Biodegradable PEG–dendritic block copolymers: synthesis and biofunctionality assessment as vectors of siRNA

Leiro, Victoria; Garcia, João P.; Moreno, Pedro M. D.; Spencer, Ana Patrícia; Fernandez‐Villamarin, Marcos; Riguera, Ricardo; Fernández-Megía, Eduardo; Pêgo, Ana Paula

doi:10.1039/c7tb00279c

Cited by 16 publications

(10 citation statements)

References 64 publications

(88 reference statements)

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“…On the other hand, it has been proven that the β-amino esters formed by Michael addition could undergo hydrolysis or enzymatic cleavage in the cytoplasm. This biodegradable behavior endows such materials with excellent DNA release capacity and good biocompatibility [31,32,33,34,35].…”

Section: Introductionmentioning

confidence: 99%

Biodegradable Gene Carriers Containing Rigid Aromatic Linkage with Enhanced DNA Binding and Cell Uptake

et al. 2018

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The linking and modification of low molecular weight cationic polymers (oligomers) has become an attracted strategy to construct non-viral gene carriers with good transfection efficiency and much reduced cytotoxicity. In this study, PEI 600 Da was linked by biodegradable bridges containing rigid aromatic rings. The introduction of aromatic rings enhanced the DNA-binding ability of the target polymers and also improved the stability of the formed polymer/DNA complexes. The biodegradable property and resulted DNA release were verified by enzyme stimulated gel electrophoresis experiment. These materials have lower molecular weights compared to PEI 25 kDa, but exhibited higher transfection efficiency, especially in the presence of serum. Flow cytometry and confocal laser scanning microscopy results indicate that the polymers with aromatic rings could induce higher cellular uptake. This strategy for the construction of non-viral gene vectors may be applied as an efficient and promising method for gene delivery.

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Section: Introductionmentioning

confidence: 99%

Biodegradable Gene Carriers Containing Rigid Aromatic Linkage with Enhanced DNA Binding and Cell Uptake

et al. 2018

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“…On the other hand, the convergent synthesis is initiated on the perfect branched dendrons (dendrimer wedges), which are then linked to a multifunctional core after the activation/deprotection of their focal point [77]. As a result, the great number of functional groups in the periphery of dendrimers (like thiols, amines, hydroxyl, carboxylic acids and azide groups, among others) allows for the tethering of different bioactive ligands in a specific and controllable manner according to the desired properties and applications, mimicking the multivalency present in several biological systems [78].…”

Section: Dendrimer-based Nanosystemsmentioning

confidence: 99%

“…Therefore, the use of biocompatible and biodegradable materials could be an answer to avoid safety concerns and exacerbated bioaccumulation, and many groups are now focused in the development of this type of carriers. Recently, we reported a new family of biodegradable PEG-GATGE (gallic acid triethylene glycol ester) dendritic block copolymers, as well as their function as siRNA vectors, which showed an adequate degradation rate [78]. Additionally, these dendritic structures allow an easy and versatile functionalization by 'click' chemistry, opening a broad range of functionalization possibilities for these vectors.…”

Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

Breaking Barriers: Bioinspired Strategies for Targeted Neuronal Delivery to the Central Nervous System

et al. 2020

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Central nervous system (CNS) disorders encompass a vast spectrum of pathological conditions and represent a growing concern worldwide. Despite the high social and clinical interest in trying to solve these pathologies, there are many challenges to bridge in order to achieve an effective therapy. One of the main obstacles to advancements in this field that has hampered many of the therapeutic strategies proposed to date is the presence of the CNS barriers that restrict the access to the brain. However, adequate brain biodistribution and neuronal cells specific accumulation in the targeted site also represent major hurdles to the attainment of a successful CNS treatment. Over the last few years, nanotechnology has taken a step forward towards the development of therapeutics in neurologic diseases and different approaches have been developed to surpass these obstacles. The versatility of the designed nanocarriers in terms of physical and chemical properties, and the possibility to functionalize them with specific moieties, have resulted in improved neurotargeted delivery profiles. With the concomitant progress in biology research, many of these strategies have been inspired by nature and have taken advantage of physiological processes to achieve brain delivery. Here, the different nanosystems and targeting moieties used to achieve a neuronal delivery reported in the open literature are comprehensively reviewed and critically discussed, with emphasis on the most recent bioinspired advances in the field. Finally, we express our view on the paramount challenges in targeted neuronal delivery that need to be overcome for these promising therapeutics to move from the bench to the bedside.

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“…Therefore, the ideal delivery vehicle should be biodegradable to prevent bioaccumulation and subsequent cytotoxicity [86,[124][125][126]. Moreover, the dendrimers' biodegradability can also contribute to the efficient release of the transported NA [125,127], and consequently yield higher RNAi.…”

Section: A01/00mentioning

confidence: 99%

Delivering siRNA with Dendrimers: In Vivo Applications

Leiro

Santos

Pêgo

2017

CGT

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Over the last decades, gene therapy has emerged as a pioneering therapeutic approach to treat or prevent several diseases. Among the explored strategies, the short-term silencing of protein coding genes mediated by siRNAs has a good therapeutic potential in a clinical setting. However, the widespread use of siRNA will require the development of clinically suitable, safe and effective vehicles with the ability to complex and deliver siRNA into target cells with minimal toxicity. Lately, dendrimers have gained considerable attention as non-viral vectors in nucleic acid delivery due to their unique structural characteristics (globular, well defined and highly branched structure, multivalency, low polydispersity and tunable nanosize), along with their relevant capacity to complex and protect nucleic acids in compact nanostructures, which can be functionalized with targeting moieties in order to get cell specificity. Here, we present an overview of the state-of-the-art of the most significant and recent advances on the use of dendrimers as siRNA delivery vectors, with particular focus on the in vivo applications. We will cover the use of different dendrimers, distinct administration routes, toxicity issues, as well as the target tissue or disease, highlighting the potential of dendrimers as nanocarriers for therapeutic and biomedical applications.

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Biodegradable PEG–dendritic block copolymers: synthesis and biofunctionality assessment as vectors of siRNA

Abstract: New hybrid-biodegradable PEG–dendritic block copolymers as versatile delivery vectors for biomedical applications. Here, their biofunctionality as siRNA vectors is presented.

Cited by 16 publications

References 64 publications

Biodegradable Gene Carriers Containing Rigid Aromatic Linkage with Enhanced DNA Binding and Cell Uptake

Biodegradable Gene Carriers Containing Rigid Aromatic Linkage with Enhanced DNA Binding and Cell Uptake

Breaking Barriers: Bioinspired Strategies for Targeted Neuronal Delivery to the Central Nervous System

Delivering siRNA with Dendrimers: In Vivo Applications

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