Leyuan Xu1,2,3, Shannon Kittrell4, W Andrew Yeudall5,6, Hu Yang1,7,8. 1. Department of Chemical & Life Science Engineering, Virginia Commonwealth University, Richmond, VA 23284, USA. 2. Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23284, USA. 3. Department of Internal Medicine, Yale University, New Haven, CT 06520, USA. 4. Department of Biochemistry, Virginia Commonwealth University, Richmond, VA 23298, USA. 5. Department of Oral Biology, Augusta University, Augusta, GA 30912, USA. 6. Molecular Oncology & Biomarkers Program, Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA. 7. Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA 23298, USA. 8. Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.
Abstract
AIM: Folic acid (FA)-decorated polyamidoamine dendrimer G4 (G4-FA) was synthesized and studied for targeted delivery of genes to head and neck cancer cells expressing high levels of folate receptors (FRs). METHODS: Cellular uptake, targeting specificity, cytocompatibility and transfection efficiency were evaluated. RESULTS: G4-FA competes with free FA for the same binding site. G4-FA facilitates the cellular uptake of DNA plasmids in a FR-dependent manner and selectively delivers plasmids to FR-high cells, leading to enhanced gene expression. CONCLUSION: G4-FA is a suitable vector to deliver genes selectively to head and neck cancer cells. The fundamental understandings of G4-FA as a vector and its encouraging transfection results for head and neck cancer cells provided support for its further testing in vivo.
AIM: Folic acid (FA)-decorated polyamidoamine dendrimer G4 (G4-FA) was synthesized and studied for targeted delivery of genes to head and neck cancer cells expressing high levels of folate receptors (FRs). METHODS: Cellular uptake, targeting specificity, cytocompatibility and transfection efficiency were evaluated. RESULTS:G4-FA competes with free FA for the same binding site. G4-FA facilitates the cellular uptake of DNA plasmids in a FR-dependent manner and selectively delivers plasmids to FR-high cells, leading to enhanced gene expression. CONCLUSION:G4-FA is a suitable vector to deliver genes selectively to head and neck cancer cells. The fundamental understandings of G4-FA as a vector and its encouraging transfection results for head and neck cancer cells provided support for its further testing in vivo.
Entities:
Keywords:
PAMAM dendrimer; folate receptor targeting; gene therapy; head and neck squamous cell carcinoma
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