Dataset Information

Self-Assembly Mechanism of a Peptide-Based Drug Delivery Vehicle.

ABSTRACT: We report the mechanism of the concentration-dependent self-assembly of a tetrapeptide. Peptide Boc-Trp-Leu-Trp-Leu-OMe self-assembles to form discrete nanospheres at a low concentration. Tryptophan side chains point outwards of the nanospheres while leucine side chains point towards the core of the nanospheres. The nanospheres fuse together to become microspheres with the increase in the peptide concentration. At higher concentrations of the peptide, the microspheres start clustering. This is stabilized by the aromatic interactions between the side chains of the tryptophan residues that cover the outer surface of the peptide microspheres. In addition to behaving like the conventional hollow sphere-based drug delivery vehicles which entraps the drug and performs stimuli-responsive release, this prototype can interact, stabilize, and intercalate hydrophobic dye carboxyfluorescein and anti-cancer drug curcumin even on the surface through aromatic interactions. The dye/drug can be released in acidic pH and in the presence of physiologically relevant ions such as potassium.

SUBMITTER: Pandit G

PROVIDER: S-EPMC6045401 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Self-Assembly Mechanism of a Peptide-Based Drug Delivery Vehicle.

Pandit Gopal G Roy Karabi K Agarwal Umang U Chatterjee Sunanda S

ACS omega 20180315 3

We report the mechanism of the concentration-dependent self-assembly of a tetrapeptide. Peptide Boc-Trp-Leu-Trp-Leu-OMe self-assembles to form discrete nanospheres at a low concentration. Tryptophan side chains point outwards of the nanospheres while leucine side chains point towards the core of the nanospheres. The nanospheres fuse together to become microspheres with the increase in the peptide concentration. At higher concentrations of the peptide, the microspheres start clustering. This is s ...[more]

PMID: 30023862

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Project description:MicroRNAs (miRNAs) are small non-coding RNAs with a known role as mediators of gene expression in crucial biological processes, which converts them into high potential contenders in the ongoing search for effective therapeutic strategies. However, extracellular RNAs are unstable and rapidly degraded, reducing the possibility of successfully exerting a biological function in distant target cells. Strategies aimed at enhancing the therapeutic potential of miRNAs include the development of efficient, tissue-specific and nonimmunogenic delivery methods. Since miRNAs were discovered to be naturally transported within exosomes, a type of extracellular vesicle that confers protection against RNase degradation and increases miRNA stability have been proposed as ideal delivery vehicles for miRNA-based therapy. Although research in this field has grown rapidly in the last few years, a standard, reproducible and cost-effective protocol for exosome isolation and extracellular RNA delivery is lacking. We aimed to evaluate the use of milk-derived extracellular vesicles as vehicles for extracellular RNA drug delivery. With this purpose, exosomes were isolated from raw bovine milk, combining ultracentrifugation and size exclusion chromatography (SEC) methodology. Isolated exosomes were then loaded with exogenous hsa-miR148a-3p, a highly expressed miRNA in milk exosomes. The suitability of exosomes as delivery vehicles for extracellular RNAs was tested by evaluating the absorption of miR-148a-3p in hepatic (HepG2) and intestinal (Caco-2) cell lines. The potential exertion of a biological effect by miR-148a-3p was assessed by gene expression analysis, using microarrays. Results support that bovine milk is a cost-effective source of exosomes which can be used as nanocarriers of functional miRNAs with a potential use in RNA-based therapy. In addition, we show here that a combination of ultracentrifugation and SEC technics improve exosome enrichment, purity, and integrity for subsequent use.

Dataset Information

Self-Assembly Mechanism of a Peptide-Based Drug Delivery Vehicle.

Publications

Self-Assembly Mechanism of a Peptide-Based Drug Delivery Vehicle.

Similar Datasets

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