Biomimetic Magnetic Nanostructures: A Theranostic Platform Targeting Lipid Metabolism and Immune Response in Lymphoma

Abhalaxmi Singh, Vikas Nandwana, Jonathan S. Rink, Soo Ryoon Ryoo, Tzu Hung Chen, Sean David Allen, Evan A. Scott, Leo I. Gordon, C. Shad Thaxton, Vinayak P. Dravid*

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

B-cell lymphoma cells depend upon cholesterol to maintain pro-proliferation and pro-survival signaling via the B-cell receptor. Targeted cholesterol depletion of lymphoma cells is an attractive therapeutic strategy. We report here high-density lipoprotein mimicking magnetic nanostructures (HDL-MNSs) that can bind to the high-affinity HDL receptor, scavenger receptor type B1 (SR-B1), and interfere with cholesterol flux mechanisms in SR-B1 receptor positive lymphoma cells, causing cellular cholesterol depletion. In addition, the MNS core can be utilized for its ability to generate heat under an external radio frequency field. The thermal activation of MNS can lead to both innate and adaptive antitumor immune responses by inducing the expression of heat shock proteins that lead to activation of antigen presenting cells and finally lymphocyte trafficking. In the present study, we demonstrate SR-B1 receptor mediated binding and cellular uptake of HDL-MNS and prevention of phagolysosome formation by transmission electron microscopy, fluorescence microscopy, and ICP-MS analysis. The combinational therapeutics of cholesterol depletion and thermal activation significantly improves therapeutic efficacy in SR-B1 expressing lymphoma cells. HDL-MNS reduces the T2 relaxation time under magnetic resonance imaging (MRI) more effectively compared with a commercially available contrast agent, and the specificity of HDL-MNS toward the SR-B1 receptor leads to differential contrast between SR-B1 positive and negative cells suggesting its utility in diagnostic imaging. Overall, we have demonstrated that HDL-MNSs have cell specific targeting efficiency, can modulate cholesterol efflux, can induce thermal activation mediated antitumor immune response, and possess high contrast under MRI, making it a promising theranostic platform in lymphoma.

Original languageEnglish (US)
Pages (from-to)10301-10311
Number of pages11
JournalACS nano
Volume13
Issue number9
DOIs
StatePublished - Sep 24 2019

Fingerprint

lipid metabolism
Scavenger Receptors
Cholesterol
biomimetics
Biomimetics
Lipoproteins
HDL Lipoproteins
Nanostructures
platforms
lipoproteins
cholesterol
Chemical activation
Magnetic resonance
Imaging techniques
cells
activation
Cells
depletion
Lymphocytes
Fluorescence microscopy

Keywords

  • SR-B1 receptor
  • antitumor immune response
  • high-density lipoprotein
  • lymphoma
  • magnetic nanostructure
  • thermal activation

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

Cite this

Singh, Abhalaxmi ; Nandwana, Vikas ; Rink, Jonathan S. ; Ryoo, Soo Ryoon ; Chen, Tzu Hung ; Allen, Sean David ; Scott, Evan A. ; Gordon, Leo I. ; Thaxton, C. Shad ; Dravid, Vinayak P. / Biomimetic Magnetic Nanostructures : A Theranostic Platform Targeting Lipid Metabolism and Immune Response in Lymphoma. In: ACS nano. 2019 ; Vol. 13, No. 9. pp. 10301-10311.
@article{0ff6932541ca4244a9c72e80b3bdcd45,
title = "Biomimetic Magnetic Nanostructures: A Theranostic Platform Targeting Lipid Metabolism and Immune Response in Lymphoma",
abstract = "B-cell lymphoma cells depend upon cholesterol to maintain pro-proliferation and pro-survival signaling via the B-cell receptor. Targeted cholesterol depletion of lymphoma cells is an attractive therapeutic strategy. We report here high-density lipoprotein mimicking magnetic nanostructures (HDL-MNSs) that can bind to the high-affinity HDL receptor, scavenger receptor type B1 (SR-B1), and interfere with cholesterol flux mechanisms in SR-B1 receptor positive lymphoma cells, causing cellular cholesterol depletion. In addition, the MNS core can be utilized for its ability to generate heat under an external radio frequency field. The thermal activation of MNS can lead to both innate and adaptive antitumor immune responses by inducing the expression of heat shock proteins that lead to activation of antigen presenting cells and finally lymphocyte trafficking. In the present study, we demonstrate SR-B1 receptor mediated binding and cellular uptake of HDL-MNS and prevention of phagolysosome formation by transmission electron microscopy, fluorescence microscopy, and ICP-MS analysis. The combinational therapeutics of cholesterol depletion and thermal activation significantly improves therapeutic efficacy in SR-B1 expressing lymphoma cells. HDL-MNS reduces the T2 relaxation time under magnetic resonance imaging (MRI) more effectively compared with a commercially available contrast agent, and the specificity of HDL-MNS toward the SR-B1 receptor leads to differential contrast between SR-B1 positive and negative cells suggesting its utility in diagnostic imaging. Overall, we have demonstrated that HDL-MNSs have cell specific targeting efficiency, can modulate cholesterol efflux, can induce thermal activation mediated antitumor immune response, and possess high contrast under MRI, making it a promising theranostic platform in lymphoma.",
keywords = "SR-B1 receptor, antitumor immune response, high-density lipoprotein, lymphoma, magnetic nanostructure, thermal activation",
author = "Abhalaxmi Singh and Vikas Nandwana and Rink, {Jonathan S.} and Ryoo, {Soo Ryoon} and Chen, {Tzu Hung} and Allen, {Sean David} and Scott, {Evan A.} and Gordon, {Leo I.} and Thaxton, {C. Shad} and Dravid, {Vinayak P.}",
year = "2019",
month = "9",
day = "24",
doi = "10.1021/acsnano.9b03727",
language = "English (US)",
volume = "13",
pages = "10301--10311",
journal = "ACS Nano",
issn = "1936-0851",
publisher = "American Chemical Society",
number = "9",

