Dataset Information

Self-assembled nanoparticles based on modified cationic dipeptides and DNA: novel systems for gene delivery.

ABSTRACT:

Background

Gene therapy is most effective when delivery is both efficient and safe. However, it has often proven difficult to find a balance between efficiency and safety in case of viral or polymeric vectors for gene therapy. Peptide based delivery systems may be attractive alternatives but their relative instability to proteolysis is a major concern in realizing their potential application in biomedical sciences. In this work we report gene delivery potential of nanoparticles (Nps) synthesized from cationic dipeptides containing a non-protein amino acid α, β-dehydrophenylalanine (∆Phe) residue.

Methods

Dipeptides were synthesized using solution phase peptide synthesis method. Nps were formed using self-assembly. Nps were characterized using light scattering, electron microscopy. Transfection efficiency was tested in hepatocellular carcinoma (HuH 7) cells.

Results

The cationic dipeptides condensed plasmid DNA into discrete vesicular nanostructures. Dipeptide Nps are non-cytotoxic, protected the condensed DNAs from enzymatic degradation and ferried them successfully inside different types of cells. GFP encoding plasmid DNA loaded dipeptide Nps showed positive transfection and gene expression in HuH 7 cells.

Conclusions

The cationic dipeptide Nps can successfully deliver DNA without exerting any cytotoxic effect. Owing to their simple dipeptide origin, ease of synthesis, enhanced enzymatic stability as well unmatched biocompatibility, these could be successfully developed as vehicles for effective gene therapy.

SUBMITTER: Panda JJ

PROVIDER: S-EPMC3707807 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Publications

Self-assembled nanoparticles based on modified cationic dipeptides and DNA: novel systems for gene delivery.

Panda Jiban J JJ Varshney Aditi A Chauhan Virander S VS

Journal of nanobiotechnology 20130621

<h4>Background</h4>Gene therapy is most effective when delivery is both efficient and safe. However, it has often proven difficult to find a balance between efficiency and safety in case of viral or polymeric vectors for gene therapy. Peptide based delivery systems may be attractive alternatives but their relative instability to proteolysis is a major concern in realizing their potential application in biomedical sciences. In this work we report gene delivery potential of nanoparticles (Nps) syn ...[more]

PMID: 23800286

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Project description:The overuse of antibiotics exacerbates the development of antibiotic-resistant bacteria, threatening global public health, while most traditional antibiotics act on specific targets and sterilize through chemical modes. Therefore, it is a desperate need to design novel therapeutics or extraordinary strategies to overcome resistant bacteria. Herein, we report a positively charged nanocomposite PNs-Cur with a hydrodynamic diameter of 289.6 nm, which was fabricated by ring-opening polymerization of ε-caprolactone and Z-Lys-N-carboxyanhydrides (NCAs), and then natural curcumin was loaded onto the PCL core of PNs with a nanostructure through self-assembly, identified through UV-vis, and characterized by scanning electron microscopy (SEM) and dynamic light scattering (DLS). Especially, the self-assembly dynamics of PNs was simulated through molecular modeling to confirm the formation of a core-shell nanostructure. Biological assays revealed that PNs-Cur possessed broad-spectrum and efficient antibacterial activities against both Gram-positive and Gram-negative bacteria, including drug-resistant clinical bacteria and fungus, with MIC values in the range of 8-32 μg/mL. Also, in vivo evaluation showed that PNs-Cur exhibited strong antibacterial activities in infected mice. Importantly, the nanocomposite did not indeed induce the emergence of drug-resistant bacterial strains even after 21 passages, especially showing low toxicity regardless of in vivo or in vitro. The study of the antibacterial mechanism indicated that PNs-Cur could indeed destruct membrane potential, change the membrane potential, and cause the leakage of the cytoplasm. Concurrently, the released curcumin further plays a bactericidal role, eventually leading to bacterial irreversible apoptosis. This unique bacterial mode that PNs-Cur possesses may be the reason why it is not easy to make the bacteria susceptible to easily produce drug resistance. Overall, the constructed PNs-Cur is a promising antibacterial material, which provides a novel strategy to develop efficient antibacterial materials and combat increasingly prevalent bacterial infections.

Dataset Information

Self-assembled nanoparticles based on modified cationic dipeptides and DNA: novel systems for gene delivery.

Background

Methods

Results

Conclusions

Publications

Self-assembled nanoparticles based on modified cationic dipeptides and DNA: novel systems for gene delivery.

Similar Datasets

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