Assessment of the "Smart" Polymer Poly(sodium acrylate) for Anticancer Drug Targeting and Delivery

Abstract

The indiscriminate nature with which anticancer drugs attack all proliferating cells in the body leads to unwanted side effects. This project aimed to determine the potential of the "smart" polymer poly(acrylic acid) (PAA)/poly(sodium acrylate) (PNaA), in three different architectures (a linear and two branched versions), as an anticancer drug delivery system to help mitigate these side effects. PAA is considered a "smart" polymer because it has the unique ability to undergo a reversible ionisation change becoming PNaA in response to changes in environmental pH. This unique trait could be very beneficial for targeted cancer treatment as tumours have a more acidic microenvironment than surrounding non-cancerous tissues. The conjugation of the widely used anticancer drug cisplatin to PNaA (PNaA-Pt) was monitored by capillary electrophoresis in the critical conditions (CE-CC), and the amount of drug bound was determined by inductively coupled plasma mass spectrometry (ICP-MS). The branched versions of PNaA were found to have the largest binding capacity. Cytotoxicity studies of PNaA-Pt against cisplatin sensitive and resistant cells revealed PNaA-Pt can overcome the resistance phenotype, and produce at least a 765-fold improvement in potency compared to free cisplatin. No relationship between pH and potency was determined. The covalent attachment of a fluorescent probe, and the targeting ligand folic acid to PNaA were also monitored for the first time in this study by CE-CC. Confocal microscopy was used to visualise the uptake and cytoplasmic/nuclear localisation of PNaA. The knowledge obtained from this work demonstrates the potential of PAA/PNaA as an effective drug delivery system.