A Smart Tumor-microenvironment Responsive Nanoprobe for Highly Selective and Efficient Combination Therapy
Therapeutic effects of chemotherapy and photodynamic therapy (PDT) are limited seriously by tumor hypoxia and low cells uptake capacity. Herein, a smart tumor-microenvironment (TME) responsive nanoprobe was developed using pH-responsive and bio-resolvable CeOx/Fe2O3 as a carrier not only for strengthening cells uptake capacity, increasing drug packaging efficiency and modulating tumor hypoxic, but also as an acceptor of the Förster resonance energy transfer (FRET) to achieve energy quenching of excited photosensitizer. With the urchin-like hollow structures of the CeOx/Fe2O3, chemotherapy drug doxorubicin (DOX) and photosensitizer chlorine e6 (Ce6) could be co-loaded to the CeOx/Fe2O3 carrier to form the nanoprobe (CeOx/Fe2O3-C&D). In normal tissue, the nanoprobe CeOx/Fe2O3-C&D showed weak cytotoxicity. Once into the TME, CeOx/Fe2O3 nanoshells began to break up, DOX was released rapidly at the tumor site, CeOx/Fe2O3 as catalase-like to decompose endogenous H2O2 and produce O2 persistently to overcome hypoxic in situ, meanwhile the Ce6 could be transformed from the “silent state” to the “activated state” to open the fluorescence signal and generate singlet oxygen (1O2) by weakening FRET efficiency. Therefore, our study showcases an innovatively strategy to enhance cells uptake capacity, adjust tumor hypoxia and achieve highly selective and specific combination therapy.