Findings questioning the involvement of Sigma-1 receptor in the uptake of anisamide-decorated particles

Athanasia Dasargyri, Pablo Hervella, Ailsa Christiansen, Steven T. Proulx, Michael Detmar, Jean Christophe Leroux*

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Anisamide is a small benzamide previously suggested as a tumor-targeting ligand for nanocarriers and it has been shown to enhance tumor uptake in vitro as well as in vivo when grafted on the nanoparticle surface. Anisamide has been hypothesized to interact with the Sigma-1 receptor, based on the binding of larger benzamides, which contain anisamide in their structure, to this receptor. However, the interaction between anisamide and Sigma-1 receptor has never been thoroughly studied. We developed fluorescent PEGylated particles decorated with anisamide, which were preferentially taken up in vitro by melanoma cells compared to macrophages. The anisamide-decorated particles were used to study their interaction with the Sigma-1 receptor. The absence of competition of Sigma-1 receptor ligands for the particle uptake was a first indication that the receptor might not be involved in the uptake process. In addition, the extent of particle uptake did not correlate with the levels of cellular expression of Sigma-1 receptor in the cell models tested. Immunostaining of the receptor on melanoma cells revealed intracellular localization, indirectly excluding the possibility of anisamide binding to the receptor when grafted on the particles. All these data question the previously suggested Sigma-1 receptor-mediated uptake of the anisamide-decorated particles, a finding which may have an impact on the use of anisamide as a targeting ligand.

OriginalsprogEngelsk
TidsskriftJournal of Controlled Release
Vol/bind224
Sider (fra-til)229-238
ISSN0168-3659
DOI
StatusUdgivet - 2016

Fingeraftryk

Ligands
Melanoma
sigma-1 receptor
Neoplasms
Macrophages
In Vitro Techniques

Citer dette

Dasargyri, Athanasia ; Hervella, Pablo ; Christiansen, Ailsa ; Proulx, Steven T. ; Detmar, Michael ; Leroux, Jean Christophe. / Findings questioning the involvement of Sigma-1 receptor in the uptake of anisamide-decorated particles. I: Journal of Controlled Release. 2016 ; Bind 224. s. 229-238.
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title = "Findings questioning the involvement of Sigma-1 receptor in the uptake of anisamide-decorated particles",
abstract = "Anisamide is a small benzamide previously suggested as a tumor-targeting ligand for nanocarriers and it has been shown to enhance tumor uptake in vitro as well as in vivo when grafted on the nanoparticle surface. Anisamide has been hypothesized to interact with the Sigma-1 receptor, based on the binding of larger benzamides, which contain anisamide in their structure, to this receptor. However, the interaction between anisamide and Sigma-1 receptor has never been thoroughly studied. We developed fluorescent PEGylated particles decorated with anisamide, which were preferentially taken up in vitro by melanoma cells compared to macrophages. The anisamide-decorated particles were used to study their interaction with the Sigma-1 receptor. The absence of competition of Sigma-1 receptor ligands for the particle uptake was a first indication that the receptor might not be involved in the uptake process. In addition, the extent of particle uptake did not correlate with the levels of cellular expression of Sigma-1 receptor in the cell models tested. Immunostaining of the receptor on melanoma cells revealed intracellular localization, indirectly excluding the possibility of anisamide binding to the receptor when grafted on the particles. All these data question the previously suggested Sigma-1 receptor-mediated uptake of the anisamide-decorated particles, a finding which may have an impact on the use of anisamide as a targeting ligand.",
keywords = "Anisamide, Drug targeting, Receptor-mediated endocytosis, Sigma-1 receptor",
author = "Athanasia Dasargyri and Pablo Hervella and Ailsa Christiansen and Proulx, {Steven T.} and Michael Detmar and Leroux, {Jean Christophe}",
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Findings questioning the involvement of Sigma-1 receptor in the uptake of anisamide-decorated particles. / Dasargyri, Athanasia; Hervella, Pablo; Christiansen, Ailsa; Proulx, Steven T.; Detmar, Michael; Leroux, Jean Christophe.

I: Journal of Controlled Release, Bind 224, 2016, s. 229-238.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Findings questioning the involvement of Sigma-1 receptor in the uptake of anisamide-decorated particles

AU - Dasargyri, Athanasia

AU - Hervella, Pablo

AU - Christiansen, Ailsa

AU - Proulx, Steven T.

AU - Detmar, Michael

AU - Leroux, Jean Christophe

PY - 2016

Y1 - 2016

N2 - Anisamide is a small benzamide previously suggested as a tumor-targeting ligand for nanocarriers and it has been shown to enhance tumor uptake in vitro as well as in vivo when grafted on the nanoparticle surface. Anisamide has been hypothesized to interact with the Sigma-1 receptor, based on the binding of larger benzamides, which contain anisamide in their structure, to this receptor. However, the interaction between anisamide and Sigma-1 receptor has never been thoroughly studied. We developed fluorescent PEGylated particles decorated with anisamide, which were preferentially taken up in vitro by melanoma cells compared to macrophages. The anisamide-decorated particles were used to study their interaction with the Sigma-1 receptor. The absence of competition of Sigma-1 receptor ligands for the particle uptake was a first indication that the receptor might not be involved in the uptake process. In addition, the extent of particle uptake did not correlate with the levels of cellular expression of Sigma-1 receptor in the cell models tested. Immunostaining of the receptor on melanoma cells revealed intracellular localization, indirectly excluding the possibility of anisamide binding to the receptor when grafted on the particles. All these data question the previously suggested Sigma-1 receptor-mediated uptake of the anisamide-decorated particles, a finding which may have an impact on the use of anisamide as a targeting ligand.

AB - Anisamide is a small benzamide previously suggested as a tumor-targeting ligand for nanocarriers and it has been shown to enhance tumor uptake in vitro as well as in vivo when grafted on the nanoparticle surface. Anisamide has been hypothesized to interact with the Sigma-1 receptor, based on the binding of larger benzamides, which contain anisamide in their structure, to this receptor. However, the interaction between anisamide and Sigma-1 receptor has never been thoroughly studied. We developed fluorescent PEGylated particles decorated with anisamide, which were preferentially taken up in vitro by melanoma cells compared to macrophages. The anisamide-decorated particles were used to study their interaction with the Sigma-1 receptor. The absence of competition of Sigma-1 receptor ligands for the particle uptake was a first indication that the receptor might not be involved in the uptake process. In addition, the extent of particle uptake did not correlate with the levels of cellular expression of Sigma-1 receptor in the cell models tested. Immunostaining of the receptor on melanoma cells revealed intracellular localization, indirectly excluding the possibility of anisamide binding to the receptor when grafted on the particles. All these data question the previously suggested Sigma-1 receptor-mediated uptake of the anisamide-decorated particles, a finding which may have an impact on the use of anisamide as a targeting ligand.

KW - Anisamide

KW - Drug targeting

KW - Receptor-mediated endocytosis

KW - Sigma-1 receptor

U2 - 10.1016/j.jconrel.2016.01.021

DO - 10.1016/j.jconrel.2016.01.021

M3 - Journal article

VL - 224

SP - 229

EP - 238

JO - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

ER -