scholarly journals Biomechanics and Thermodynamics of Nanoparticle Interactions with Plasma and Endosomal Membrane Lipids in Cellular Uptake and Endosomal Escape

Langmuir ◽  
2014 ◽  
Vol 30 (25) ◽  
pp. 7522-7532 ◽  
Author(s):  
Chiranjeevi Peetla ◽  
Shihua Jin ◽  
Jonathan Weimer ◽  
Adekunle Elegbede ◽  
Vinod Labhasetwar
Keyword(s):  
Cellular Uptake ◽  
Membrane Lipids ◽  
Endosomal Escape ◽  
Endosomal Membrane ◽  
Nanoparticle Interactions

scholarly journals Role of endosomal membrane lipids and NPC2 in cholesterol transfer and membrane fusion

2010 ◽  
Vol 51 (7) ◽  
pp. 1747-1760 ◽  
Author(s):  
Misbaudeen Abdul-Hammed ◽  
Bernadette Breiden ◽  
Matthew A. Adebayo ◽  
Jonathan O. Babalola ◽  
Günter Schwarzmann ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Membrane Lipids ◽  
Endosomal Membrane

Peptide-nucleic acid nanostructures for transfection

2012 ◽  
Vol 3 (3) ◽  
pp. 283-293 ◽  
Author(s):  
Burkhard Bechinger
Keyword(s):  
Nucleic Acid ◽  
Physicochemical Properties ◽  
Cellular Uptake ◽  
Peptide Nucleic Acid ◽  
Endosomal Escape ◽  
Medical Applications ◽  
Specific Cell ◽  
Charge Composition ◽  
Cell Surfaces ◽  
Intracellular Targeting

AbstractTo use nucleic acids in biomedical research and medical applications, these highly hydrophilic macromolecules have to be transported through the organism, targeted to specific cell surfaces, and have to cross cellular barriers. To this end, nanosized transfection complexes have been designed and several of them have been successfully tested. Here, the different steps of the transfection process and the particular optimization protocols are reviewed, including the physicochemical properties of such vectors (size, charge, composition), protection in serum, cellular uptake, endosomal escape, and intracellular targeting. The transfection process has been subdivided into separate steps and here special emphasis is given to peptides that have been designed to optimize these steps individually. Finally, complex devices encompassing a multitude of beneficial functionalities for transfection have been developed.

Imidazole-Bearing Polymeric Micelles for Enhanced Cellular Uptake, Rapid Endosomal Escape, and On-demand Cargo Release

2018 ◽  
Vol 19 (6) ◽  
pp. 2610-2619 ◽  
Author(s):  
Di Lu ◽  
Yang An ◽  
Simin Feng ◽  
Xiaodan Li ◽  
Aiping Fan ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Polymeric Micelles ◽  
Endosomal Escape ◽  
On Demand

Mechanisms of cellular uptake and endosomal escape of calcium-siRNA nanocomplexes

2016 ◽  
Vol 515 (1-2) ◽  
pp. 46-56 ◽  
Author(s):  
Matan Goldshtein ◽  
Efrat Forti ◽  
Emil Ruvinov ◽  
Smadar Cohen
Keyword(s):  
Cellular Uptake ◽  
Endosomal Escape

Peptide amphiphiles with multifunctional fragments promoting cellular uptake and endosomal escape as efficient gene vectors

2015 ◽  
Vol 3 (6) ◽  
pp. 1068-1078 ◽  
Author(s):  
Liang Luan ◽  
Qingbin Meng ◽  
Liang Xu ◽  
Zhao Meng ◽  
Husheng Yan ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Cellular Uptake ◽  
Transfection Efficiency ◽  
Endosomal Escape ◽  
Peptide Amphiphiles ◽  
Gene Delivery Vectors ◽  
Efficient Gene ◽  
Gene Vectors ◽  
Lipofectamine 2000

A series of peptides containing multiple functional fragments were designed as gene-delivery vectors with transfection efficiency comparable to Lipofectamine 2000.

scholarly journals Design of New Polyaspartamide Copolymers for siRNA Delivery in Antiasthmatic Therapy

Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 89 ◽  
Author(s):  
Emanuela Fabiola Craparo ◽  
Salvatore Emanuele Drago ◽  
Nicolò Mauro ◽  
Gaetano Giammona ◽  
Gennara Cavallaro
Keyword(s):  
Epithelial Cells ◽  
Cellular Uptake ◽  
Intracellular Transport ◽  
Sirna Delivery ◽  
Weight Ratio ◽  
Endosomal Escape ◽  
Bronchial Epithelial ◽  
Vitro Experiment ◽  
In Vitro Experiment

Here, a novel protonable copolymer was realized for the production of polyplexes with a siRNA (inhibitor of STAT6 expression in asthma), with the aim of a pulmonary administration. The polycation was synthesized by derivatization of α,β-poly(N-2-hydroxyethyl)d,l-aspartamide (PHEA) with 1,2-Bis(3-aminopropylamino)ethane (bAPAE) in proper conditions to obtain a PHEA-g-bAPAE graft copolymer with a derivatization degree in amine (DDbAPAE%) equal to 35 mol%. The copolymer showed a proper buffering behavior, i.e., ranging between pH 5 and 7.4, to potentially give the endosomal escape of the obtained polycations. In effect, an in vitro experiment demonstrated the effect on biological membranes of the copolymer on bronchial epithelial cells (16-HBE) strongly dependent on the pH of the medium, i.e., higher at pH 5. bAPAE-based copolymers were further obtained with an increasing pegylation degree, i.e., equal to 1.9, 2.7, and 4.4 mol%, respectively. All the obtained copolymers were able to complex siRNA at a N/P ratio that decreases as the pegylation degree increases. At the same time, the tendency of polyplexes to aggregate and the capability to interact with mucin also decreases as the pegylation in the copolymer increases. Gene silencing experiments on 16-HBE showed that these copolymers have a significant role in improving the intracellular transport of naked siRNA, where the presence of PEG does not seem to hinder the cellular uptake of polyplexes. The latter obtained at polymer/siRNA weight ratio (R) equal to 10 with PHEA-g-PEG(C)-g-bAPAE also seems to be not susceptible to the presence of mucin, avoiding the polyanionic exchange of complexed siRNA, thus showing adequate behavior to be used as an effective vector for siRNA.

