We developed a pH/glutathione (GSH) dual-responsive smart nano-drug delivery system to achieve targeted release of a chemotherapeutic drug at breast tumor site. Doxorubicin (DOX) was linked to polyethylene glycol (PEG) through cis-aconitic anhydride (CA) and disulfide bonds (SS) to obtain the PEG-SS-CA-DOX prodrug, which spontaneously assembled into nanomicelles with a particle size of 48 +/- 0.45 nm. PEG-SS-CA-DOX micelles achieved an efficient and rapid release of DOX under dual stimulation by weak acidic pH and high GSH content of tumors, with the release amount reaching 88.0% within 48 h. Cellular uptake experiments demonstrated that PEG-SS-CA-DOX micelles could efficiently transport DOX into cells and rapidly release it in the tumor microenvironment. In addition, in vivo antitumor experiments showed that PEG-SS-CA-DOX had a high inhibition rate of 70% against 4T1 breast cancer cells along with good biosafety. In conclusion, dual-responsive smart nanomicelles can achieve tumor-targeted drug delivery and specific drug release, thus improving therapeutic efficacy of drugs.
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