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Effect of inserted spacer in hepatic cell-penetrating multifunctional peptide component on the DNA intracellular delivery of quaternary complexes based on modular design.

ABSTRACT: A safe and efficient quaternary gene delivery system (named Q-complexes) was constructed based on self-assembly of molecules through noncovalent bonds. This system was formulated through the cooperation and competing interactions of cationic liposomes, multifunctional peptides, and DNA, followed by coating hyaluronic acid on the surface of the ternary complexes. The multifunctional peptide was composed of two functional domains: penetrating hepatic tumor-targeted cell moiety (KRPTMRFRYTWNPMK) and a wrapping gene sequence (polyarginine 16). The effect of spacer insertion between the two domains of multifunctional peptide on the intracellular transfection of Q-complexes was further studied. Experimental results showed that the formulations assembled with various peptides in the spacer elements possessed different intercellular pathways and transfection efficiencies. The Q-complexes containing peptide in the absence of spacer element (Pa) showed the highest gene expression among all samples. The Q-complexes containing peptides with a noncleavable spacer GA (Pc) had no ability of intracellular nucleic acid delivery, whereas those with a cleavable spacer RVRR (Pd) showed moderate transfection activity. These results demonstrated that the different spacers inserted in the multifunctional peptide played an important role in in vitro DNA transfection efficiency. Atomic force microscopy images showed that the morphologies of ternary complexes (LPcD) and Q-complexes (HLcPD) were crystal lamellas, whereas those of other nanocomplexes were spheres. Circular dichroism showed the changed configuration of peptide with spacer GA in nanocomplexes compared with that of its free state, whereas the Pa configuration without spacer in nanocomplexes was consistent with that of its free state. The present study contributed to the structural understanding of Q-complexes, and further effective modification is in progress.

SUBMITTER: Zhang L

PROVIDER: S-EPMC5126006 | biostudies-other | 2016

REPOSITORIES: biostudies-other

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Effect of inserted spacer in hepatic cell-penetrating multifunctional peptide component on the DNA intracellular delivery of quaternary complexes based on modular design.

Zhang Luchen L Li Zhenbo Z Sun Fangli F Xu Yuhong Y Du Zixiu Z

International journal of nanomedicine 20161124

A safe and efficient quaternary gene delivery system (named Q-complexes) was constructed based on self-assembly of molecules through noncovalent bonds. This system was formulated through the cooperation and competing interactions of cationic liposomes, multifunctional peptides, and DNA, followed by coating hyaluronic acid on the surface of the ternary complexes. The multifunctional peptide was composed of two functional domains: penetrating hepatic tumor-targeted cell moiety (KRPTMRFRYTWNPMK) an ...[more]

PMID: 27920533

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Project description:Current methods of microtia reconstruction include carving an auricular framework from the costal synchondrosis. This requires considerable skill and may create a substantial defect at the donor site.To present a modular component assembly (MCA) approach that minimizes the procedural difficulty with microtia repair and reduces the amount of cartilage to a single rib.Ex vivo study and survey. A single porcine rib was sectioned into multiple slices using a cartilage guillotine, cut into components outlined by 3-dimensional printed templates, and assembled into an auricular scaffold. Electromechanical reshaping was used to bend cartilage slices for creation of the helical rim. Chondrocyte viability was confirmed using confocal imaging. Ten surgeons reviewed the scaffold constructed with the MCA approach to evaluate aesthetics, stability, and clinical feasibility. The study was conducted from June 5 to December 18, 2014.The primary outcome was creation of a modular component assembly method that decreases the total amount of rib needed for scaffold construction, as well as overall scaffold acceptability. The surgeons provided their assessments through a Likert-scale survey, with responses ranging from 1 (disagree with the statement) to 5 (agree with the statement). Thus, a higher score represents that the surgeon agrees that the scaffold is structurally and aesthetically acceptable and feasible.An auricular framework with projection and curvature was fashioned from 1 rib. The 10 surgeons who participated in the survey indicated that the MCA scaffold would meet minimal aesthetic and anatomic acceptability. When embedded under a covering, the region of the helix and antihelix of the scaffold scored significantly higher on the assessment survey than that of an embedded alloplast implant (mean [SD], 4.6 [0.97] vs 3.5 [1.27]; P?=?.007). Otherwise, no significant difference was found between the embedded MCA and alloplast implants (4.42 [0.48] vs 3.87 [0.41]; P?=?.13). Cartilage prepared with electromechanical reshaping was viable.This study demonstrates that 1 rib can be used to create an aesthetic and durable framework for microtia repair. Precise assembly and the ability to obtain thin, uniform slices of cartilage were essential. This cartilage-sparing MCA approach may be an alternative to classic techniques.NA.

Dataset Information

Effect of inserted spacer in hepatic cell-penetrating multifunctional peptide component on the DNA intracellular delivery of quaternary complexes based on modular design.

Publications

Effect of inserted spacer in hepatic cell-penetrating multifunctional peptide component on the DNA intracellular delivery of quaternary complexes based on modular design.

Similar Datasets

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