Surface‐functionalized polyurethane nanoparticles for targeted cancer therapy

Abstract

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( -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 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 1 H NMR, which evidenced a 24% tert-butyloxycarbonyl cleavage for PCL-PUR-NH 2 nps and 29% for PCL-PEG-PUR-NH 2 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:NH 2 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.

Polymers and Polymer Nanocomposites for Cancer Therapy

“…Polyester/ether urethanes (PURs) can be an interesting alternative for the preparation of nanocarriers in the place of traditionally used biodegradable polyesters. PURs can be easily designed to modulate a hydrophilic/hydrophobic balance and to embed specific functionalities, thus representing a promising solution as a targeted delivery system [17].…”

“…Due to a precise stimuli response effect, drug delivery systems can control the release, reduce the damage to normal tissue and organs, and decrease side effects [16].Polyester/ether urethanes (PURs) can be an interesting alternative for the preparation of nanocarriers in the place of traditionally used biodegradable polyesters. PURs can be easily designed to modulate a hydrophilic/hydrophobic balance and to embed specific functionalities, thus representing a promising solution as a targeted delivery system [17].Poly (cyclotriphosphazene-co-dopamine) microspheres as controlled drug carriers were investigated using acriflavine as a model drug. The microspheres had a 19.5-mgg −1 drug storage capacity and sustained release properties of up to 7 days, with 29% (pH 5.0) and 47% (pH 7.4) at 37 • C [18].Nanopolymers such as poly(lactic acid) (PLA), PEG, poly(vinyl pirrolidone-co-vinyl acetate) copolymer, poly(acrylic acid) (PAA), and poly(vinyl alcohol) (PVA)-co-albumin copolymer for the nanodelivery of the Sorafenib drug have been reported [19].Polyurethane (PU)-DOX nanoparticles were prepared in water through electrostatic interactions between amphiphilic PU and carboxyl pending groups (PU-COOH and DOX HCl).…”

Surface Modified Multifunctional and Stimuli Responsive Nanoparticles for Drug Targeting: Current Status and Uses

“…Temperature- and pH-responsive nanoparticles of biocompatible polyurethanes were found suitable for doxorubicin delivery [ 312 ] whereas polyesterurethane (PU) based nanoparticles (NPs) containing indomethacin were embedded in a scaffold so as to be applied as a local delivery system [ 313 ]. Moreover, some authors suggested that amino-functionalization of biodegradable polyester- and polyester/ether-urethanes (PURs) NPs can actively recognize target cells [ 314 ].…”

Preparation and performance study of a reactive polyurethane hot-melt adhesive/CS–Fe3O4 magnetic nanocomposite film/fabric

“…22,23 At present, PUR is being widely used in many elds, such as railway transportation, 24 automobiles, 25 book binding, 26 wood processing, 27 and fabric lamination, 28 because of its advantages of high bonding strength, a wide range of performance tuning, easy construction, a high solid content, and environmental protection. 29,30 Appropriate surface modication of nanoparticles can improve their interfacial interaction and compatibility with the polymer matrix. Thus, there have been several studies on the preparation of PUR/Fe 3 O 4 magnetic nanocomposites.…”