Gold and silver nanoparticle interactions with human proteins: impact and implications in biocorona formation

2015 ◽  
Vol 3 (10) ◽  
pp. 2075-2082 ◽  
Author(s):  
Abhilash Sasidharan ◽  
Jim E. Riviere ◽  
Nancy A. Monteiro-Riviere
Keyword(s):  
Cellular Uptake ◽  
Silver Nanoparticle ◽  
Nanoparticle Interactions ◽  
Human Proteins

Metallic NP interaction with human proteins, biocorona formation and their impact on cellular uptake.

scholarly journals H9N2 Influenza Whole Inactivated Virus Combined with Polyethyleneimine Strongly Enhances Mucosal and Systemic Immunity after Intranasal Immunization in Mice

2015 ◽  
Vol 22 (4) ◽  
pp. 421-429 ◽  
Author(s):  
Tao Qin ◽  
Yinyan Yin ◽  
Lulu Huang ◽  
Qinghua Yu ◽  
Qian Yang
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Respiratory Tract ◽  
Cellular Uptake ◽  
Gene Transfection ◽  
Antibody Responses ◽  
Endosomal Escape ◽  
Adjuvant Activity ◽  
Subunit Vaccines ◽  
Mucosal Delivery

ABSTRACTInfluenza whole inactivated virus (WIV) is more immunogenic and induces protective antibody responses compared with other formulations, like split virus or subunit vaccines, after intranasal mucosal delivery. Polyethyleneimine (PEI), an organic polycation, is widely used as a reagent for gene transfection and DNA vaccine delivery. Although PEI recently has demonstrated potent mucosal adjuvant activity for viral subunit glycoprotein antigens, its immune activity with H9N2 WIV is not well demonstrated. Here, mice were immunized intranasally with H9N2 WIV combined with PEI, and the levels of local respiratory tract and systemic immune responses were measured. Compared to H9N2 WIV alone, antigen-specific IgA levels in the local nasal cavity, trachea, and lung, as well as levels of IgG and its subtypes (IgG1 and IgG2a) in the serum, were strongly enhanced with the combination. Similarly, the activation and proliferation of splenocytes were markedly increased. In addition, PEI is superior as an H9N2 WIV delivery system due to its ability to greatly increase the viral adhesion to mucosal epithelial cells and to enhance the cellular uptake and endosomal escape of antigens in dendritic cells (DCs) and further significantly activate DCs to mature. Taken together, these results provided more insights that PEI has potential as an adjuvant for H9N2 particle antigen intranasal vaccination.

scholarly journals Late Endosomal/Lysosomal Cholesterol Accumulation Is a Host Cell-Protective Mechanism Inhibiting Endosomal Escape of Influenza A Virus

mBio ◽  
2018 ◽  
Vol 9 (4) ◽  
Author(s):  
Alexander Kühnl ◽  
Agnes Musiol ◽  
Nicole Heitzig ◽  
Danielle E. Johnson ◽  
Christina Ehrhardt ◽  
...  
Keyword(s):  
Host Cell ◽  
Influenza A Virus ◽  
Influenza A ◽  
Membrane Lipids ◽  
Endosomal Escape ◽  
Host Cells ◽  
Protective Mechanism ◽  
Cholesterol Accumulation ◽  
Protective Function ◽  
Cell Defense

ABSTRACTTo transfer the viral genome into the host cell cytoplasm, internalized influenza A virus (IAV) particles depend on the fusion of the IAV envelope with host endosomal membranes. The antiviral host interferon (IFN) response includes the upregulation of interferon-induced transmembrane protein 3 (IFITM3), which inhibits the release of the viral content into the cytosol. Although IFITM3 induction occurs concomitantly with late endosomal/lysosomal (LE/L) cholesterol accumulation, the functional significance of this process is not well understood. Here we report that LE/L cholesterol accumulation itself plays a pivotal role in the early antiviral defense. We demonstrate that inducing LE/L cholesterol accumulation is antiviral in non-IFN-primed cells, restricting incoming IAV particles and impairing mixing of IAV/endosomal membrane lipids. Our results establish a protective function of LE/L cholesterol accumulation and suggest endosomal cholesterol balance as a possible antiviral target.IMPORTANCEWith annual epidemics occurring in all parts of the world and the risk of global outbreaks, influenza A virus (IAV) infections remain a major threat to public health. Infected host cells detect viral components and mount an interferon (IFN)-mediated response to restrict virus propagation and spread of infection. Identification of cellular factors and underlying mechanisms that establish such an antiviral state can provide novel strategies for the development of antiviral drugs. The contribution of LE/L cholesterol levels, especially in the context of the IFN-induced antiviral response, has remained controversial so far. Here, we report that accumulation of cholesterol in the LE/L compartment contributes to the IFN-induced host cell defense against incoming IAV. Our results establish cholesterol accumulation in LE/Lper seas a novel antiviral barrier and suggest the endosomal cholesterol balance as a putative druggable host cell factor in IAV infection.

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