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Self-assembled nucleolipids: from supramolecular structure to soft nucleic acid and drug delivery devices.

Allain V, Bourgaux C, Couvreur P - Nucleic Acids Res. (2011)

Bottom Line: This short review aims at presenting some recent illustrative examples of spontaneous nucleolipids self-assembly.Nucleolipids supramolecular assemblies are promising soft drug delivery systems, particularly for nucleic acids.Regarding prodrugs, squalenoylation is an innovative concept for improving efficacy and delivery of nucleosidic drugs.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire de Physicochimie, Pharmacotechnie et Biopharmacie, UMR CNRS 8612, Université Paris-Sud 11, Faculté de Pharmacie, 5 rue J.B. Clément, 92296 Châtenay-Malabry, France.

ABSTRACT
This short review aims at presenting some recent illustrative examples of spontaneous nucleolipids self-assembly. High-resolution structural investigations reveal the diversity and complexity of assemblies formed by these bioinspired amphiphiles, resulting from the interplay between aggregation of the lipid chains and base-base interactions. Nucleolipids supramolecular assemblies are promising soft drug delivery systems, particularly for nucleic acids. Regarding prodrugs, squalenoylation is an innovative concept for improving efficacy and delivery of nucleosidic drugs.

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Proposed model for the supramolecular structures formed by polyuridilic acid (polyU) mixed with dioctanoyl-phosphatidyl-uridine (diC8PA) in 0.05 M Tris buffer (pH 7.5). Clusters of polyU chains and diC8PA micelles formed first. After storage at 4°C for one week a well defined hexagonal phase was obtained, suggesting a hexagonal arrangement of diC8PA cylindrical micelles templated by strands of the complementary polynucleotide [reproduced with permission from Ref. (39)].
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gkr681-F5: Proposed model for the supramolecular structures formed by polyuridilic acid (polyU) mixed with dioctanoyl-phosphatidyl-uridine (diC8PA) in 0.05 M Tris buffer (pH 7.5). Clusters of polyU chains and diC8PA micelles formed first. After storage at 4°C for one week a well defined hexagonal phase was obtained, suggesting a hexagonal arrangement of diC8PA cylindrical micelles templated by strands of the complementary polynucleotide [reproduced with permission from Ref. (39)].

Mentions: Further, Baglioni and co-workers have provided the first proof of concept that complexes of nucleic acids and anionic nucleolipids can be stabilized via base pairing only, without the presence of cations (39,40). A polyuridilic acid chain (polyU) was chosen as model of a single strand of nucleotide homopolymer. This polynucleotide was shown to interact with either POPA or diC8PA, two negatively charged nucleolipids bearing the complementary adenine base. SAXS experiments have evidenced well-ordered POPA/polyU complexes. PolyU chains were intercalated between POPA fluid bilayers, inducing a lamellar spacing increase. They formed a 1D lattice, with a characteristic spacing depending on the POPA/polyU molar ratio. PolyU also bound to diC8PA spherical micelles, mediating the formation of clusters involving several polyU chains and micelles, as shown by dynamic light scattering, SANS and SAXS. Interestingly, these clusters showed a time-dependent evolution leading to the formation of a well-defined hexagonal phase with a lattice parameter of 98 Å. This supramolecular assembly could be modelled as a hexagonal array of diC8PA cylindrical micelles templated by single strands of the complementary polynucleotide (Figure 5). For both POPA/ polyU and diC8PA/polyU systems, the selective interactions between the complementary bases of the polynucleotide and the nucleolipids, confirmed by spectroscopic measurements, were the driving force for their supramolecular association. Thus, molecular recognition between complementary bases is able to overcome electrostatic repulsion between like-charged polynucleotide and nucleolipids and to trigger structural re-organization of the mixed system. Table 1 gathers nucleolipid/nucleic acid complex devices displaying transfection efficacy in vitro on various cell lines.Figure 5.


