RAFT Polymerization for the Synthesis of Tertiary Amine-Based Diblock Copolymer Nucleic Acid Delivery Vehicles

2017 ◽  
Vol 17 (12) ◽  
pp. 1700225 ◽  
Author(s):  
Annie K. McClellan ◽  
Taisen Hao ◽  
Tracy A. Brooks ◽  
Adam E. Smith
Keyword(s):  
Nucleic Acid ◽  
Tertiary Amine ◽  
Diblock Copolymer ◽  
Raft Polymerization ◽  
Nucleic Acid Delivery ◽  
Delivery Vehicles

scholarly journals Designer Materials for Nucleic Acid Delivery

MRS Bulletin ◽  
2005 ◽  
Vol 30 (9) ◽  
pp. 635-639 ◽  
Author(s):  
Theresa M. Reineke ◽  
Mark W. Grinstaff
Keyword(s):  
Nucleic Acid ◽  
Genome Project ◽  
Patient Specific ◽  
Nucleic Acid Delivery ◽  
Genetic Vaccine ◽  
Introductory Article ◽  
Future Challenges ◽  
Materials Research ◽  
Delivery Vehicles ◽  
The Many

AbstractThe Human Genome Project continues to reveal the genetic basis for numerous acquired and inherited diseases ranging from cancer, HIV, and heart disease to muscular dystrophy and hemophilia. With this wealth of information, the ability to design patient-specific drugs that alter the cellular machinery at the genetic level in a way that controls or treats a specific disease will increasingly become a reality. Designing nucleic acid drugs as well as engineering novel delivery vehicles that encapsulate and effectively transport genetic materials into cells provides an opportunity to enhance the understanding of disease mechanisms and may help treat or cure these diseases. This issue of MRS Bulletin on “Designer Materials for Nucleic Acid Delivery” explores the diverse materials—polymers, lipids, nanoparticles, biocompatible scaffolds, and engineered peptides—that are being evaluated for the intracellular delivery of nucleic acids. These synthetic delivery systems are actively being investigated for many research purposes that range from gene-based therapy, genetic vaccine, and RNA interference to gene function and cellular signaling studies. This area is currently being pursued by a broad group of academic, clinical, and industrial researchers at both the fundamental and applied level, motivated by the widespread implications for human health. In this introductory article, we provide a general tutorial to gene-based therapies and a brief overview of the many areas of materials research that are currently making a tremendous impact on this interdisciplinary field.We conclude with a discussion of the future challenges that materials researchers face in developing viable nucleic acid delivery vehicles.

scholarly journals Signal responsive transient coacervation in complex coacervate core micelles

2021 ◽  
Author(s):  
Reece W. Lewis ◽  
Benjamin Klemm ◽  
Mariano Macchione ◽  
Rienk Eelkema
Keyword(s):  
Nucleic Acid ◽  
Block Copolymers ◽  
Tertiary Amine ◽  
Salt Concentration ◽  
Reaction Network ◽  
Material Design ◽  
Nucleic Acid Delivery ◽  
Complex Coacervate ◽  
Complex Coacervate Core Micelles ◽  
Coacervate Phase

Triggered coacervate phase (de)stabilisation in complex coacervate core micelles (C3Ms) has traditionally been limited to changes in pH and salt concentration, limiting options in responsive C3M material design. To expand this toolbox, we have developed C3Ms, that, at constant physiological pH, assemble and disassemble by coupling to a chemical reaction network (CRN) driven by the conversion of electron deficient allyl acetates and thiol or amine nucleophiles. This CRN produces transient quaternization of tertiary amine-functionalised block copolymers, which can then form the complex coacervate phase. We demonstrate triggered C3M assembly using two different allyl acetates, resulting in dramatically different assembly rates from hours to days. These are applied in various combinations with selected nucleophiles, demonstrating sequential signal induced C3M formation and deformation, as well as transient non-equilibrium (de)formation. We expect that timed and signal-responsive control over coacervate phase formation at physiological pH will find application in nucleic acid delivery, nano reactors and protocell research.

Controlled PEGylation Crowdedness for Polymeric Micelles To Pursue Ligand-Specified Privileges as Nucleic Acid Delivery Vehicles

2017 ◽  
Vol 9 (10) ◽  
pp. 8455-8459 ◽  
Author(s):  
Xiyi Chen ◽  
Haifeng Gu ◽  
Jinjun Yang ◽  
Sudong Wu ◽  
Jun Liu ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Polymeric Micelles ◽  
Nucleic Acid Delivery ◽  
Delivery Vehicles

Self-Assembling Nucleic Acid Delivery Vehicles via Linear, Water-Soluble, Cyclodextrin-Containing Polymers

2004 ◽  
Vol 11 (2) ◽  
pp. 179-197 ◽  
Author(s):  
M. Davis ◽  
S. Pun ◽  
N. Bellocq ◽  
T. Reineke ◽  
S. Popielarski ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Water Soluble ◽  
Nucleic Acid Delivery ◽  
Self Assembling ◽  
Delivery Vehicles

scholarly journals Signal responsive transient coacervation in complex coacervate core micelles

