relevant conditions. Past investigations often involved parameterizing elastic relationships and assuming purely Hertzian contact mechanics, which fails to properly account for the rich temporal information available. We demonstrate the performance superiority of the proposed iterative viscoelastic characterization method over standard open-search approaches. Our viscoelastic measurements revealed that 2D adherent metastatic melanoma cells exhibit reduced elasticity compared to their normal counterparts—melanocytes and fibroblasts, and are significantly less viscous than fibroblasts over timescales spanning three orders of magnitude. The measured loss angle indicates clear differential viscoelastic responses across multiple timescales between the measured cells. This method provides insight into the complex viscoelastic behavior of metastatic melanoma cells relevant to better understanding cancer metastasis and aggression.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3390/nano9121670