Self-assembled nucleolipids: from supramolecular structure to soft nucleic acid and drug delivery devices.

Allain V, Bourgaux C, Couvreur P - Nucleic Acids Res. (2011)

Proposed model for the supramolecular structures formed by polyuridilic acid (polyU) mixed with dioctanoyl-phosphatidyl-uridine (diC8PA) in 0.05 M Tris buffer (pH 7.5). Clusters of polyU chains and diC8PA micelles formed first. After storage at 4°C for one week a well defined hexagonal phase was obtained, suggesting a hexagonal arrangement of diC8PA cylindrical micelles templated by strands of the complementary polynucleotide [reproduced with permission from Ref. (39)].
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3300006&req=5

gkr681-F5: Proposed model for the supramolecular structures formed by polyuridilic acid (polyU) mixed with dioctanoyl-phosphatidyl-uridine (diC8PA) in 0.05 M Tris buffer (pH 7.5). Clusters of polyU chains and diC8PA micelles formed first. After storage at 4°C for one week a well defined hexagonal phase was obtained, suggesting a hexagonal arrangement of diC8PA cylindrical micelles templated by strands of the complementary polynucleotide [reproduced with permission from Ref. (39)].
Mentions: Further, Baglioni and co-workers have provided the first proof of concept that complexes of nucleic acids and anionic nucleolipids can be stabilized via base pairing only, without the presence of cations (39,40). A polyuridilic acid chain (polyU) was chosen as model of a single strand of nucleotide homopolymer. This polynucleotide was shown to interact with either POPA or diC8PA, two negatively charged nucleolipids bearing the complementary adenine base. SAXS experiments have evidenced well-ordered POPA/polyU complexes. PolyU chains were intercalated between POPA fluid bilayers, inducing a lamellar spacing increase. They formed a 1D lattice, with a characteristic spacing depending on the POPA/polyU molar ratio. PolyU also bound to diC8PA spherical micelles, mediating the formation of clusters involving several polyU chains and micelles, as shown by dynamic light scattering, SANS and SAXS. Interestingly, these clusters showed a time-dependent evolution leading to the formation of a well-defined hexagonal phase with a lattice parameter of 98 Å. This supramolecular assembly could be modelled as a hexagonal array of diC8PA cylindrical micelles templated by single strands of the complementary polynucleotide (Figure 5). For both POPA/ polyU and diC8PA/polyU systems, the selective interactions between the complementary bases of the polynucleotide and the nucleolipids, confirmed by spectroscopic measurements, were the driving force for their supramolecular association. Thus, molecular recognition between complementary bases is able to overcome electrostatic repulsion between like-charged polynucleotide and nucleolipids and to trigger structural re-organization of the mixed system. Table 1 gathers nucleolipid/nucleic acid complex devices displaying transfection efficacy in vitro on various cell lines.Figure 5.

Bottom Line: This short review aims at presenting some recent illustrative examples of spontaneous nucleolipids self-assembly.Nucleolipids supramolecular assemblies are promising soft drug delivery systems, particularly for nucleic acids.Regarding prodrugs, squalenoylation is an innovative concept for improving efficacy and delivery of nucleosidic drugs.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire de Physicochimie, Pharmacotechnie et Biopharmacie, UMR CNRS 8612, Université Paris-Sud 11, Faculté de Pharmacie, 5 rue J.B. Clément, 92296 Châtenay-Malabry, France.

ABSTRACT
This short review aims at presenting some recent illustrative examples of spontaneous nucleolipids self-assembly. High-resolution structural investigations reveal the diversity and complexity of assemblies formed by these bioinspired amphiphiles, resulting from the interplay between aggregation of the lipid chains and base-base interactions. Nucleolipids supramolecular assemblies are promising soft drug delivery systems, particularly for nucleic acids. Regarding prodrugs, squalenoylation is an innovative concept for improving efficacy and delivery of nucleosidic drugs.

Show MeSH