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Most chemotherapy agents have serious side effects due to lack of tumor targeting, which affects their clinical application. In addition, as an essential characteristic of malignant tumor, hypoxia is attracting exclusive research focus regarding its non-invasive real-time tracing in novel targeting delivery system. Herein, we designed a mixed micelle with tumor targeting and hypoxia responsiveness for tumor therapy and imaging. In particular, the dual-modified mix micelles were self-assembled by folic acid (FA) and 2-(2-nitroimidazole) ethylamine (NI) conjugated polymers, in which paclitaxel (PTX) and quantum dots (QDs) were co-loaded into the hydrophobic core. The drug loaded micelles showed satisfactory drug encapsulation, good storage stability, and sustained release properties. In vitro cell experiments showed that the mixed micelles exhibited enhanced cytotoxic effect and improved the cellular uptake, especially under hypoxic conditions, which was due to the FA mediated active targeting effect and NI induced hypoxic responsive release. In vivo experiments further proved that the mixed micelles possessed outstanding tumor targeting and hypoxia responsive properties. Furthermore, the drug loaded micelles showed excellent anti-tumor effect and can realize real-time in vivo imaging. This work demonstrates that the dual-modified mixed micelles co-loading with PTX and QDs might provide a novel approach for tumor therapy and imaging. |
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