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. and Thurecht, Kristofer J. (2016) Targeting Nanomedicines to Prostate Cancer: Evaluation of Specificity of Ligands to Two Different Receptors In Vivo. Pharmaceutical Research, 33 10: 1-12. doi:10.1007/s11095-016-1945-x


Author Pearce, Amanda K.
Fuchs, Adrian V.
Fletcher, Nicholas L.
Thurecht, Kristofer J.
Title Targeting Nanomedicines to Prostate Cancer: Evaluation of Specificity of Ligands to Two Different Receptors In Vivo
Journal name Pharmaceutical Research   Check publisher's open access policy
ISSN 0724-8741
1573-904X
Publication date 2016-05-25
Year available 2016
Sub-type Article (original research)
DOI 10.1007/s11095-016-1945-x
Open Access Status Not yet assessed
Volume 33
Issue 10
Start page 1
End page 12
Total pages 12
Place of publication New York, NY United States
Publisher Springer
Language eng
Abstract This manuscript utilised in vivo multispectral imaging to demonstrate the efficacy of two different nanomedicine formulations for targeting prostate cancer.
Formatted 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 singlechain 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.
Keyword Chemistry, Multidisciplinary
Pharmacology & Pharmacy
Chemistry
Pharmacology & Pharmacy
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID APP1099321
FT110100284
CE140100036
Institutional Status UQ

 
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Created: Mon, 13 Jun 2016, 20:52:58 EST by Adrian Fuchs on behalf of Aust Institute for Bioengineering & Nanotechnology