Development of multi-layered and multi-sensitive polymeric nanocontainers for cancer therapy: in vitro evaluation

Nanoscale drug delivery systems represent a promising strategy to treat cancer and to overcome the side effects of chemotherapy. In particular, hollow polymeric nanocontainers have attracted great interest because of their structural and morphological advantages and the variety of polymers that can be used, allowing the synthesis of stimuli-responsive materials capable of responding to the biochemical alterations of the tumour microenvironment. Here are reported the synthesis, characterization and in vitro evaluation of a three-stimuli-sensitive hollow nanocontainer consisting of three different shells, each one sensitive to a specific tumoral stimulus: in order pH, temperature and reducing environment. To test its properties, daunorubicin was used as a model drug, for which the nanocontainers exhibited excellent encapsulation ability. The in vitro drug release behaviour was studied under different conditions, where the system proved capable of responding to the selected tumoral stimuli by releasing a larger amount of drug than in physiological environment. The hollow system itself showed negligible cytotoxicity but the loaded nanocontainers and free drug showed identical cytotoxicity and intracellular localization. Therefore, this formulation can be considered as a promising platform to develop an injectable delivery system capable of improving systematic toxicity without affecting or reducing the activity of the encapsulated drug.