scholarly journals Hybrid Biopolymer and Lipid Nanoparticles with Improved Transfection Efficacy for mRNA

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2034 ◽  
Author(s):  
Christian D. Siewert ◽  
Heinrich Haas ◽  
Vera Cornet ◽  
Sara S. Nogueira ◽  
Thomas Nawroth ◽  
...  

Hybrid nanoparticles from lipidic and polymeric components were assembled to serve as vehicles for the transfection of messenger RNA (mRNA) using different portions of the cationic lipid DOTAP (1,2-Dioleoyl-3-trimethylammonium-propane) and the cationic biopolymer protamine as model systems. Two different sequential assembly approaches in comparison with a direct single-step protocol were applied, and molecular organization in correlation with biological activity of the resulting nanoparticle systems was investigated. Differences in the structure of the nanoparticles were revealed by thorough physicochemical characterization including small angle neutron scattering (SANS), small angle X-ray scattering (SAXS), and cryogenic transmission electron microscopy (cryo-TEM). All hybrid systems, combining lipid and polymer, displayed significantly increased transfection in comparison to lipid/mRNA and polymer/mRNA particles alone. For the hybrid nanoparticles, characteristic differences regarding the internal organization, release characteristics, and activity were determined depending on the assembly route. The systems with the highest transfection efficacy were characterized by a heterogenous internal organization, accompanied by facilitated release. Such a system could be best obtained by the single step protocol, starting with a lipid and polymer mixture for nanoparticle formation.

1998 ◽  
Vol 111 (8) ◽  
pp. 1071-1080 ◽  
Author(s):  
S.M. Reuver ◽  
C.C. Garner

Members of the SAP family of synapse-associated proteins have recently emerged as central players in the molecular organization of synapses. In this study, we have examined the mechanism that localizes one member, SAP97, to sites of cell-cell contact. Utilizing epithelial CACO-2 cells and fibroblast L-cells as model systems, we demonstrate that SAP97 is associated with the submembranous cortical cytoskeleton at cell-cell adhesion sites. Furthermore, we show that its localization into this structure is triggered by E-cadherin. Although SAP97 can be found in an E-cadherin/catenin adhesion complex, this interaction seems to be mediated by the attachment of SAP97 to the cortical cytoskeleton. Our results are consistent with a model in which SAP97 is recruited to sites of cell-cell contact via an E-cadherin induced assembly of the cortical cytoskeleton.


2006 ◽  
Vol 969 ◽  
Author(s):  
Muhammet S Toprak ◽  
Brandon J McKenna ◽  
Herb Waite ◽  
Galen D Stucky

AbstractThe synthesis of organic and inorganic nano- and microspheres has attracted much interest for a variety of applications ranging from drug delivery to chemical storage and catalysis. We recently demonstrated the assembly of magnetic nanoparticles and polycations into hybrid microspheres in a single-step synthesis via complex coacervation. These microspheres showed viability for bio-applications as indicated by toxicity tests, and are therefore potential targeted drug delivery devices, as they can be directed magnetically. This work reports the recent progress on the potential use of these assemblies in drug release by controlling their porosity. Fluorescein tagged dextran molecules with different MW have been infiltrated into these entities to determine critical pore size by confocal fluorescence microscopy. Different physicochemical characterization results are also presented.


