Abstract
Physiological calcification of the treated tumor area is considered to be a predictor of good prognosis. Promoting tumor calcification by inducing mitochondrial metabolic disorder and destroying calcium equilibrium has a potential inhibitory effect on tumor proliferation. Here, by promoting calcification by inducing mitochondrial dysfunction combined with triggering a surge of reactive oxygen species, we construct a bioresponsive calcification initiator, termed CaP-AA, using CaHPO(4) covalently doped l-ascorbic acid. CaHPO(4) releases Ca(2+) within the cytoplasm of tumor cells to trigger calcium overload. Meanwhile, exogenous l-ascorbic acid indirectly enhances metabolic balance disruption via pro-oxidant effects. Such Ca(2+) overload increases the likelihood of tumor calcification in vivo for tumor inhibition by perturbing mitochondrial homeostasis. The introduction of responsive calcium sources that would, in turn, trigger intratumoral calcification mediated by perturbing mitochondrial homeostasis would be an effective regulatory strategy for tumor therapy.