Surface-functionalized polyurethane nanoparticles for targeted cancer therapy

Polymer nanoparticles (nps) have gained growing interest as carriers for anticancer drugs as they can target tumour tissues by both passive and active pathways. While the passive targeting mechanisms mainly rely on the small size of the carriers, active targeting requires surface modifications of the polymer core in order to introduce specific functionalities to actively recognize cancer cells. The present work proposes an innovative method for the preparation of surface-functionalized nps based on the use of biodegradable polyester- and polyester/ether-urethanes (PURs) embedding amino functionalities. Two polyurethanes were prepared, one based on just poly(ϵ-caprolactone) diol (PCL-PUR) and the other based on both PCL diol and poly(ethylene glycol) (PEG) (70/30 ratio, PCL-PEG-PUR). Nanoparticles of small size ranging between 150 and 200 nm and negative ζ potential (ranging from −18 mV to −27 mV) were obtained. Functional groups were exposed post nps preparation as confirmed by X-ray photoelectron spectroscopy, ninhydrin assay and 1H NMR, which evidenced a 24% tert-butyloxycarbonyl cleavage for PCL-PUR-NH2 nps and 29% for PCL-PEG-PUR-NH2 nps. The monoclonal antibody Herceptin (HER), which targets HER-2 receptors, was coupled through ethyl(dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) mediated chemistry. The optimal HER:NH2 ratio was determined to be 1:16 for the PEG-containing PUR and 1:8 for PCL-PUR. HER-nps maintained the intrinsic cytotoxicity of the antibody, as shown by the ca 50% decrease of HER-2-expressing HeLa cell viability. The results indicate that our protocol for surface functionalization of PUR nps, based on surface exposure of previously inserted functional groups followed by covalent coupling of biomolecules, is suitable for the preparation of nps for active recognition of target cells. © 2016 Society of Chemical Industry