Binary Targeting of siRNA to Hematologic Cancer Cells In Vivo Using Layer-by-Layer Nanoparticles
- Authors
- Choi, Ki Young; Correa, Santiago; Min, Jouha; Li, Jiahe; Roy, Sweta; Laccetti, Kristiana H.; Dreaden, Erik; Kong, Stephanie; Heo, Roun; Roh, Young Hoon; Lawson, Edward C.; Palmer, Peter A.; Hammond, Paula T.
- Issue Date
- 2019-05-16
- Publisher
- WILEY-V C H VERLAG GMBH
- Citation
- ADVANCED FUNCTIONAL MATERIALS, v.29, no.20
- Abstract
- 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.
- Keywords
- DRUG; CHEMORESISTANCE; HYALURONAN; PROTEINS; ANTIBODY; FAMILY; POTENT; CD44; DRUG; CHEMORESISTANCE; HYALURONAN; PROTEINS; ANTIBODY; FAMILY; POTENT; CD44; B-cell lymphoma 2; hematologic cancer; layer-by-layer nanoparticles; lymphoma; siRNA
- ISSN
- 1616-301X
- URI
- https://pubs.kist.re.kr/handle/201004/119985
- DOI
- 10.1002/adfm.201900018
- Appears in Collections:
- KIST Article > 2019
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