2021 ◽  
Author(s):  
Reece W. Lewis ◽  
Benjamin Klemm ◽  
Mariano Macchione ◽  
Rienk Eelkema
Keyword(s):  
Nucleic Acid ◽  
Block Copolymers ◽  
Tertiary Amine ◽  
Salt Concentration ◽  
Reaction Network ◽  
Material Design ◽  
Nucleic Acid Delivery ◽  
Complex Coacervate ◽  
Complex Coacervate Core Micelles ◽  
Coacervate Phase

Triggered coacervate phase (de)stabilisation in complex coacervate core micelles (C3Ms) has traditionally been limited to changes in pH and salt concentration, limiting options in responsive C3M material design. To expand this toolbox, we have developed C3Ms, that, at constant physiological pH, assemble and disassemble by coupling to a chemical reaction network (CRN) driven by the conversion of electron deficient allyl acetates and thiol or amine nucleophiles. This CRN produces transient quaternization of tertiary amine-functionalised block copolymers, which can then form the complex coacervate phase. We demonstrate triggered C3M assembly using two different allyl acetates, resulting in dramatically different assembly rates from hours to days. These are applied in various combinations with selected nucleophiles, demonstrating sequential signal induced C3M formation and deformation, as well as transient non-equilibrium (de)formation. We expect that timed and signal-responsive control over coacervate phase formation at physiological pH will find application in nucleic acid delivery, nano reactors and protocell research.

Non-Viral Nucleic Acid Delivery: Key Challenges and Future Directions

2011 ◽  
Vol 8 (3) ◽  
pp. 235-244 ◽  
Author(s):  
Mahmoud Elsabahy ◽  
Adil Nazarali ◽  
Marianna Foldvari
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acid Delivery ◽  
Viral Nucleic Acid ◽  
Future Directions

Charge‐Conversion Strategies for Nucleic Acid Delivery

2021 ◽  
pp. 2011103
Author(s):  
Kingshuk Dutta ◽  
Ritam Das ◽  
Jewel Medeiros ◽  
Pintu Kanjilal ◽  
S. Thayumanavan
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acid Delivery

scholarly journals Well-defined single polymer nanoparticles for the antibody-targeted delivery of chemotherapeutic agents

2015 ◽  
Vol 6 (8) ◽  
pp. 1286-1299 ◽  
Author(s):  
D. D. Lane ◽  
D. Y. Chiu ◽  
F. Y. Su ◽  
S. Srinivasan ◽  
H. B. Kern ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Drug Delivery ◽  
Targeted Delivery ◽  
Raft Polymerization ◽  
Chemotherapeutic Agents ◽  
Polymer Nanoparticles ◽  
Drug Delivery Vehicles ◽  
Molecular Weights ◽  
Delivery Vehicles ◽  
Targeted Drug

Second generation polymeric brushes with molecular weights in excess of 106 Da were synthesize via RAFT polymerization for use as antibody targeted drug delivery vehicles.

scholarly journals Synthetic Histidine-Rich Peptides Inhibit Candida Species and Other Fungi In Vitro: Role of Endocytosis and Treatment Implications

2006 ◽  
Vol 50 (8) ◽  
pp. 2797-2805 ◽  
Author(s):  
Jingsong Zhu ◽  
Paul W. Luther ◽  
Qixin Leng ◽  
A. James Mixson
Keyword(s):  
Nucleic Acid ◽  
Antifungal Activity ◽  
Antifungal Agents ◽  
Fungal Growth ◽  
Nucleic Acid Delivery ◽  
Histatin 5 ◽  
Ph Buffering ◽  
Endosomal Acidification

ABSTRACT A family of histidine-rich peptides, histatins, is secreted by the parotid gland in mammals and exhibits marked inhibitory activity against a number of Candida species. We were particularly interested in the mechanism by which histidine-rich peptides inhibit fungal growth, because our laboratory has synthesized a variety of such peptides for drug and nucleic acid delivery. In contrast to naturally occurring peptides that are linear, peptides made on synthesizers can be varied with respect to their degrees of branching. Using this technology, we explored whether histidine-lysine (HK) polymers of different complexities and degrees of branching affect the growth of several species of Candida. Polymers with higher degrees of branching were progressively more effective against Candida albicans, with the four-branched polymer, H2K4b, most effective. Furthermore, H2K4b accumulated efficiently in C. albicans, which may indicate its ability to transport other antifungal agents intracellularly. Although H2K4b had greater antifungal activity than histatin 5, their mechanisms were similar. Toxicity in C. albicans induced by histatin 5 or branched HK peptides was markedly reduced by 4,4′-diisothiocyanato-stilbene-2,2′-disulfonate, an inhibitor of anion channels. We also determined that bafilomycin A1, an inhibitor of endosomal acidification, significantly decreased the antifungal activity of H2K4b. This suggests that the pH-buffering and subsequent endosomal-disrupting properties of histidine-rich peptides have a role in their antifungal activity. Moreover, the ability of the histidine component of these peptides to disrupt endosomes, which allows their escape from the lysosomal pathway, may explain why these peptides are both effective antifungal agents and nucleic acid delivery carriers.

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