Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6486380 | Biomaterials | 2015 | 8 Pages |
Abstract
Antibody-mediated therapies including antibody-drug conjugates (ADCs) have shown much potential in cancer treatment by tumor-targeted delivery of cytotoxic drugs. However, there is a limitation of payloads that can be delivered by ADCs. Integration of antibodies to drug-loaded nanocarriers broadens the applicability of antibodies to a wide range of therapeutics. Herein, we developed antibody fragment-installed polymeric micelles via maleimide-thiol conjugation for selectively delivering platinum drugs to pancreatic tumors. By tailoring the surface density of maleimide on the micelles, one tissue factor (TF)-targeting Fab' was conjugated to each carrier. Fab'-installed platinum-loaded micelles exhibited more than 15-fold increased cellular binding within 1 h and rapid cellular internalization compared to non-targeted micelles, leading to superior in vitro cytotoxicity. In vivo, Fab'-installed micelles significantly suppressed the growth of pancreatic tumor xenografts for more than 40 days, outperforming non-targeted micelles and free drugs. These results indicate the potential of Fab'-installed polymeric micelles for efficient drug delivery to solid tumors.
Related Topics
Physical Sciences and Engineering
Chemical Engineering
Bioengineering
Authors
Jooyeon Ahn, Yutaka Miura, Naoki Yamada, Tsukasa Chida, Xueying Liu, Ahram Kim, Ryuta Sato, Ryo Tsumura, Yoshikatsu Koga, Masahiro Yasunaga, Nobuhiro Nishiyama, Yasuhiro Matsumura, Horacio Cabral, Kazunori Kataoka,