Exploring the efficiency of gallic acid-based dendrimers and their block copolymers with PEG as gene carriers.
The synthesis of a new family of amino-functionalized gallic acid-triethylene glycol (GATG) dendrimers and their block copolymers with polyethylene glycol (PEG) has recently being disclosed. In addition, these dendrimers have shown potential for gene delivery applications, as they efficiently complex nucleic acids and form small and homogeneous dendriplexes. On this basis, the present study aimed to explore the interaction of the engineered dendriplexes with blood components, as well as their stability, cytotoxicity and ability to enter and transfect mammalian cells. Results show that GATG dendrimers can form stable dendriplexes, protect the associated pDNA from degradation, and are biocompatible with HEK-293T cells and erythrocytes. More importantly, dendriplexes are effectively internalized by HEK-293T cells, which are successfully transfected. Besides, PEGylation has a marked influence on the properties of the resulting dendriplexes. While PEGylated GATG dendrimers have improved biocompatibility, the long PEG chains limit their uptake by HEK-293T cells, and thus, their ability to transfect them. As a consequence, the degree of PEGylation in dendriplexes containing dendrimer/block copolymer mixtures emerges as an important parameter to be modulated in order to obtain an optimized stealth formulation able to effectively induce the expression of the encoded protein.
Department of Pharmacy & Pharmaceutical Technology, Center for Molecular Medicine & Chronic Diseases, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain. maria.fuente@usc.es
María
M
de la Fuente
Manuela
M
Raviña
Ana
A
Sousa-Herves
Juan
J
Correa
Ricardo
R
Riguera
Eduardo
E
Fernandez-Megia
Alejandro
A
Sánchez
María José
MJ
Alonso
D000818:Animals; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D050091:Dendrimers / Q000737:chemistry* / Q000378:metabolism; D004903:Erythrocyte Aggregation; D004912:Erythrocytes / Q000166:cytology; D005707:Gallic Acid / Q000737:chemistry* / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D057809:HEK293 Cells; D006461:Hemolysis; D006801:Humans; D010957:Plasmids / Q000008:administration & dosage* / Q000235:genetics; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D014162:Transfection
D050091:Dendrimers; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D011092:Polyethylene Glycols; D005707:Gallic Acid; D004247:DNA