scholarly journals Co-Delivery of mRNA and pDNA Using Thermally Stabilized Coacervate-Based Core-Shell Nanosystems

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1924
Author(s):  
Sarah S. Nasr ◽  
Sangeun Lee ◽  
Durairaj Thiyagarajan ◽  
Annette Boese ◽  
Brigitta Loretz ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Colloidal Stability ◽  
Transfection Efficiency ◽  
Thermal Stabilization ◽  
Shielding Effect ◽  
Core Shell ◽  
Nucleic Acid Delivery ◽  
Fluorescent Reporter ◽  
Shell System ◽  
Pharmaceutical Application

Co-delivery of different species of protein-encoding polynucleotides, e.g., messenger RNA (mRNA) and plasmid DNA (pDNA), using the same nanocarrier is an interesting topic that remains scarcely researched in the field of nucleic acid delivery. The current study hence aims to explore the possibility of the simultaneous delivery of mRNA (mCherry) and pDNA (pAmCyan) using a single nanocarrier. The latter is based on gelatin type A, a biocompatible, and biodegradable biopolymer of broad pharmaceutical application. A core-shell nanostructure is designed with a thermally stabilized gelatin–pDNA coacervate in its center. Thermal stabilization enhances the core’s colloidal stability and pDNA shielding effect against nucleases as confirmed by nanoparticle tracking analysis and gel electrophoresis, respectively. The stabilized, pDNA-loaded core is coated with the cationic peptide protamine sulfate to enable additional surface-loading with mRNA. The dual-loaded core-shell system transfects murine dendritic cell line DC2.4 with both fluorescent reporter mRNA and pDNA simultaneously, showing a transfection efficiency of 61.4 ± 21.6% for mRNA and 37.6 ± 19.45% for pDNA, 48 h post-treatment, whereas established commercial, experimental, and clinical transfection reagents fail. Hence, the unique co-transfectional capacity and the negligible cytotoxicity of the reported system may hold prospects for vaccination among other downstream applications.

scholarly journals The impact of anionic polymers on gene delivery: how composition and assembly help evading the toxicity-efficiency dilemma

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Friederike Richter ◽  
Katharina Leer ◽  
Liam Martin ◽  
Prosper Mapfumo ◽  
Jana I. Solomun ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Cell Viability ◽  
Colloidal Stability ◽  
Serum Proteins ◽  
Transfection Efficiency ◽  
Genetic Material ◽  
Endosomal Escape ◽  
Shielding Effect ◽  
Viral Gene ◽  
The Impact

AbstractCationic polymers have been widely studied for non-viral gene delivery due to their ability to bind genetic material and to interact with cellular membranes. However, their charged nature carries the risk of increased cytotoxicity and interaction with serum proteins, limiting their potential in vivo application. Therefore, hydrophilic or anionic shielding polymers are applied to counteract these effects. Herein, a series of micelle-forming and micelle-shielding polymers were synthesized via RAFT polymerization. The copolymer poly[(n-butyl acrylate)-b-(2-(dimethyl amino)ethyl acrylamide)] (P(nBA-b-DMAEAm)) was assembled into cationic micelles and different shielding polymers were applied, i.e., poly(acrylic acid) (PAA), poly(4-acryloyl morpholine) (PNAM) or P(NAM-b-AA) block copolymer. These systems were compared to a triblock terpolymer micelle comprising PAA as the middle block. The assemblies were investigated regarding their morphology, interaction with pDNA, cytotoxicity, transfection efficiency, polyplex uptake and endosomal escape. The naked cationic micelle exhibited superior transfection efficiency, but increased cytotoxicity. The addition of shielding polymers led to reduced toxicity. In particular, the triblock terpolymer micelle convinced with high cell viability and no significant loss in efficiency. The highest shielding effect was achieved by layering micelles with P(NAM-b-AA) supporting the colloidal stability at neutral zeta potential and completely restoring cell viability while maintaining moderate transfection efficiencies. The high potential of this micelle-layer-combination for gene delivery was illustrated for the first time.

scholarly journals Role of Lipid-Based and Polymer-Based Non-Viral Vectors in Nucleic Acid Delivery for Next-Generation Gene Therapy

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2866 ◽  
Author(s):  
Aniket Wahane ◽  
Akaash Waghmode ◽  
Alexander Kapphahn ◽  
Karishma Dhuri ◽  
Anisha Gupta ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Nucleic Acid ◽  
Messenger Rna ◽  
Viral Vectors ◽  
Cationic Lipids ◽  
Nucleic Acid Delivery ◽  
Nucleic Acid Analogs ◽  
Organ Specific ◽  
Interfering Rna

The field of gene therapy has experienced an insurgence of attention for its widespread ability to regulate gene expression by targeting genomic DNA, messenger RNA, microRNA, and short-interfering RNA for treating malignant and non-malignant disorders. Numerous nucleic acid analogs have been developed to target coding or non-coding sequences of the human genome for gene regulation. However, broader clinical applications of nucleic acid analogs have been limited due to their poor cell or organ-specific delivery. To resolve these issues, non-viral vectors based on nanoparticles, liposomes, and polyplexes have been developed to date. This review is centered on non-viral vectors mainly comprising of cationic lipids and polymers for nucleic acid-based delivery for numerous gene therapy-based applications.

