Stereoselective pH Responsive Peptide Dendrimers for siRNA Transfection.

  title={Stereoselective pH Responsive Peptide Dendrimers for siRNA Transfection.},
  author={Mark P. Heitz and Sacha Javor and Tamis Darbre and Jean‐Louis Reymond},
  journal={Bioconjugate chemistry},
Transfecting nucleic acids into cells is an essential procedure in biological research usually performed using nonviral transfection reagents. Unfortunately, most transfection reagents have polymeric or undisclosed structures and require nonstandard synthetic procedures. Herein we report peptide dendrimers accessible as pure products from standard building blocks by solid-phase peptide synthesis and acting as nontoxic single component siRNA transfection reagents for a variety of cell lines with… 

Fluorescent Peptide Dendrimers for siRNA Transfection: Tracking pH Responsive Aggregation, siRNA Binding and Cell Penetration.

Studies of peptide dendrimers as single component siRNA transfection reagents accessible in pure form by solid-phase peptide synthesis are extended by identifying analogs bearing a coumarin or BODIPY fluorescent label in their core and displaying comparable si RNA transfections efficiencies, pH dependent aggregation, siRNA binding and secondary structures.

Lipophilic Peptide Dendrimers for Delivery of Splice-Switching Oligonucleotides

The findings demonstrate the potential of lipid-conjugated, D-amino acid-containing peptide dendrimers to be utilized as an effective and safe delivery vector for splice-switching ONs.

Amphiphilic peptide dendrimer-based nanovehicles for safe and effective siRNA delivery

Novel amphiphilic peptide dendrimers that are able to self-assemble into supramolecular nanoassemblies that are capable of entrapping siRNA molecules into nanoparticles to protect siRNA from enzymatic degradation and promote efficient intracellular uptake without evident toxicity are disclosed.

Sugar and Polymer Excipients Enhance Uptake and Splice-Switching Activity of Peptide-Dendrimer/Lipid/Oligonucleotide Formulations

It is suggested that the highlighted impact of tested excipients would potentially assist in formulation development to deliver ON therapeutics in pre-clinical and clinical settings.

Intracellular Communication between Synthetic Macromolecules.

A library of dendronized bottlebrush polymers with controlled defects is developed, displaying a level of precision surpassed only by biological molecules like DNA, RNA, and proteins, challenging the assumption that delivery agents behave as bystanders that enable transfection by passive intracellular release of genetic cargo.

Amphiphilic Dendrimer Vectors for RNA Delivery: State-of-the-Art and Future Perspective.

This Account presents state-of-the-art amphiphilic dendrimers for nucleic acid delivery, which have pioneered lipid/dendrimer conjugates for siRNA delivery with the view to harnessing the delivery advantages of both lipid and polymer vectors while enjoying the unique structural features of d endrimers.

Phenylboronic Acid Modification Augments the Lysosome Escape and Antitumor Efficacy of a Cylindrical Polymer Brush-Based Prodrug.

This work provides a novel strategy for facilitating the lysosome escape of nanomaterials and demonstrates that PBA modification is an effective way to improve the overall properties of nanomedicines including the tumor therapeutic efficacy.

Smart Drug Delivery Systems



Peptide Dendrimer-Lipid Conjugates as DNA and siRNA Transfection Reagents: Role of Charge Distribution Across Generations.

This work has developed a new class of well-defined and easily modifiable transfection reagents in the form of peptide dendrimers which self-assemble with DNA or siRNA and lipofectin to form nanoparticles which efficiently enter mammalian cells and liberate their nucleic acid cargo.

Efficient Transfection of siRNA by Peptide Dendrimer–Lipid Conjugates

This work established peptide dendrimers as siRNA transfection reagents and recorded structure–activity relationships that highlighted the importance of positive charge distribution in the two outer layers and a hydrophobic core as key features for efficient performance.

Novel peptide‐dendrimer/lipid/oligonucleotide ternary complexes for efficient cellular uptake and improved splice‐switching activity

  • Osama SaherCristina S. J. Rocha C. Smith
  • Biology, Chemistry
    European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
  • 2018

Peptide Dendrimer/Lipid Hybrid Systems Are Efficient DNA Transfection Reagents: Structure–Activity Relationships Highlight the Role of Charge Distribution Across Dendrimer Generations

Emerging structure–activity relationships show that dendrimers with cationic and hydrophobic residues distributed in each generation are transfecting most efficiently, and the trigenerational dendritic structure has an advantage over a linear analogue worth up to an order of magnitude.

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

The delivery efficiency of asymmetric peptide dendrimers in H-4-II-E (rat hepatoma), H2K (mdx mouse myoblast), and DAOY (human medulloblastoma) cells demonstrated that cholic acid-conjugated asymmetric d endrimers possess far superior delivery efficiency when compared to the commercial standards, Lip ofectamine 2000 or Lipofectin®.

A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine.

Together, these properties make PEI a promising vector for gene therapy and an outstanding core for the design of more sophisticated devices because its efficiency relies on extensive lysosome buffering that protects DNA from nuclease degradation, and consequent lysOSomal swelling and rupture that provide an escape mechanism for the PEI/DNA particles.

Mastering Dendrimer Self-Assembly for Efficient siRNA Delivery: From Conceptual Design to In Vivo Efficient Gene Silencing.

It is demonstrated that, with the optimal balance of hydrophobicity and hydrophilicity, one of the self-assembled nanomicellar systems is able to deliver small interfering RNA and achieve effective gene silencing both in cells and in vivo, thus paving the way for future biomedical implementation.

Multivalent dendritic polyglycerolamine with arginine and histidine end groups for efficient siRNA transfection

This study indicates that AAdPGs containing higher degrees of His display lower cytotoxicity and more efficient endosomal escape in siRNA transfection.

Topical delivery of siRNA-based spherical nucleic acid nanoparticle conjugates for gene regulation

It is shown that spherical nucleic acid nanoparticle conjugates (SNA-NCs), gold cores surrounded by a dense shell of highly oriented, covalently immobilized siRNA, freely penetrate almost 100% of keratinocytes in vitro, mouse skin, and human epidermis within hours after application.

Adaptive amphiphilic dendrimer-based nanoassemblies as robust and versatile siRNA delivery systems.

It is reported for the first time that an amphiphilic dendrimer is able to self-assemble into adaptive supramolecular assemblies upon interaction with siRNA, and effectively delivers siRNAs to various cell lines, including human primary and stem cells, thereby outperforming the currently available nonviral vectors.