Abstract:Poly(N-methylvinylamines) with secondary amines can form complexes with plasmid DNA (pDNA) and provide transfection efficiency in HeLa cells in the same order as linear polyethyleneimine but with higher cell viability. Chemical modifications of poly(N-methylvinylamine) backbones are performed to further improve transfection efficiency while maintaining low degree of cytotoxicity. In a first type of polymer, primary amino groups are incorporated via a copolymerization strategy. In a second one, primary amino an… Show more
“…The polymers did not present any cytotoxicity after removal of the cobalt complex. For example, PVAc/C 60 nanohybrids were hydrolyzed into water-soluble PVOH/C 60 and exploited in photodynamic cancer therapy applications. , Also, well-defined cobalt-free poly(vinyl amine)s resulting from hydrolysis of poly(vinyl amides) formed by CMRP demonstrated excellent cell viability and high potential for gene transfection. , …”
Organocobalt(III) complexes (R-Co III ), defined as cobalt complexes featuring a carbon−cobalt bond, are largely used to produce carbon-centered radicals by homolytic cleavage of their C−Co bond under mild conditions. They are key compounds in cutting-edge developments in the fields of organic chemistry, biochemistry, medical research, radical reactions, and organometallic chemistry. This is the first Review of the use of R-Co III in both organic and polymer chemistries. Although pioneering works in organic synthesis have largely contributed to the implementation of R-Co III in polymer design, the two fields have evolved independently, with many breakthroughs on both sides. The main motivation of this Review is to confront both fields to stimulate cross-fertilization. It notably describes the most important synthetic pathways for R-Co III , the influence of the ligand structure and the environment of the complex on the C−Co bond strength, the modes of formation of the radicals, and the most relevant R-Co III -promoted radical reactions, with a focus on the main reaction mechanisms. CONTENTS 6.4. Polymerizations 6938 7. Conclusions 6945 Author Information 6946 Corresponding Author 6946 ORCID 6946 Notes 6946 Biographies 6946 Acknowledgments 6946 References 6946
“…The polymers did not present any cytotoxicity after removal of the cobalt complex. For example, PVAc/C 60 nanohybrids were hydrolyzed into water-soluble PVOH/C 60 and exploited in photodynamic cancer therapy applications. , Also, well-defined cobalt-free poly(vinyl amine)s resulting from hydrolysis of poly(vinyl amides) formed by CMRP demonstrated excellent cell viability and high potential for gene transfection. , …”
Organocobalt(III) complexes (R-Co III ), defined as cobalt complexes featuring a carbon−cobalt bond, are largely used to produce carbon-centered radicals by homolytic cleavage of their C−Co bond under mild conditions. They are key compounds in cutting-edge developments in the fields of organic chemistry, biochemistry, medical research, radical reactions, and organometallic chemistry. This is the first Review of the use of R-Co III in both organic and polymer chemistries. Although pioneering works in organic synthesis have largely contributed to the implementation of R-Co III in polymer design, the two fields have evolved independently, with many breakthroughs on both sides. The main motivation of this Review is to confront both fields to stimulate cross-fertilization. It notably describes the most important synthetic pathways for R-Co III , the influence of the ligand structure and the environment of the complex on the C−Co bond strength, the modes of formation of the radicals, and the most relevant R-Co III -promoted radical reactions, with a focus on the main reaction mechanisms. CONTENTS 6.4. Polymerizations 6938 7. Conclusions 6945 Author Information 6946 Corresponding Author 6946 ORCID 6946 Notes 6946 Biographies 6946 Acknowledgments 6946 References 6946
“…Free radical polymerization has been utilized to yield different PVam structures, which increased transfection efficiencies slightly above PEI comparisons 29 . The same group utilized a secondary amine derivative of PVam for improved transfection efficiency and low toxicity 30 . However, Tian et al is the first study to carefully optimize unmodified PVam, and compare it with PEI in an in vivo context 27 .…”
Section: Recent Progress and Developmentmentioning
Ribonucleic acid (RNA) has emerged as one of the most promising therapeutic payloads in the field of gene therapy. There are many unique types of RNA that allow for a range of applications including vaccination, protein replacement therapy, autoimmune disease treatment, gene knockdown and gene editing. However, RNA triggers the host immune system, is vulnerable to degradation and has a low proclivity to enter cells spontaneously. Therefore, a delivery vehicle is required to facilitate the protection and uptake of RNA therapeutics into the desired host cells. Lipid nanoparticles have emerged as one of the only clinically approved vehicles for genetic payloads, including in the COVID‐19 messenger RNA vaccines. While lipid nanoparticles have distinct advantages, they also have drawbacks, including strong immune stimulation, complex manufacturing and formulation heterogeneity. In contrast, synthetic polymers are a widely studied group of gene delivery vehicles and boast distinct advantages, including biocompatibility, tunability, inexpensiveness, simple formulation and ease of modification. Some classes of polymers enhance efficient transfection efficiency, and lead to lower stimulation of the host immune system, making them more viable candidates for non‐vaccine‐related applications of RNA medicines. This review aims to identify the most promising classes of synthetic polymers, summarize recent research aimed at moving them into the clinic and postulate the future steps required for unlocking their full potential.
“…To improve the transfection efficiency of the amine-modified PVA polymers, some approaches were taken, such as the simultaneous administration of chloroquine (Oster et al, 2004), grafting of poly(lactic-co-glycolic acid) (PLGA) chains onto the DEAPA-PVA backbone [DEAPA-PVA-g-PLGA polymer consisting of a PVA (MW 15,000 g/mol) grafted onto PLGA with activation by DEAPA as an amine function] (Nguyen et al, 2008;Oster et al, 2006), or by increasing the (Dréan et al, 2018) amine density (Unger et al, 2007). In the study by Unger and co-workers (Unger et al, 2007), the authors showed that the degradation of DEAPA-PVA-g-PLGA copolymers depended on the degree and type of amine substitution and varied from <5 days to more than 4 weeks.…”
Nucleic acid‐based therapies have changed the paradigm of cancer treatment, where conventional treatment modalities still have several limitations in terms of efficacy and severe side effects. However, these biomolecules have a short half‐life in vivo, requiring multiple administrations, resulting in severe suffering, discomfort, and poor patient compliance. In the early days of (nano)biotechnology, these problems caused concern in the medical community, but recently it has been recognized that these challenges can be overcome by developing innovative formulations. This review focuses on the use of vinyl polymer‐based materials for the protection and delivery of nucleic acids in cancer. First, an overview of the properties of nucleic acids and their versatility as drugs is provided. Then, key information on the achievements to date, the most effective delivery methods, and the evaluation of functionalization approaches (stimulatory strategies) are critically discussed to highlight the importance of vinyl polymers in the new cancer treatment approaches.
This article is categorized under:
Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Biology‐Inspired Nanomaterials > Nucleic Acid‐Based Structures
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