}

Biomimetic Magnetic Nanostructures : A Theranostic Platform Targeting Lipid Metabolism and Immune Response in Lymphoma. / Singh, Abhalaxmi; Nandwana, Vikas; Rink, Jonathan S.; Ryoo, Soo Ryoon; Chen, Tzu Hung; Allen, Sean David; Scott, Evan A.; Gordon, Leo I.; Thaxton, C. Shad; Dravid, Vinayak P.

In: ACS nano, Vol. 13, No. 9, 24.09.2019, p. 10301-10311.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Biomimetic Magnetic Nanostructures

T2 - A Theranostic Platform Targeting Lipid Metabolism and Immune Response in Lymphoma

AU - Singh, Abhalaxmi

AU - Nandwana, Vikas

AU - Rink, Jonathan S.

AU - Ryoo, Soo Ryoon

AU - Chen, Tzu Hung

AU - Allen, Sean David

AU - Scott, Evan A.

AU - Gordon, Leo I.

AU - Thaxton, C. Shad

AU - Dravid, Vinayak P.

PY - 2019/9/24

Y1 - 2019/9/24

N2 - B-cell lymphoma cells depend upon cholesterol to maintain pro-proliferation and pro-survival signaling via the B-cell receptor. Targeted cholesterol depletion of lymphoma cells is an attractive therapeutic strategy. We report here high-density lipoprotein mimicking magnetic nanostructures (HDL-MNSs) that can bind to the high-affinity HDL receptor, scavenger receptor type B1 (SR-B1), and interfere with cholesterol flux mechanisms in SR-B1 receptor positive lymphoma cells, causing cellular cholesterol depletion. In addition, the MNS core can be utilized for its ability to generate heat under an external radio frequency field. The thermal activation of MNS can lead to both innate and adaptive antitumor immune responses by inducing the expression of heat shock proteins that lead to activation of antigen presenting cells and finally lymphocyte trafficking. In the present study, we demonstrate SR-B1 receptor mediated binding and cellular uptake of HDL-MNS and prevention of phagolysosome formation by transmission electron microscopy, fluorescence microscopy, and ICP-MS analysis. The combinational therapeutics of cholesterol depletion and thermal activation significantly improves therapeutic efficacy in SR-B1 expressing lymphoma cells. HDL-MNS reduces the T2 relaxation time under magnetic resonance imaging (MRI) more effectively compared with a commercially available contrast agent, and the specificity of HDL-MNS toward the SR-B1 receptor leads to differential contrast between SR-B1 positive and negative cells suggesting its utility in diagnostic imaging. Overall, we have demonstrated that HDL-MNSs have cell specific targeting efficiency, can modulate cholesterol efflux, can induce thermal activation mediated antitumor immune response, and possess high contrast under MRI, making it a promising theranostic platform in lymphoma.

AB - B-cell lymphoma cells depend upon cholesterol to maintain pro-proliferation and pro-survival signaling via the B-cell receptor. Targeted cholesterol depletion of lymphoma cells is an attractive therapeutic strategy. We report here high-density lipoprotein mimicking magnetic nanostructures (HDL-MNSs) that can bind to the high-affinity HDL receptor, scavenger receptor type B1 (SR-B1), and interfere with cholesterol flux mechanisms in SR-B1 receptor positive lymphoma cells, causing cellular cholesterol depletion. In addition, the MNS core can be utilized for its ability to generate heat under an external radio frequency field. The thermal activation of MNS can lead to both innate and adaptive antitumor immune responses by inducing the expression of heat shock proteins that lead to activation of antigen presenting cells and finally lymphocyte trafficking. In the present study, we demonstrate SR-B1 receptor mediated binding and cellular uptake of HDL-MNS and prevention of phagolysosome formation by transmission electron microscopy, fluorescence microscopy, and ICP-MS analysis. The combinational therapeutics of cholesterol depletion and thermal activation significantly improves therapeutic efficacy in SR-B1 expressing lymphoma cells. HDL-MNS reduces the T2 relaxation time under magnetic resonance imaging (MRI) more effectively compared with a commercially available contrast agent, and the specificity of HDL-MNS toward the SR-B1 receptor leads to differential contrast between SR-B1 positive and negative cells suggesting its utility in diagnostic imaging. Overall, we have demonstrated that HDL-MNSs have cell specific targeting efficiency, can modulate cholesterol efflux, can induce thermal activation mediated antitumor immune response, and possess high contrast under MRI, making it a promising theranostic platform in lymphoma.

KW - SR-B1 receptor

KW - antitumor immune response

KW - high-density lipoprotein

KW - lymphoma

KW - magnetic nanostructure

KW - thermal activation

UR - http://www.scopus.com/inward/record.url?scp=85072800156&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85072800156&partnerID=8YFLogxK

U2 - 10.1021/acsnano.9b03727

DO - 10.1021/acsnano.9b03727

M3 - Article

C2 - 31487458

AN - SCOPUS:85072800156

VL - 13

SP - 10301

EP - 10311

JO - ACS Nano

JF - ACS Nano

SN - 1936-0851

IS - 9

ER -