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All-trans-retinoic acid (ATRA)-grafted polymeric gene carriers for nuclear translocation and cell growth control

Paper ID Volume ID Publish Year Pages File Format Full-Text
10405 683 2009 11 PDF Available
Title
All-trans-retinoic acid (ATRA)-grafted polymeric gene carriers for nuclear translocation and cell growth control
Abstract

Polyethyleneimine (PEI)-g-All-trans-retinoic acid (ATRA) (designated as PRA) was synthesized as a gene carrier. ATRA at its low concentration is known to be linked to nuclear translocation and cell cycle control (either proliferation or growth arrest) depending on its binding protein in cells. The cytotoxicity of PRA conjugates was lower than that of PEI and was gradually reduced as increasing ATRA graft ratios. The resulting nanosized and positively charged PRA/pDNA complexes showed lower transfection efficiency than the PEI/pDNA complexes (N/P = 10) against NIH3T3 which is less sensitive to ATRA in cell growth and more sensitive HeLa cells. However, when a mixed gene complex of PEI and PRA was applied in an effort to reduce the ATRA contents, their NIH3T3 transfection evidenced effective nuclear translocation and induced 2- to 4-fold better transfection efficiency as compared with the PEI/pDNA complexes. When the PEI/pDNA complexes were utilized to transfect HeLa cells, free ATRA treatment reduced their cellular uptake and transfection efficiency. These findings show that the NIH3T3 cells against ATRA-mediated growth arrest would not damage the PRA-mediated transfection enhancement resulting from the facilitated nuclear translocation of polyplexes or pDNA. The more ATRA-sensitivity in growth arrest of HeLa cells would reduce the transfection efficiency of ATRA-incorporated polyplexes. The transfection capability of gene by newly synthesized PRA conjugates to cells is differentiated by their ATRA-sensitivity to nuclear translocation and cell growth control.

Keywords
All-trans-retinoic acid (ATRA); Polyethyleneimine (PEI); Nuclear translocation; Cell cycle control
First Page Preview
All-trans-retinoic acid (ATRA)-grafted polymeric gene carriers for nuclear translocation and cell growth control
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 30, Issue 13, May 2009, Pages 2642–2652
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering