A micellar cisplatin prodrug simultaneously eliminates both cancer cells and cancer stem cells in lung cancer

Platinum-based chemotherapy as first-line treatment for lung cancers encounters insufficient selectivity, severe side effects and drug resistance in clinics. In this study, we developed an amphiphilic prodrug of cisplatin-poly(ethylene glycol)-block-polycaprolactone and demonstrated that the prodrug formed micellar nanoparticles, NP_Pt(IV), with an average diameter of ∼100 nm. NP_Pt(IV) released platinum in response to the intracellular acidic and reductive environment, and in turn induced significant anti-proliferative activity in lung cancer cells. More importantly, NP_Pt(IV) exhibited a prominent inhibitory effect on CD133⁺ lung cancer stem cells (CSCs) and suppressed tumor growth in vivo. Unlike cisplatin treatment which eventually enriches CSCs, NP_Pt(IV) treatment prevents the accumulation of CD133⁺ lung CSCs in tumors. Therefore, NP_Pt(IV) simutaneously targeting CSCs and non-CSCs might represent a superior strategy to improve conventional anticancer therapy directed predominantly to tumor bulk populations.