Binary Targeting of siRNA to Hematologic Cancer Cells In Vivo Using Layer-by-Layer Nanoparticles

Ki Young Choi, Santiago Correa, Jouha Min, Jiahe Li, Sweta Roy, Kristiana H. Laccetti, Erik Dreaden, Stephanie Kong, Roun Heo, Young Hoon Roh, Edward C. Lawson, Peter A. Palmer, Paula T. Hammond

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number1900018
JournalAdvanced Functional Materials
Volume29
Issue number20
DOIs
Publication statusPublished - 2019 May 16

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Small Interfering RNA
Blood
cancer
Cells
Nanoparticles
nanoparticles
blood
Cell death
Polyelectrolytes
Cell culture
Antibodies
Animals
delivery
Ligands
Proteins
nuclease
animal models
leukemias
apoptosis
cells

All Science Journal Classification (ASJC) codes

  • Electronic, Optical and Magnetic Materials
  • Biomaterials
  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Electrochemistry

Cite this

Choi, K. Y., Correa, S., Min, J., Li, J., Roy, S., Laccetti, K. H., ... Hammond, P. T. (2019). Binary Targeting of siRNA to Hematologic Cancer Cells In Vivo Using Layer-by-Layer Nanoparticles. Advanced Functional Materials, 29(20), [1900018]. https://doi.org/10.1002/adfm.201900018
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. / Binary Targeting of siRNA to Hematologic Cancer Cells In Vivo Using Layer-by-Layer Nanoparticles. In: Advanced Functional Materials. 2019 ; Vol. 29, No. 20.
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Choi, KY, Correa, S, Min, J, Li, J, Roy, S, Laccetti, KH, Dreaden, E, Kong, S, Heo, R, Roh, YH, Lawson, EC, Palmer, PA & Hammond, PT 2019, 'Binary Targeting of siRNA to Hematologic Cancer Cells In Vivo Using Layer-by-Layer Nanoparticles', Advanced Functional Materials, vol. 29, no. 20, 1900018. https://doi.org/10.1002/adfm.201900018

Binary Targeting of siRNA to Hematologic Cancer Cells In Vivo Using Layer-by-Layer Nanoparticles. / 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.

In: Advanced Functional Materials, Vol. 29, No. 20, 1900018, 16.05.2019.

Research output: Contribution to journalArticle

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AU - Choi, Ki Young

AU - Correa, Santiago

AU - Min, Jouha

AU - Li, Jiahe

AU - Roy, Sweta

AU - Laccetti, Kristiana H.

AU - Dreaden, Erik

AU - Kong, Stephanie

AU - Heo, Roun

AU - Roh, Young Hoon

AU - Lawson, Edward C.

AU - Palmer, Peter A.

AU - Hammond, Paula T.

PY - 2019/5/16

Y1 - 2019/5/16

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