作者: Pierre Simard , Jean-Christophe Leroux
DOI: 10.1016/J.IJPHARM.2009.05.013
关键词: Internalization 、 Monoclonal antibody 、 Endocytosis 、 Flow cytometry 、 Biophysics 、 Biochemistry 、 Endosome 、 Chemistry 、 Liposome 、 Cytotoxicity 、 Antigen
摘要: A promising avenue in cancer therapy using liposomal formulations is the combination of site-specific delivery with triggered drug release. The use trigger mechanisms liposomes could be relevant for drugs susceptible to lysosomal hydrolytic/enzymatic degradation. Here, we propose a polymeric pH-sensitive liposome system that designed release its content inside endosomes through polymer structural change following receptor-mediated internalization. Specifically, immunoliposomes (ILs) were obtained by including terminally alkylated copolymer N-isopropylacrylamide (NIPAM) bilayer and coupling anti-CD33 monoclonal antibody target leukemic cells. In vitro encapsulated fluorescent probes cytosine arabinoside (ara-C) revealed pH-sensitivity vector was retained presence upon incubation plasma. Flow cytometry confocal microscopy analyses demonstrated ILs efficiently internalized various CD33+ cell lines while limited interaction found decorated an isotype-matched control antibody. Finally, ILs-CD33 formulation exhibited highest cytotoxicity against HL60 cells, confirming role NIPAM promoting escape intact ara-C endosomes. These results suggest this beneficial treatment acute myeloid leukemia.