Mesoporous calcium peroxide-ignited NO generation for amplifying photothermal immunotherapy of breast cancer

L-arginine (LA) as a semiessential amino acid within human body has shown great promise in cancer therapy since it can continuously generate nitric oxide (NO) in the presence of inducible NO synthase (iNOS) or reactive oxygen species (ROS). However, NO production efficiency in tumor tissue is severely restricted by the hypoxic and H2O2-deficient tumor microenvironment (TME). Herein, mesoporous calcium peroxide (CaO2) with the ability of supplying O2/H2O2 has been prepared to encapsulate and oxidize LA to achieve controllable local release of NO in the acidic TME. Interestingly, the generated NO can aggravate the abnormal retention of Ca2+ in cells, thus resulting in amplified oxidative stress and immunogenic cell death. To improve the stability of CaO2 in the body fluid, polydopamine (PDA) is further introduced to coat on the surface of LA-CaO2 and its high photothermal conversion property will reinforce the immunogenic dying of tumor cells. Such a NO-enhanced phototherapeutic nanoplatform, LA-CaO2@PDA, exhibit the most effective treatment in inhibiting primary and distant tumor growth and suppressing lung metastasis of 4T1 tumor by provoking a strong antitumor immune response.