1992 ◽  
Vol 72 (1) ◽  
pp. 31-42 ◽  
Author(s):  
D. L. Burton ◽  
W. B. McGill

We compared changes in components of the N-mineralization cascade ranging from the very specific, such as a deaminase, to the highly integrated, such as biomass in a Black Chernozemic seeded to barley (Hordeum vulgare L.) under field conditions at Edmonton. Changes in enzyme content were related to soil [Formula: see text] to determine if the microbial environment changed sufficiently to exert feedback control on N mineralizing reactions and thereby to be detected. Histidase and protease were chosen as model systems for depolymerization and deamination respectively because information exists on their control in pure culture studies, on histidine content and control of histidase in soil, and assay procedures are available for soils. We observed an inverse relationship of labile histidase activity with [Formula: see text] in soils with high [Formula: see text] content and low [Formula: see text] ratio. This relationship provides indirect evidence for [Formula: see text] control of histidase content, but emphasizes that it is only one element of a complex control mechanism. Conversely, enzyme content was not rate limiting to net N mineralization, or sensitive to common control mechanisms. Biomass-C, an integrative measure of substrate supply, potential biological activity and enzymatic activity, describes net mineral-N production better than do indices of any single step. Regular spatial variability is exhibited by [Formula: see text] (and [Formula: see text]). [Formula: see text] is a product of mineralization; a substrate for immobilization, nitrification, plant uptake, and other reactions; and may also be a regulator of activity, or synthesis, of some enzymes. It is intriguing that none of the variables that influence mineral N, such as enzyme activity, biomass, or respiration, varied spatially in a statistically identifiable manner, yet [Formula: see text] did. Key words: Nitrogen mineralization, enzyme content, biomass, protease, histidase, ammonium regulation


Nanoscale ◽  
2014 ◽  
Vol 6 (7) ◽  
pp. 3532-3535 ◽  
Author(s):  
Maria Benelmekki ◽  
Murtaza Bohra ◽  
Jeong-Hwan Kim ◽  
Rosa E. Diaz ◽  
Jerome Vernieres ◽  
...  

Ternary hybrid nanoparticles composed of multiple dumbbell-like magneto-plasmonic FeAg cores encapsulated by a Si shell have been fabricated using a single-step co-sputter gas-condensation technique.


ACS Omega ◽  
2018 ◽  
Vol 3 (3) ◽  
pp. 3340-3347 ◽  
Author(s):  
Hui-Fen Chen ◽  
Mei-Jou Hung ◽  
Tzu-Hsin Hung ◽  
Ya-Wen Tsai ◽  
Chun-Wei Su ◽  
...  

ACS Nano ◽  
2012 ◽  
Vol 6 (6) ◽  
pp. 4955-4965 ◽  
Author(s):  
Xian-Zhu Yang ◽  
Shuang Dou ◽  
Yu-Cai Wang ◽  
Hong-Yan Long ◽  
Meng-Hua Xiong ◽  
...  

2018 ◽  
Vol 19 (11) ◽  
pp. 3670 ◽  
Author(s):  
Elisa Martella ◽  
Claudia Ferroni ◽  
Andrea Guerrini ◽  
Marco Ballestri ◽  
Marta Columbaro ◽  
...  

Osteosarcoma therapy might be moving toward nanotechnology-based drug delivery systems to reduce the cytotoxicity of antineoplastic drugs and improve their pharmacokinetics. In this paper, we present, for the first time, an extensive chemical and in vitro characterization of dual-loaded photo- and chemo-active keratin nanoparticles as a novel drug delivery system to treat osteosarcoma. The nanoparticles are prepared from high molecular weight and hydrosoluble keratin, suitably functionalized with the photosensitizer Chlorin-e6 (Ce6) and then loaded with the chemotherapeutic drug Paclitaxel (PTX). This multi-modal PTX-Ce6@Ker nanoformulation is prepared by both drug-induced aggregation and desolvation methods, and a comprehensive physicochemical characterization is performed. PTX-Ce6@Ker efficacy is tested on osteosarcoma tumor cell lines, including chemo-resistant cells, using 2D and 3D model systems. The single and combined contributions of PTX and Ce6 is evaluated, and results show that PTX retains its activity while being vehiculated through keratin. Moreover, PTX and Ce6 act in an additive manner, demonstrating that the combination of the cytostatic blockage of PTX and the oxidative damage of ROS upon light irradiation have a far superior effect compared to singularly administered PTX or Ce6. Our findings provide the proof of principle for the development of a novel, nanotechnology-based drug delivery system for the treatment of osteosarcoma.


Sign in / Sign up

Export Citation Format

Share Document