Thermo-responsive and shape transformable amphiphilic scaffolds for loading and delivering anticancer drugs

Shape transformable carriers are an important class of biomaterials for selective drug delivery in a cancer tissue physiological environment. Here, we report the first example of an in situ shape transformable thermo-responsive amphiphilic scaffold for loading and delivering anticancer drugs at the cancer tissue temperature. New amphiphiles having a hydrogen bonded amide linkage that connects hydrophilic oligoethylene glycol with the hydrophobic renewable resource 3-pendadecylphenol were tailor made through multi-step organic synthesis. These amphiphiles underwent reversible self-assembly from three dimensional core-shell to rod-like structures in water (or PBS at pH = 7.4). The temperature-induced shape transformation was attributed to the lower critical solution temperature (LCST) and the process was confirmed by light scattering studies, electron microscopy, atomic force microscopy, variable temperature NMR and single crystal structure study. Anticancer drugs such as doxorubicin (DOX) and camptothecin (CPT) were successfully loaded in the core-shell structure without altering the shape transformation ability of the scaffold. In vitro drug release studies revealed that the DOX loaded scaffolds showed a selective release of more than 90% of the drug at the cancer tissue temperature (40-43 °C) compared to normal body temperature (37 °C, <10%). The drug kinetics study revealed that the release of DOX at the cancer tissue temperature followed a non-Fickian diffusion process. Thus, the present investigation provides the first insight into the development of in situ shape transforming thermo-responsive scaffolds and also establishes the proof-of-concept of their loading and delivering capabilities at the cancer tissue temperature.