Entropically driven controlled release of paclitaxel from poly(2-ethyl-2-oxazoline) coated maghemite nanostructures for magnetically guided cancer therapy

Abstract

Theranostic nanostructures serve a dual purpose of therapy and diagnosis. A major fraction of these are based on polymer coated magnetic nanostructures of iron oxides (magnetite and maghemite), owing to the efficient drug loading capacity of polymer shells and enhanced magnetic contrast effects of the iron oxide core. In the current work we are proposing poly(2-ethyl-2-oxazoline) coated linear thermoresponsive nanostructures of maghemite (γ-FeO) for potential application in targeted cancer therapy. The polymer coating was obtained via a modified sol-gel technique based on entropically driven phase separation of poly(2-ethyl-2-oxazoline) above its cloud point (CP) temperature of 63 °C in water. The developed nanostructures were further loaded with paclitaxel, a polar anticancer compound at room temperature (25 °C). The entropically driven release of paclitaxel at various concentrations and physiological temperatures was modeled and their application to the PC3 prostrate cancer cell line was investigated by treating in vitro. The steering efficiency of the magnetic nanostructures during their navigation through large blood vessels was also analyzed with the help of a synthetic model of the human axillary artery. The proposed application of these newly developed nanostructures can easily be extended towards localized delivery of additional polar anticancer drugs like cisplatin and doxorubicin.

Designing the Surface Chemistry of Inorganic Nanocrystals for Cancer Imaging and Therapy

“…For example, NPs coated with poly(2-ethyl-2-oxazoline), PEtOx, show the same minimal level of nonspecific protein adsorption and cellular uptake as with PEG, making them a promising candidate for clinical applications [167]. Peptoid poly(oxazoline) and poly(sarcosine) ligands have been developed to coat iron oxide NPs, gold NPs and QDs [168][169][170][171][172][173][174][175]. For example, IONPs coated with PEtOx and loaded with paclitaxel have been proposed for magnetically guided cancer therapy [170].…”

“…Peptoid poly(oxazoline) and poly(sarcosine) ligands have been developed to coat iron oxide NPs, gold NPs and QDs [168][169][170][171][172][173][174][175]. For example, IONPs coated with PEtOx and loaded with paclitaxel have been proposed for magnetically guided cancer therapy [170]. In another example, gold nanorods coated with PEtOx and loaded with doxorubicin were evaluated in vitro for combined chemo and photothermal cancer therapy [171].…”

Recent Progress of Paclitaxel Delivery Systems: Covalent and Noncovalent Approaches

“…In addition to liposomes, micelles, and hydrogels, other carriers such as chitosan‐based microspheres, [ 93,116 ] poly(amidoamine) dendrimer, [ 117–119 ] PEG‐capsaicin, [ 120 ] heparin, [ 121 ] nanofibers, [ 122,123 ] peptides, [ 124 ] denatured bovine serum albumin, [ 125 ] poly(ε‐caprolactone) (PCL), [ 126 ] or incorporating superparamagnetic iron‐oxide nanoparticles to render magnetic targeted delivery [ 127–129 ] have been investigated to deliver PTX. Interestingly, Wang et al.…”

“…Under the same principle, internal lumen materials halloysites [ 229 ] were also used for PTX delivery. In addition, functional inorganic substrates such as magnetic nanoparticles can enable magnetically guided cancer therapy [ 129 ] and hyperthermia, [ 230 ] or quantum dots to develop simultaneous therapy and diagnosis. [ 231 ]…”

Theranostics Based on Magnetic Nanoparticles and Polymers: Intelligent Design for Efficient Diagnostics and Therapy

“…Kumar et al studied magnetic navigation steering capabilities of the nanostructures formed by maghemite NPs and thermoresponsive poly(2-ethyl-2oxazoline) in a synthetic blood vessel model (Kumar et al, 2018). High efficiency of magnetic steering navigation was achieved for all directions of blood flow studied, including angular, parallel, and antiparallel flow to the target destination combined with efficient release of anticancer drug (paclitaxel) at 41 • C. Delavari et al and Herranz-Blanco et al also reported targeted delivery to tumor sites via magnetic guidance which allowed for increased DOX uptake in cancer cells (Herranz-Blanco et al, 2016;Delavari et al, 2019).…”