The enhanced chemotherapeutic effects of doxorubicin loaded PEG coated TiO2 nanocarriers in an orthotopic breast tumor bearing mouse model

Abstract

Many chemotherapeutics used for cancer treatments encounter issues during delivery to tumors in vivo and have high levels of systemic toxicity. One of the most prominent progresses in improving drug delivery efficiency is through exploring various types of nanoparticles (NPs) as drug carriers. Recent studies have demonstrated that titanium dioxide (TiO₂) nanocarriers have potential for drug delivery and therapy even in multidrug resistant cancers in vitro. Moreover, it was proved that the anticancer activity of doxorubicin (DOX) was enhanced by loading onto TiO₂ nanoparticles in breast cancer cells in vitro. However, there is no evidence from the animal model in vivo, which is a critical step for their further clinical applications. The aim of this study was to explore novel TiO₂–PEG–DOX nanoparticles, the DOX loaded polyethylene glycol (PEG) coated TiO₂ nanocarriers, and investigate their potential application in enabling controlled drug release and enhancing the chemotherapeutic efficacy of DOX in the orthotopic breast tumor bearing mice. The tumor growth and drug treatment efficacy were dynamically monitored by bioluminescence imaging (BLI), and the safety of NPs for in vivo usage was also evaluated. It was found that TiO₂–PEG–DOX nanoparticles possessed improved antitumor efficacy without observable side effects compared to the free DOX treatment. Our study suggested that the PEG coated TiO₂ nanocarrier is a safe and potential platform for the efficient drug delivery and minimizing the systemic toxicity of chemotherapeutic agents. It has been proved for the first time that TiO₂-based nanocarriers enhance the chemotherapeutic effects of doxorubicin in vivo.