De Novo Design of Bioactive Protein-Resembling Nanospheres via Dendrimer-Templated Peptide Amphiphile Assembly

Lin, Bingyi; Marullo, Rachel; Robb, Maxwell J.; Krogstad, Daniel V.; Antoni, Per; Hawker, Craig J.; Campos, Luis M.; Tirrell, Matthew

doi:10.1021/nl202220q

Cited by 46 publications

(32 citation statements)

References 28 publications

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“…Peptides modified with hydrophobic, lipid-like tails known as ‘peptide amphiphiles’ (PAs) can be used as building blocks for the production of self-assembled nanostructures [6] or as functional coatings on preformed nanostructures [7], [8]. The physicochemical properties of the hydrophobic tails and the interactions between peptide headgroups specify the supramolecular geometry [9].…”

Section: Introductionmentioning

confidence: 99%

The Non-Peptidic Part Determines the Internalization Mechanism and Intracellular Trafficking of Peptide Amphiphiles

et al. 2013

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BackgroundPeptide amphiphiles (PAs) are a class of amphiphilic molecules able to self-assemble into nanomaterials that have shown efficient in vivo targeted delivery. Understanding the interactions of PAs with cells and the mechanisms of their internalization and intracellular trafficking is critical in their further development for therapeutic delivery applications.Methodology/Principal FindingsPAs of a novel, cell- and tissue-penetrating peptide were synthesized possessing two different lipophilic tail architectures and their interactions with prostate cancer cells were studied in vitro. Cell uptake of peptides was greatly enhanced post-modification. Internalization occurred via lipid-raft mediated endocytosis and was common for the two analogs studied. On the contrary, we identified the non-peptidic part as the determining factor of differences between intracellular trafficking and retention of PAs. PAs composed of di-stearyl lipid tails linked through poly(ethylene glycol) to the peptide exhibited higher exocytosis rates and employed different recycling pathways compared to ones consisting of di-palmitic-coupled peptides. As a result, cell association of the former PAs decreased with time.Conclusions/SignificanceControl over peptide intracellular localization and retention is possible by appropriate modification with synthetic hydrophobic tails. We propose this as a strategy to design improved peptide-based delivery systems.

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Section: Introductionmentioning

confidence: 99%

The Non-Peptidic Part Determines the Internalization Mechanism and Intracellular Trafficking of Peptide Amphiphiles

et al. 2013

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“…The PA building blocks arrange in well-defined and reproducible structures such as micelles, bilayers, vesicles, spheres or cylinders with the peptides oriented in an organized and functional way. Their applications range from diagnostic tools [19] over therapeutic approaches [20,21], drug delivery systems [22] to functional biomaterials [23]. With this molecular set-up the penetration through cell membranes is much better and the accessibility of the peptides to receptors enhanced.…”

Section: Introductionmentioning

confidence: 99%

Self-assembled peptide amphiphiles function as multivalent binder with increased hemagglutinin affinity

et al. 2013

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BackgroundA promising way in diagnostic and therapeutic applications is the development of peptide amphiphiles (PAs). Peptides with a palmitic acid alkylchain were designed and characterized to study the effect of the structure modifications on self-assembling capabilities and the multiple binding capacity to hemagglutinin (HA), the surface protein of influenza virus type A. The peptide amphiphiles consists of a hydrophilic headgroup with a biological functionality of the peptide sequence and a chemically conjugated hydrophobic tail. In solution they self-assemble easily to micelles with a hydrophobic core surrounded by a closely packed peptide-shell.ResultsIn this study the effect of a multiple peptide binding partner to the receptor binding site of HA could be determined with surface plasmon resonance measurements. The applied modification of the peptides causes signal amplification in relationship to the unmodified peptide wherein the high constant specificity persists. The molecular assembly of the peptides was characterized by the determination of critical micelle concentration (CMC) with concentration of 10-5 M and the colloidal size distribution.ConclusionThe modification of the physico-chemical parameters by producing peptide amphiphiles form monomeric structures which enhances the binding affinity and allows a better examination of the interaction with the virus surface protein hemagglutinin.

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“…Nature has devised numerous strategies to engineer precise architectures of biomacromolecules which are often integrated with one another to form the basis of intricate biological functions . Many synthetic systems have been developed that take inspiration from natures outstanding self‐assembly abilities, including phospholipids, peptide amphiphiles and more recently amphiphilic and ionic block copolymers (BCPs) . BCPs serve as versatile building blocks to fabricate a range of self‐assembled structures, such as micelles, structured microparticles, nanostructured particles, cross‐linked particles, and multivesicular particles .…”

Section: Introductionmentioning

confidence: 99%

Preparation of non‐spherical particles from amphiphilic block copolymers

Kempe

Wylie

Dimitriou

et al. 2015

J. Polym. Sci. Part A: Polym. Chem.

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Simple self‐assembly techniques to fabricate non‐spherical polymer particles, where surface composition and shape can be tuned through temperature and the choice of non‐solvents was developed. A series of amphiphilic polystyrene‐b‐poly(2‐ethyl‐2‐oxazoline) block copolymers were prepared and through solvent exchange techniques using varying non‐solvent composition a range of non‐spherical particles were formed. Faceted phase separated particles approximately 300 nm in diameter were obtained when self‐assembled from tetrahydrofuran (THF) into water compared with unique large multivesicular particles of 1200 nm size being obtained when assembled from THF into ethanol (EtOH). A range of intermediate structures were also prepared from a three part solvent system THF/water/EtOH. These techniques present new tools to engineer the self‐assembly of non‐spherical polymer particles. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 750–757

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De Novo Design of Bioactive Protein-Resembling Nanospheres via Dendrimer-Templated Peptide Amphiphile Assembly

Cited by 46 publications

References 28 publications

The Non-Peptidic Part Determines the Internalization Mechanism and Intracellular Trafficking of Peptide Amphiphiles

The Non-Peptidic Part Determines the Internalization Mechanism and Intracellular Trafficking of Peptide Amphiphiles

Self-assembled peptide amphiphiles function as multivalent binder with increased hemagglutinin affinity

Preparation of non‐spherical particles from amphiphilic block copolymers

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