کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5032971 | 1370003 | 2017 | 9 صفحه PDF | دانلود رایگان |
1,5-Dihexadecyl N,N-diglutamyl-lysyl-L-glutamate (GGLG) liposomes were previously developed to enhance drug delivery efficiency in tumor cells owing to its pH-responsive properties. Herein, we report the modification of GGLG liposomes by conjugating a Fabâ² fragment of an ErbB2 antibody to the terminus of PEG (polyethylene glycol)-lipid (Fabâ²-GGLG liposomes). The conjugation of Fabâ² fragments did not affect the antibody activity, drug (doxorubicin, DOX) encapsulation efficiency, stability during storage or pH-sensitivity. However, the binding affinity of Fabâ²-GGLG liposomes was enhanced to ErbB2-overexpressing HCC1954 cells specifically, and the cell association increased 10-fold in comparison to GGLG liposomes. Consequently, intracellular DOX delivery was enhanced, with an increased cytotoxicity in HCC1954 cells (i.e., IC50 of 1.17 and 3.08 μg/mL for Fabâ²-GGLG-DOX and GGLG-DOX liposomes, respectively). Further, a significantly enhanced tumor growth inhibition was obtained in an ErbB2-overexpressing breast cancer-bearing mouse model. Therefore, a potent anticancer drug delivery system was constructed by the immunological modification of pH-sensitive liposomes.
Graphical AbstractAnti-ErB2 antibody-modified pH-sensitive (i.e., Fabâ²-GGLG) liposomes enhanced the cellular delivery and anticancer effect of doxorubicin (DOX) to ErB2-overexpressing breast cancer cells both in vitro and in vivo in comparison with unmodified liposomes.250
Journal: Nanomedicine: Nanotechnology, Biology and Medicine - Volume 13, Issue 3, April 2017, Pages 1219-1227