Self-assembling asymmetric peptide-dendrimer micelles – a platform for effective and versatile in vitro nucleic acid delivery

Kokil, Ganesh R.; Veedu, Rakesh N.; Le, Bao T.; Ramm, Grant A.; Parekh, Harendra S.

doi:10.1038/s41598-018-22902-9

Cited by 24 publications

(12 citation statements)

References 36 publications

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“…Notably, formation of cationic micellar nanoassemblies increases the local positive charge density in solution, supporting an effective DNA condensation [38]. For example, cationic peptide dendrimers with side arm lipid conjugates that were able to selfassemble into micelles and condense siRNA, were introduced as a versatile platform for effective nucleic acid delivery [39]. The peptide-based micelles were non-cytotoxic at various concentrations The main driving force for the self-assembly are non-covalent interactions like hydrophobic and ionic interactions, van der Waals forces, hydrogen bonds, and π-π stacking [29].…”

Section: Micellesmentioning

confidence: 98%

Peptide-Based Nanoassemblies in Gene Therapy and Diagnosis: Paving the Way for Clinical Application

et al. 2020

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Nanotechnology approaches play an important role in developing novel and efficient carriers for biomedical applications. Peptides are particularly appealing to generate such nanocarriers because they can be rationally designed to serve as building blocks for self-assembling nanoscale structures with great potential as therapeutic or diagnostic delivery vehicles. In this review, we describe peptide-based nanoassemblies and highlight features that make them particularly attractive for the delivery of nucleic acids to host cells or improve the specificity and sensitivity of probes in diagnostic imaging. We outline the current state in the design of peptides and peptide-conjugates and the paradigms of their self-assembly into well-defined nanostructures, as well as the co-assembly of nucleic acids to form less structured nanoparticles. Various recent examples of engineered peptides and peptide-conjugates promoting self-assembly and providing the structures with wanted functionalities are presented. The advantages of peptides are not only their biocompatibility and biodegradability, but the possibility of sheer limitless combinations and modifications of amino acid residues to induce the assembly of modular, multiplexed delivery systems. Moreover, functions that nature encoded in peptides, such as their ability to target molecular recognition sites, can be emulated repeatedly in nanoassemblies. Finally, we present recent examples where self-assembled peptide-based assemblies with “smart” activity are used in vivo. Gene delivery and diagnostic imaging in mouse tumor models exemplify the great potential of peptide nanoassemblies for future clinical applications.

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Section: Micellesmentioning

confidence: 98%

Peptide-Based Nanoassemblies in Gene Therapy and Diagnosis: Paving the Way for Clinical Application

et al. 2020

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“…These polymer structures have evolved alongside the progression of peptide synthesis chemistry to create multibranched dendritic structures and/or components thereof which can be easily synthesised via techniques such as SPPS [192] and either built from the core out or pieced together via simple chemical manipulation such as that of "click chemistry" [193] and other bioconjugation techniques [102], previously described. The structures which are built in a step-wise manner where the structure is built from the core outwards adding each layer has been termed "divergent" and the ligation of several segments brought together onto a central core and built inwards termed "convergent" [194].…”

Section: Peptide-based Polymers: Dendrimer Systemsmentioning

confidence: 99%

Peptide Multimerization as Leads for Therapeutic Development

Sheard

O'Brien-Simpson

et al. 2021

Biologics

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Multimerization of peptide structures has been a logical evolution in their development as potential therapeutic molecules. The multivalent properties of these assemblies have attracted much attention from researchers in the past and the development of more complex branching dendrimeric structures, with a wide array of biocompatible building blocks is revealing previously unseen properties and activities. These branching multimer and dendrimer structures can induce greater effect on cellular targets than monomeric forms and act as potent antimicrobials, potential vaccine alternatives and promising candidates in biomedical imaging and drug delivery applications. This review aims to outline the chemical synthetic innovations for the development of these highly complex structures and highlight the extensive capabilities of these molecules to rival those of natural biomolecules.

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“…Recently, lipidated peptide dendrimers for nucleic acid delivery have been reported. − In another report, polylysine dendrimers conjugated with multiple copies of arginine-rich cell-penetrating peptides were examined for their splice-redirecting efficiency in HeLa cells . Studies revealed that 2- and 4-branched dendritic conjugates significantly transfect HeLa cells with charge-neutral peptide nucleic acid 750(PNA) in the presence of serum.…”

Section: An Overview Of Peptide Dendrimersmentioning

confidence: 99%

Designer Peptide and Protein Dendrimers: A Cross-Sectional Analysis

et al. 2019

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Dendrimers have attracted immense interest in science and technology due to their unique chemical structure that offers a myriad of opportunities for researchers. Dendritic design allows us to present peptides in a branched three-dimensional fashion that eventually leads to a globular shape, thus mimicking globular proteins. Peptide dendrimers, unlike other classes of dendrimers, have immense applications in biomedical research due to their biological origin. The diversity of potential building blocks and innumerable possibilities for design, along with the fact that the area is relatively underexplored, make peptide dendrimers sought-after candidates for various applications. This review summarizes the stepwise evolution of peptidic dendrimers along with their multifaceted applications in various fields. Further, the introduction of biomacromolecules such as proteins to a dendritic scaffold, resulting in complex macromolecules with discrete molecular weights, is an altogether new addition to the area of organic chemistry. The synthesis of highly complex and fully folded biomacromolecules on a dendritic scaffold requires expertise in synthetic organic chemistry and biology. Presently, there are only a handful of examples of protein dendrimers; we believe that these limited examples will fuel further research in this area.

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Self-assembling asymmetric peptide-dendrimer micelles – a platform for effective and versatile in vitro nucleic acid delivery

Cited by 24 publications

References 36 publications

Peptide-Based Nanoassemblies in Gene Therapy and Diagnosis: Paving the Way for Clinical Application

Peptide-Based Nanoassemblies in Gene Therapy and Diagnosis: Paving the Way for Clinical Application

Peptide Multimerization as Leads for Therapeutic Development

Designer Peptide and Protein Dendrimers: A Cross-Sectional Analysis

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