Fragmented polymer nanotubes from sonication-induced scission with a thermo-responsive gating system for anti-cancer drug delivery

Abstract

Uniform purified long polymer nanotubes with crosslinked poly(glycidyl methacrylate) as the backbone and a pendant poly(N-isopropyl acrylamide) layer attached to the inner surface as a thermo-responsive gating system were synthesized by a two-fold “grafting-from” strategy inside cylindrical alumina nanopores. To adapt such long polymer nanotubes to be efficient nanocarriers for the intracellular delivery of anti-cancer drugs, a sonication-induced scission method was used to ‘cut’ the long nanotubes into short fragments. The discontinuous volume transition property in response to the temperature change for the pendant poly(N-isopropyl acrylamide) layer inside the nanotubes results in a reversible ‘closing/opening’ gating mechanism to control loaded drug release from the nanotubes. Using doxorubicin (DOX) as a model drug, in vitro thermo-responsive drug release behaviour and the related kinetics were studied in detail. The pristine fragmented polymer nanotubes were found to have good biocompatibility in the test with KB-3-1 cancer cells although toxic in their monomeric forms. More importantly, cell toxicity assays for DOX-loaded fragmented polymer nanotubes presented excellent temperature and concentration-dependent cytotoxicity with a low IC₅₀ of 1.4 μmol L⁻¹. These results indicated that such polymer nanotubes with a thermo-responsive gating system have potential as effective anti-cancer drug delivery vehicles.