Biomimetic nanotherapeutics based on oxygen supply and ultrasmall Cu-Se-Au alloy nanoparticles for boosting radio-photothermal ablation of breast cancer

Radiotherapy (RT) is one of the important tools for clinical treatment of breast cancer. Currently, some nanoradiosensitizers have been developed for augmenting the therapeutic efficiency of RT. However, some limitations still exist for their further applications, such as oxygen dependence in hypoxic tumors, nonideal selectivity for tumors, and inevasible damages to normal tissues. To resolve these problems, a biomimetic nanoplatform was developed for efficient co-loading and precise co-delivery of oxygen and nanoradiosensitizer by taking advantage of large pore volumes and easy surface modification of dendritic large pore mesoporous silica nanoparticles (DLMSNs). The outer surfaces of DLMSNs were modified with citric acid for attaching firmly and chelating stably with ultrasmall Cu-Se-Au alloy nanoparticles possessing distinct radiosensitizing and photothermal conversion performances. The inner surfaces of DLMSNs were modified with perfluorosilane for loading perfluorohexane that has extraordinary oxygen-carrying capability to alleviate tumor hypoxia. White blood cells membranes were wrapped onto the surfaces of the resultant DLMSNs for promoting co-delivery of therapeutic agents targeting to tumor and reducing injuries to normal tissues. Biomimetic nanotherapeutic system thus prepared showed powerful suppression effects against breast cancer both in vitro and in vivo by intelligently integrating tumor-targeted delivery, oxygen supply, radiosensitizing and photothermal ablation.