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Issue 24, 2014
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Development of a polymer theranostic for prostate cancer

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Abstract

Theranostics offers an improved treatment strategy for prostate cancer by facilitating simultaneous targeting of tumour cells with subsequent drug delivery and imaging. In this report we describe the synthesis of hyperbranched polymers that are biocompatible, can specifically target and be internalised by prostate cancer cells (through targeting of prostate-specific membrane antigen – PSMA) and ultimately facilitate controlled delivery of a model drug. The theranostic also incorporates a far-red fluorescent dye that allows tracking of the polymer via optical imaging. Controlled synthesis of the polymer is achieved via reversible addition fragmentation chain transfer polymerisation of polyethylene glycol monomethyl methacrylate, with ethylene glycol dimethacrylate as the branching agent. Incorporation of 20 mol% of an hydrazide-methacrylate monomer allows post-ligation of a model drug, fluorene-2-carboxaldehyde, through a hydrolytically-degradable hydrazone linkage. The rate of degradation of this particular linker was enhanced at endosomal pH (pH = 5.5) where ∼95% of the model drug was released in 4 hours compared to less than 5% released over the same period at physiological pH. The theranostic showed high uptake into prostate cancer cells expressing prostate-specific membrane antigen, while minimal uptake was observed in PC3 cells negative for PSMA, highlighting the enhanced efficacy of the targeting ligand.

Graphical abstract: Development of a polymer theranostic for prostate cancer

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Publication details

The article was received on 22 Jul 2014, accepted on 21 Aug 2014 and first published on 04 Sep 2014


Article type: Paper
DOI: 10.1039/C4PY00999A
Polym. Chem., 2014,5, 6932-6942

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    Development of a polymer theranostic for prostate cancer

    A. K. Pearce, B. E. Rolfe, P. J. Russell, B. W.-C. Tse, A. K. Whittaker, A. V. Fuchs and K. J. Thurecht, Polym. Chem., 2014, 5, 6932
    DOI: 10.1039/C4PY00999A

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