pH-Responsive Selenium Nanoplatform for Highly Efficient Cancer Starvation Therapy by Atorvastatin Delivery

Recently, starvation-inducing nutrient deprivation has been regarded as a promising strategy for tumor suppression. As a first-line lipid-lowering drug, atorvastatin (ATV) significantly reduces caloric intake, suggesting its potential in starvation therapy for suppressing tumors. Accordingly, we developed a novel starvation therapy agent (HA-Se-ATV) in this study to suppress tumor growth by using hyaluronic acid (HA)-conjugated chitosan polymer-coated nano-selenium (Se) for loading ATV. HA-Se-ATV targets cancer cells, following which it effectively accumulates in the tumor tissue. The HA-Se-ATV nanoplatform was then activated by inducing a weakly acidic tumor microenvironment and subsequently releasing ATV. ATV and Se synergistically downregulate the levels of cellular adenosine triphosphate while inhibiting the expression of thioredoxin reductase 1. Consequently, the starvation–stress reaction of cancer cells is significantly elevated, leading to cancer cell death. Furthermore, the in vivo results indicate that HA-Se-ATV effectively suppresses tumor growth with a low level of toxicity, demonstrating its great potential for clinical translation.