Biomimetic, synthetic HDL nanostructures for lymphoma.
New therapies that challenge existing paradigms are needed for the treatment of cancer. We report a nanoparticle-enabled therapeutic approach to B-cell lymphoma using synthetic high density lipoprotein nanoparticles (HDL-NPs). HDL-NPs are synthesized using a gold nanoparticle template to control conjugate size and ensure a spherical shape. Like natural HDLs, biomimetic HDL-NPs target scavenger receptor type B-1, a high-affinity HDL receptor expressed by lymphoma cells. Functionally, compared with natural HDL, the gold NP template enables differential manipulation of cellular cholesterol flux in lymphoma cells, promoting cellular cholesterol efflux and limiting cholesterol delivery. This combination of scavenger receptor type B-1 binding and relative cholesterol starvation selectively induces apoptosis. HDL-NP treatment of mice bearing B-cell lymphoma xenografts selectively inhibits B-cell lymphoma growth. As such, HDL-NPs are biofunctional therapeutic agents, whose mechanism of action is enabled by the presence of a synthetic nanotemplate. HDL-NPs are active in B-cell lymphomas and potentially, other malignancies or diseases of pathologic cholesterol accumulation.
Department of Medicine, Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Shuo
S
Yang
Marina G
MG
Damiano
Heng
H
Zhang
Sushant
S
Tripathy
Andrea J
AJ
Luthi
Jonathan S
JS
Rink
Andrey V
AV
Ugolkov
Amareshwar T K
AT
Singh
Sandeep S
SS
Dave
Leo I
LI
Gordon
C Shad
CS
Thaxton
D000818:Animals; D017304:Annexin A5; D017209:Apoptosis / Q000502:physiology; D032701:Biomimetics / Q000379:methods*; D015153:Blotting, Western; D016650:Fluorescein-5-isothiocyanate; D006801:Humans; D015151:Immunoblotting; D019169:Jurkat Cells; D008075:Lipoproteins, HDL / Q000378:metabolism / Q000627:therapeutic use*; D016393:Lymphoma, B-Cell / Q000188:drug therapy*; D013058:Mass Spectrometry; D053768:Metal Nanoparticles / Q000627:therapeutic use*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D051122:Scavenger Receptors, Class B / Q000378:metabolism
D017304:Annexin A5; D008075:Lipoproteins, HDL; D051122:Scavenger Receptors, Class B; D016650:Fluorescein-5-isothiocyanate