Biomimetic, synthetic HDL nanostructures for lymphoma

Shuo Yang; Marina G. Damiano; Heng Zhang; Sushant Tripathy; Andrea J. Luthi; Jonathan S. Rink; Andrey V. Ugolkov; Amareshwar T K Singh; Sandeep S. Dave; Leo I. Gordon; C. Shad Thaxton

doi:10.1073/pnas.1213657110

Biomimetic, synthetic HDL nanostructures for lymphoma

Shuo Yang, Marina G. Damiano, Heng Zhang, Sushant Tripathy, Andrea J. Luthi, Jonathan S. Rink, Andrey V. Ugolkov, Amareshwar T K Singh, Sandeep S. Dave, Leo I. Gordon^*, C. Shad Thaxton

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

121 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	2511-2516
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	110
Issue number	7
DOIs	https://doi.org/10.1073/pnas.1213657110
State	Published - Feb 12 2013

Keywords

Biologic
Nanotechnology
Therapy

ASJC Scopus subject areas

General

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1073/pnas.1213657110

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title = "Biomimetic, synthetic HDL nanostructures for lymphoma",

abstract = "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.",

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author = "Shuo Yang and Damiano, {Marina G.} and Heng Zhang and Sushant Tripathy and Luthi, {Andrea J.} and Rink, {Jonathan S.} and Ugolkov, {Andrey V.} and Singh, {Amareshwar T K} and Dave, {Sandeep S.} and Gordon, {Leo I.} and Thaxton, {C. Shad}",

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AU - Yang, Shuo

AU - Damiano, Marina G.

AU - Zhang, Heng

AU - Tripathy, Sushant

AU - Luthi, Andrea J.

AU - Rink, Jonathan S.

AU - Ugolkov, Andrey V.

AU - Singh, Amareshwar T K

AU - Dave, Sandeep S.

AU - Gordon, Leo I.

AU - Thaxton, C. Shad

PY - 2013/2/12

Y1 - 2013/2/12

N2 - 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.

AB - 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.

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KW - Nanotechnology

KW - Therapy

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Biomimetic, synthetic HDL nanostructures for lymphoma

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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