Abstract：
:To achieve enhanced gene transfection efficiency with ocular eye-drop therapy, a cationic core-shell liponanoparticle (DLCS-NP) was designed by enveloping the plasmid-laden chitosan nanoparticle (CS-NP) into a cationic lipid shell. The cellular uptake of DLCS-NP was up to 1.25-fold and 5-fold higher than that of CS-NP and lipid-coated chitosan nanoparticles (LCS-NP), respectively. Further endocytosis inhibition investigation discovered that facilitated by the cationic outer lipid layer, several other distinct pathways (besides clathrin-mediated endocytosis) were involved in the endocytosis of DLCS-NP. Endolysosome trafficking experiment verified that cationic lipid coating could facilitate the endolysosome escape of DLCS-NP. Consequently, using enhanced green fluorescence protein (EGFP) as a reporter gene, DLCS-NP-treated human conjunctival epithelial cells exhibited 3.1- and 3.5-fold more intense EGFP expression than that of LCS-NP and CS-NP, respectively. Finally, in vivo transfection experiments on rabbits revealed that EGFP expression exhibited 2.52-fold increase in DLCS-NP group than that of CS-NP group. In summary, this type of cationic core-shell liponanoparticle, possessing multiple functions including better DNA protecting effect, superior cellular uptake efficiency, utilization of multiple endocytic pathways, and endolysosome escaping ability, may represent a promising strategy for ocular gene delivery.
journal_name
Biomaterialsjournal_title
Biomaterialsauthors
Jiang M,Gan L,Zhu C,Dong Y,Liu J,Gan Ydoi
10.1016/j.biomaterials.2012.06.079subject
Has Abstractpub_date
2012-10-01 00:00:00pages
7621-30issue
30eissn
0142-9612issn
1878-5905pii
S0142-9612(12)00729-6journal_volume
33pub_type
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