|
|
|
|
LEADER |
02574 am a22003133u 4500 |
001 |
125799 |
042 |
|
|
|a dc
|
100 |
1 |
0 |
|a Choi, Ki Young
|e author
|
100 |
1 |
0 |
|a Massachusetts Institute of Technology. Department of Chemical Engineering
|e contributor
|
100 |
1 |
0 |
|a Koch Institute for Integrative Cancer Research at MIT
|e contributor
|
700 |
1 |
0 |
|a Correa Echavarria, Santiago
|e author
|
700 |
1 |
0 |
|a Min, Jouha
|e author
|
700 |
1 |
0 |
|a Li, Jiahe
|e author
|
700 |
1 |
0 |
|a Roy, Sweta
|e author
|
700 |
1 |
0 |
|a Laccetti, Kristiana H
|e author
|
700 |
1 |
0 |
|a Dreaden, Erik
|e author
|
700 |
1 |
0 |
|a Kong, Stephanie
|e author
|
700 |
1 |
0 |
|a Heo, Roun
|e author
|
700 |
1 |
0 |
|a Roh, Young Hoon
|e author
|
700 |
1 |
0 |
|a Lawson, Edward C.
|e author
|
700 |
1 |
0 |
|a Palmer, Peter A.
|e author
|
700 |
1 |
0 |
|a Hammond, Paula T
|e author
|
245 |
0 |
0 |
|a Binary Targeting of siRNA to Hematologic Cancer Cells In Vivo Using Layer‐by‐Layer Nanoparticles
|
260 |
|
|
|b Wiley,
|c 2020-06-15T18:02:39Z.
|
856 |
|
|
|z Get fulltext
|u https://hdl.handle.net/1721.1/125799
|
520 |
|
|
|a Using siRNA therapeutics to treat hematologic malignancies has been unsuccessful because blood cancer cells exhibit remarkable resistance to standard transfection methods. Herein, the successful delivery of siRNA therapeutics with a dual-targeted, layer-by-layer nanoparticle (LbL-NP) is reported. The LbL-NP protects siRNA from nucleases in the bloodstream by embedding it within polyelectrolyte layers that coat a polymeric core. The outermost layer consists of hyaluronic acid (a CD44-ligand) covalently conjugated to CD20 antibodies. The CD20/CD44 dual-targeting outer layer provides precise binding to blood cancer cells, followed by receptor-mediated endocytosis of the LbL-NP. This siRNA delivery platform is used to silence B-cell lymphoma 2 (BCL-2), a pro-survival protein, in vitro and in vivo. The dual-targeting approach significantly enhances internalization of BCL-2 siRNA in lymphoma and leukemia cells, which leads to significant downregulation of BCL-2 expression. Systemic administration of the dual-targeted, siRNA-loaded nanoparticle induces apoptosis and hampers proliferation of blood cancer cells, both in cell culture and in orthotopic non-Hodgkin's lymphoma animal models. These results provide the basis for approaches to targeting blood-borne cancers and other diseases and suggest that LbL nanoassemblies are a promising approach for delivering therapeutic siRNA to hematopoetic cell types that are known to evade transfection by other means.
|
546 |
|
|
|a en
|
655 |
7 |
|
|a Article
|
773 |
|
|
|t Advanced Functional Materials
|