The present work investigates the potentiality of poly(N-vinyl caprolactam) (PVCL)-based thermoresponsive microgels decorated with cationic polymer brushes as drug delivery carriers. The effect of physico-chemical features of the colloids on cell viability response have to be carefully investigated to establish the range of suitable hydrodynamic diameters, crosslinking densities, lengths and ratios of the cationic polyelectrolyte shell which allow their efficient and effective use for cargo loading, transport and delivery. The colloidal stability of all cationic thermoresponsive microgels is maintained over several days of incubation at 37 °C in biological mimicking medium (Dulbecco's Modified Eagle's Medium supplemented with fetal bovine serum). The thin cationic polymer shell covalently anchored does not hinder the all range of microgels to be biocompatible while the higher cytotoxicity of the doxorubicin-loaded microgels on HeLa cells proves their anti-tumor activity. The core-shell PVCL drug delivery nanocarriers allow a sustained release of doxorubicin with a slightly higher viability of HeLa cells incubated in the presence of DOXO-loaded microgels compared to the free DOXO. The nature of the endocytosis pathway is investigated through a quantification of the extent of the cellular survival rate in the presence of various cellular uptake inhibitors. A clathrin-dependent internalization was observed.