A pH-responsive polymer-coated CaO2 as oxygen-generating nanoparticle in situ for enhanced chemo-photodynamic synergistic therapy against tumors

Photodynamic therapy (PDT) has emerged as an efficient strategy for tumor treatment. However, Insufficient amounts of inherent hypoxia and intrinsic hydrogen peroxide (H2O2) in the tumor microenvironment severely constrained PDT, as oxygen is the critical substrate for photosensitivity reaction. Here, a pH-responsive H2O2 and O-2 self-supplying hybrid nanoparticle was designed. Through, the calcium peroxide (CaO2) as carriers loading a chemotherapeutic drug a photosensitizer 5,10,15,20-tetrakis(4-aminophenyl) porphyrin (TAPP) and doxorubicin (DOX), was covered with polyacrylic acid (PAA) to build up a feature material DOX-TAPP-CaO2@OA@PAA (denoted as DTCOP) through the reverse microemulsion method. In the acidic tumor microenvironment conditions exposing the water-sensitive CaO2 nanocore to generate hydrogen peroxide (H2O2) and O-2, the self-supplied O-2 alleviates hypoxia to enhance the PDT, and releasing DOX and TAPP. Synthetic characterization shows that the succeeded synthesized Nanocarriers could effectively carry DOX and TAPP to the tumor site and release O-2 at the low pH of TME. And the experimental results demonstrated that this interpose exogenous oxygen strategy is efficient at inhibition of tumor growth both in vitro and in vivo. The nanocomposite exhibits excellent biocompatibility and the ability to inhibit tumor growth and has significant potential for the treatment of hypoxic tumors.

Automated summary

Photodynamic therapy (PDT) is an efficient strategy for tumor treatment, but insufficient oxygen and hydrogen peroxide (H2O2) in the tumor microenvironment limit its effectiveness. This study designed a pH-responsive H2O2 and O-2 self-supplying hybrid nanoparticle, which could release oxygen (O-2) to alleviate hypoxia and enhance PDT in the acidic tumor microenvironment. The nanocomposite effectively delivered chemotherapeutic drug doxorubicin (DOX) and photosensitizer 5,10,15,20-tetrakis(4-aminophenyl) porphyrin (TAPP) to the tumor site and demonstrated efficient inhibition of tumor growth both in vitro and in vivo.