Targeting nanomedicines to prostate cancer: evaluation of specificity of ligands to two different receptors in vivo

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Targeting nanomedicines to prostate cancer : evaluation of specificity of ligands to two different receptors in vivo. / Pearce, Amanda K.; Fuchs, Adrian V.; Fletcher, Nicholas L.; Thurecht, Kristofer J.

In: Pharmaceutical Research, Vol. 33, No. 10, 10.2016, p. 2388-2399.

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Pearce, Amanda K. ; Fuchs, Adrian V. ; Fletcher, Nicholas L. ; Thurecht, Kristofer J. / Targeting nanomedicines to prostate cancer : evaluation of specificity of ligands to two different receptors in vivo. In: Pharmaceutical Research. 2016 ; Vol. 33, No. 10. pp. 2388-2399.

Bibtex

@article{a107996a4cb445b99ddfb6d8368bac9a,
title = "Targeting nanomedicines to prostate cancer: evaluation of specificity of ligands to two different receptors in vivo",
abstract = "Purpose: This manuscript utilised in vivo multispectral imaging to demonstrate the efficacy of two different nanomedicine formulations for targeting prostate cancer. Methods: Pegylated hyperbranched polymers were labelled with fluorescent markers and targeting ligands against two different prostate cancer markers; prostate specific membrane antigen (PSMA) and the protein kinase, EphrinA2 receptor (EphA2). The PSMA targeted nanomedicine utilised a small molecule glutamate urea inhibitor of the protein, while the EphA2 targeted nanomedicine was conjugated to a single-chain variable fragment based on the antibody 4B3 that has shown high affinity to the receptor. Results: Hyperbranched polymers were synthesised bearing the different targeting ligands. In the case of the EphA2-targeting nanomedicine, significant in vitro uptake was observed in PC3 prostate cancer cells that overexpress the receptor, while low uptake was observed in LNCaP cells (that have minimal expression of this receptor). Conversely, the PSMA-targeted nanomedicine showed high uptake in LNCaP cells, with only minor uptake in the PC3 cells. In a dual-tumour xenograft mouse model, the nanomedicines showed high uptake in tumours in which the receptor was overexpressed, with only minimal non-specific accumulation in the low-expression tumours. Conclusions: This work highlighted the importance of clearly defining the target of interest in next-generation nanomedicines, and suggests that dual-targeting in such nanomedicines may be a means to achieve greater efficacy.",
keywords = "antibody, fluorescence imaging, molecular imaging, nanomedicine, nanotherapeutics",
author = "Pearce, {Amanda K.} and Fuchs, {Adrian V.} and Fletcher, {Nicholas L.} and Thurecht, {Kristofer J.}",
year = "2016",
month = oct,
doi = "10.1007/s11095-016-1945-x",
language = "English",
volume = "33",
pages = "2388--2399",
journal = "Pharmaceutical Research",
issn = "0724-8741",
publisher = "American Association of Pharmaceutical Scientists",
number = "10",

}

RIS

TY - JOUR

T1 - Targeting nanomedicines to prostate cancer

T2 - evaluation of specificity of ligands to two different receptors in vivo

AU - Pearce, Amanda K.

AU - Fuchs, Adrian V.

AU - Fletcher, Nicholas L.

AU - Thurecht, Kristofer J.

PY - 2016/10

Y1 - 2016/10

N2 - Purpose: This manuscript utilised in vivo multispectral imaging to demonstrate the efficacy of two different nanomedicine formulations for targeting prostate cancer. Methods: Pegylated hyperbranched polymers were labelled with fluorescent markers and targeting ligands against two different prostate cancer markers; prostate specific membrane antigen (PSMA) and the protein kinase, EphrinA2 receptor (EphA2). The PSMA targeted nanomedicine utilised a small molecule glutamate urea inhibitor of the protein, while the EphA2 targeted nanomedicine was conjugated to a single-chain variable fragment based on the antibody 4B3 that has shown high affinity to the receptor. Results: Hyperbranched polymers were synthesised bearing the different targeting ligands. In the case of the EphA2-targeting nanomedicine, significant in vitro uptake was observed in PC3 prostate cancer cells that overexpress the receptor, while low uptake was observed in LNCaP cells (that have minimal expression of this receptor). Conversely, the PSMA-targeted nanomedicine showed high uptake in LNCaP cells, with only minor uptake in the PC3 cells. In a dual-tumour xenograft mouse model, the nanomedicines showed high uptake in tumours in which the receptor was overexpressed, with only minimal non-specific accumulation in the low-expression tumours. Conclusions: This work highlighted the importance of clearly defining the target of interest in next-generation nanomedicines, and suggests that dual-targeting in such nanomedicines may be a means to achieve greater efficacy.

AB - Purpose: This manuscript utilised in vivo multispectral imaging to demonstrate the efficacy of two different nanomedicine formulations for targeting prostate cancer. Methods: Pegylated hyperbranched polymers were labelled with fluorescent markers and targeting ligands against two different prostate cancer markers; prostate specific membrane antigen (PSMA) and the protein kinase, EphrinA2 receptor (EphA2). The PSMA targeted nanomedicine utilised a small molecule glutamate urea inhibitor of the protein, while the EphA2 targeted nanomedicine was conjugated to a single-chain variable fragment based on the antibody 4B3 that has shown high affinity to the receptor. Results: Hyperbranched polymers were synthesised bearing the different targeting ligands. In the case of the EphA2-targeting nanomedicine, significant in vitro uptake was observed in PC3 prostate cancer cells that overexpress the receptor, while low uptake was observed in LNCaP cells (that have minimal expression of this receptor). Conversely, the PSMA-targeted nanomedicine showed high uptake in LNCaP cells, with only minor uptake in the PC3 cells. In a dual-tumour xenograft mouse model, the nanomedicines showed high uptake in tumours in which the receptor was overexpressed, with only minimal non-specific accumulation in the low-expression tumours. Conclusions: This work highlighted the importance of clearly defining the target of interest in next-generation nanomedicines, and suggests that dual-targeting in such nanomedicines may be a means to achieve greater efficacy.

KW - antibody

KW - fluorescence imaging

KW - molecular imaging

KW - nanomedicine

KW - nanotherapeutics

UR - http://www.scopus.com/inward/record.url?scp=84976615778&partnerID=8YFLogxK

U2 - 10.1007/s11095-016-1945-x

DO - 10.1007/s11095-016-1945-x

M3 - Article

C2 - 27225496

AN - SCOPUS:84976615778

VL - 33

SP - 2388

EP - 2399

JO - Pharmaceutical Research

JF - Pharmaceutical Research

SN - 0724-8741

IS - 10

ER -