Core‐Shell System Based on Gelatin and Poly(Vinyl Alcohol) (PVA) for Concrete Self‐Healing Applications: Synthesis, Characterization, and Optimization

2021 ◽  
Vol 398 (1) ◽  
pp. 2000194
Author(s):  
Vítor Corrêa da Costa ◽  
Fernando Gomes de Souza Junior ◽  
Luana de Castro Sousa ◽  
Kaushik Pal ◽  
Romildo Dias Tolêdo Filho
Keyword(s):  
Vinyl Alcohol ◽  
Poly Vinyl Alcohol ◽  
Core Shell ◽  
Self Healing ◽  
Shell System

A small heterobifunctional ligand provides stable and water dispersible core–shell CdSe/ZnS quantum dots (QDs)

Nanoscale ◽  
2018 ◽  
Vol 10 (42) ◽  
pp. 19720-19732 ◽  
Author(s):  
Gianluca Salerno ◽  
Simona Scarano ◽  
Marianna Mamusa ◽  
Marco Consumi ◽  
Stefano Giuntini ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Colloidal Stability ◽  
Core Shell ◽  
Water Dispersible

A small heterobifunctional ligand provides easy to handle and hydrophilic QDs with enhanced colloidal stability.

Colloidal Stability of Magnetite/Poly(lactic acid) Core/Shell Nanoparticles

Langmuir ◽  
2006 ◽  
Vol 22 (6) ◽  
pp. 2816-2821 ◽  
Author(s):  
Salvador A. Gómez-Lopera ◽  
José L. Arias ◽  
Visitación Gallardo ◽  
Ángel V. Delgado
Keyword(s):  
Lactic Acid ◽  
Colloidal Stability ◽  
Poly Lactic Acid ◽  
Core Shell ◽  
Shell Nanoparticles ◽  
Core Shell Nanoparticles

Surface Engineering of Magnetite Nanoparticles by Plant Protein: Investigation into Magnetic Properties

2016 ◽  
Vol 11 ◽  
pp. 38-44 ◽  
Author(s):  
Amlan Kumar Das ◽  
Avinash Marwal ◽  
Vikram Pareek ◽  
Yagya Joshi ◽  
Apoorva
Keyword(s):  
Magnetite Nanoparticles ◽  
Shell Structure ◽  
Colloidal Stability ◽  
Surface Engineering ◽  
Thermo Gravimetric Analysis ◽  
Magnetic Behaviour ◽  
Plant Protein ◽  
Core Shell ◽  
Gravimetric Analysis ◽  
Core Shell Structure

The surface of the magnetite nanoparticles has been engineered by the proteins available in the leaf extract of Datura inoxia. Fourier Transform Infrared (FTIR) study and by thermo gravimetric analysis (TGA) confirms the bonding between metal ions and the amide carbonyl group preset in the plant protein confirming the formation of core-shell structure. The plant protein coated magnetic Fe3O4 nanoparticles under investigation have an average size of about 14 nm (˂20nm). The isothermal magnetization curve of the ferrofluid appears in S-like sigmoid shape showing soft nonhysteretic magnetic behaviour at room temperature. The saturation magnetization (MS), remanent magnetization (MR), squareness (MR/MS) and coercivity value (HC) increased with decreasing temperature from 300 K to 10 K. The increment of magnetization (45 to 53 emu/gm) might be due to the decrease in thermal energy while the enhancement of coercivity (0-208 Oe) is attributed to the exchange interaction at the interface between the ferromagnetic (Fe3O4) and diamagnetic surface layer of protein on the nanocrystalline magnetite. The magnetization value is much smaller in comparison with the bulk magnetite (92emu/g) due to surface spin disorder also approves core-shell structure of diamagnetic protein layer on the surface. The results show the ease of the synthesis to reinforce the colloidal stability where the super paramagnetic behaviour has been found to be restored. The core-shell moiety could play an important role in biological systems as a means of storing Fe+3 for an organism.

Development of Non-Cadmium I-III-VI Quantum Dots and their Surface Modification for Biomedical Applications

2018 ◽  
Vol 915 ◽  
pp. 163-168 ◽  
Author(s):  
Xiao Shan Zhu ◽  
Violeta G. Demillo ◽  
Si Qi Chen ◽  
Athanasios G. Mamalis
Keyword(s):  
Thermal Decomposition ◽  
Mass Production ◽  
Biomedical Applications ◽  
Colloidal Stability ◽  
Specific Binding ◽  
Shell Structures ◽  
Core Shell ◽  
Human Brain Tumor ◽  
Brain Tumor Cells ◽  
Low Toxicity

I-III-VI QDs (CuInS2/ZnS or AgInS2/ZnS core/shell structures) possess low toxicity, and are a logical replacement for cadmium-based QDs for biomedical applications. Our synthesis of I-III-VI QDs is based on thermal decomposition of less toxic precursors and can be easily scaled up for mass production for sustainable and reliable imaging and sensing experiments. Through nonstoichiometric composition adjustment, we synthesized I-III-VI QDs with reliable and controllable optical properties, including high QYs and tunable photoluminescence. We also developed new zwitterionic amphiphiles and applied them to encapsulate I-III-VI QDs to achieve colloidal stability in proteinaceous solutions with wide pH/ionic ranges, low non-specific binding, and easily bio-conjugation. On the basis of these developments, we applied our I-III-VI QDs in cellular imaging to to specifically target human brain tumor cells.

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