| Autor: |
Kamra M; Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, India.; Technical Research Centre, Indian Association for the Cultivation of Science, Kolkata 700032, India., Maiti B; School of Applied and Interdisciplinary Sciences, Indian Association for the Cultivation of Science, Kolkata 700032, India., Saha P; School of Applied and Interdisciplinary Sciences, Indian Association for the Cultivation of Science, Kolkata 700032, India., Karande AA; Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India., Bhattacharya S; Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, India.; Technical Research Centre, Indian Association for the Cultivation of Science, Kolkata 700032, India.; School of Applied and Interdisciplinary Sciences, Indian Association for the Cultivation of Science, Kolkata 700032, India. |
| Abstrakt: |
Construction of a vitamin E-based liposomal biomaterial and its ability to deliver therapeutic genes selectively across liver cancer cells are demonstrated herein. In humans, liver regulates the levels of α-tocopherol, i.e., vitamin E, and hepatic cells carry the machinery for its transport. To exploit the presence of tocopherol transport protein, we have selected an efficient gene transfecting α-tocopherol-based twin lipid bearing a hydroxyethylated headgroup and octamethylene spacer (TH8S) for liposome formation. Also, based on the abundancy of the low-density lipoprotein receptor (LDLr) on the cellular surface in the case of hepatocellular carcinoma, anti-LDLr monoclonal antibody is used to confer the targeting ability to liposomes. A facile thiol-maleimide click chemistry is used for antibody decoration on the liposomal surface. Selective delivery of reporter and therapeutic genes (GFP and p53) to cells of hepatic origin was observed using anti-LDLr-tagged TH8S liposomes. Cellular internalization by receptor-mediated endocytosis renders the bioconjugate highly specific as well as highly efficient. Compatibility of the designed material with human blood points to its safety of use in systemic circulation thereby highlighting its in vivo potential. Thus, we report here a versatile biomaterial derived from an essential vitamin that promises potential for targeted suicidal gene therapy. |
