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Development of polymeric-cationic peptide composite nanoparticles, a nanoparticle-in-nanoparticle system for controlled gene delivery.

Jain AK, Massey A, Yusuf H, McDonald DM, McCarthy HO, Kett VL - Int J Nanomedicine (2015)

Bottom Line: The best formulation was selected and was able to transfect cells while maintaining viability.The effect of transferrin-appended composite nanoparticles was also studied.Thus, we have demonstrated the manufacture of composite nanoparticles for the controlled delivery of DNA.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Medical Biology Centre, Queen's University Belfast, Belfast, Northern Ireland, UK ; Weatherall Institute of Molecular Medicine, MRC Molecular Haematology Unit, University of Oxford, John Radcliffe Hospital, Oxford, UK.

ABSTRACT
We report the formulation of novel composite nanoparticles that combine the high transfection efficiency of cationic peptide-DNA nanoparticles with the biocompatibility and prolonged delivery of polylactic acid-polyethylene glycol (PLA-PEG). The cationic cell-penetrating peptide RALA was used to condense DNA into nanoparticles that were encapsulated within a range of PLA-PEG copolymers. The composite nanoparticles produced exhibited excellent physicochemical properties including size <200 nm and encapsulation efficiency >80%. Images of the composite nanoparticles obtained with a new transmission electron microscopy staining method revealed the peptide-DNA nanoparticles within the PLA-PEG matrix. Varying the copolymers modulated the DNA release rate >6 weeks in vitro. The best formulation was selected and was able to transfect cells while maintaining viability. The effect of transferrin-appended composite nanoparticles was also studied. Thus, we have demonstrated the manufacture of composite nanoparticles for the controlled delivery of DNA.

No MeSH data available.


Sequence and structure of RALA. Overview of composition of the composite nanoparticles.Notes: (A) Primary sequence (top), secondary structure (middle), and surface representations of the RALA peptide, bottom left shows rotation to reveal the hydrophobic side, bottom right shows rotation to reveal the hydrophilic side. (B) Schematic representation of polymeric–cationic peptide composite nanoparticles.Abbreviations: pDNA, plasmid DNA; PEG, polyethylene glycol; PLA, polylactic acid; RNPs, RALA nanoparticles.
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f1-ijn-10-7183: Sequence and structure of RALA. Overview of composition of the composite nanoparticles.Notes: (A) Primary sequence (top), secondary structure (middle), and surface representations of the RALA peptide, bottom left shows rotation to reveal the hydrophobic side, bottom right shows rotation to reveal the hydrophilic side. (B) Schematic representation of polymeric–cationic peptide composite nanoparticles.Abbreviations: pDNA, plasmid DNA; PEG, polyethylene glycol; PLA, polylactic acid; RNPs, RALA nanoparticles.

Mentions: In this paper, composite nanoparticles were developed to exploit the advantages of both cationic cell-penetrating peptides and PLA-PEG nanoparticles. Cell-penetrating peptides have emerged as a specialized tool for the efficient intracellular delivery of the therapeutic cargo.14 For gene delivery, cell-penetrating peptides that include positively charged amphiphilic peptides ≥30 amino acid in length15 exhibit enhanced cell compatibility when compared with other available options.16–18 The cationic cell-penetrating peptide RALA19 was chosen to condense the DNA and form the core of the nanoparticles for efficient transfection of the cells. RALA exhibits an alpha helical structure in a hydrophilic environment with hydrophobic amino acids on one face and hydrophilic on the other, making it a suitable candidate for DNA condensation and efficient membrane perturbation. The sequence and predicted secondary structure of the peptide were generated using PEPstr server,20 and the surface was generated using UCSF chimera (Version 1.9) software (Figure 1).21


Development of polymeric-cationic peptide composite nanoparticles, a nanoparticle-in-nanoparticle system for controlled gene delivery.

Jain AK, Massey A, Yusuf H, McDonald DM, McCarthy HO, Kett VL - Int J Nanomedicine (2015)

Sequence and structure of RALA. Overview of composition of the composite nanoparticles.Notes: (A) Primary sequence (top), secondary structure (middle), and surface representations of the RALA peptide, bottom left shows rotation to reveal the hydrophobic side, bottom right shows rotation to reveal the hydrophilic side. (B) Schematic representation of polymeric–cationic peptide composite nanoparticles.Abbreviations: pDNA, plasmid DNA; PEG, polyethylene glycol; PLA, polylactic acid; RNPs, RALA nanoparticles.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664533&req=5

f1-ijn-10-7183: Sequence and structure of RALA. Overview of composition of the composite nanoparticles.Notes: (A) Primary sequence (top), secondary structure (middle), and surface representations of the RALA peptide, bottom left shows rotation to reveal the hydrophobic side, bottom right shows rotation to reveal the hydrophilic side. (B) Schematic representation of polymeric–cationic peptide composite nanoparticles.Abbreviations: pDNA, plasmid DNA; PEG, polyethylene glycol; PLA, polylactic acid; RNPs, RALA nanoparticles.
Mentions: In this paper, composite nanoparticles were developed to exploit the advantages of both cationic cell-penetrating peptides and PLA-PEG nanoparticles. Cell-penetrating peptides have emerged as a specialized tool for the efficient intracellular delivery of the therapeutic cargo.14 For gene delivery, cell-penetrating peptides that include positively charged amphiphilic peptides ≥30 amino acid in length15 exhibit enhanced cell compatibility when compared with other available options.16–18 The cationic cell-penetrating peptide RALA19 was chosen to condense the DNA and form the core of the nanoparticles for efficient transfection of the cells. RALA exhibits an alpha helical structure in a hydrophilic environment with hydrophobic amino acids on one face and hydrophilic on the other, making it a suitable candidate for DNA condensation and efficient membrane perturbation. The sequence and predicted secondary structure of the peptide were generated using PEPstr server,20 and the surface was generated using UCSF chimera (Version 1.9) software (Figure 1).21

Bottom Line: The best formulation was selected and was able to transfect cells while maintaining viability.The effect of transferrin-appended composite nanoparticles was also studied.Thus, we have demonstrated the manufacture of composite nanoparticles for the controlled delivery of DNA.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Medical Biology Centre, Queen's University Belfast, Belfast, Northern Ireland, UK ; Weatherall Institute of Molecular Medicine, MRC Molecular Haematology Unit, University of Oxford, John Radcliffe Hospital, Oxford, UK.

ABSTRACT
We report the formulation of novel composite nanoparticles that combine the high transfection efficiency of cationic peptide-DNA nanoparticles with the biocompatibility and prolonged delivery of polylactic acid-polyethylene glycol (PLA-PEG). The cationic cell-penetrating peptide RALA was used to condense DNA into nanoparticles that were encapsulated within a range of PLA-PEG copolymers. The composite nanoparticles produced exhibited excellent physicochemical properties including size <200 nm and encapsulation efficiency >80%. Images of the composite nanoparticles obtained with a new transmission electron microscopy staining method revealed the peptide-DNA nanoparticles within the PLA-PEG matrix. Varying the copolymers modulated the DNA release rate >6 weeks in vitro. The best formulation was selected and was able to transfect cells while maintaining viability. The effect of transferrin-appended composite nanoparticles was also studied. Thus, we have demonstrated the manufacture of composite nanoparticles for the controlled delivery of DNA.

No MeSH data available.