Search

The acquisition of multidrug resistance (MDR) is a major hurdle for the successful chemotherapy of tumors. Herein, a novel hybrid micelle with pH and near-infrared (NIR) light dual-responsive property is reported for reversing doxorubicin (DOX) resistance in breast cancer. The hybrid micelles are designed to integrate the pH- and NIR light-responsive property of an amphiphilic diblock polymer and the high DOX loading capacity of a polymeric prodrug into one single nanocomposite. At physiological condition (i.e., pH 7.4), the micelles form compact nanostructure with particle size around 30 nm to facilitate blood circulation and passive tumor targeting. Meanwhile, the micelles are quickly dissociated in weakly acidic environment (i.e., pH ≤ 6.2) to release DOX prodrug. When exposed to NIR laser irradiation, the hybrid micelles can trigger notable tumor penetration and cytosol release of DOX payload by inducing tunable hyperthermia effect. In combination with localized NIR laser irradiation, the hybrid micelles significantly inhibit the growth of DOX-resistant MCF-7/ADR breast cancer in an orthotopic tumor bearing mouse model. Taken together, this pH and NIR light-responsive micelles with hyperthermia-triggered tumor penetration and cytoplasm drug release can be an effective nanoplatform to combat cancer MDR. [ABSTRACT FROM AUTHOR]

Chemotherapy is an important approach for clinical cancer treatment. However, the success of chemotherapy is usually hindered by the occurrence of intrinsic or acquired multidrug resistance of cancer cells. Herein, we reported an effective approach to overcome doxorubicin (DOX) resistance in MCF-7/ADR breast cancer using DOX-loaded pH-responsive micelles. The micelles were prepared from a pH-responsive diblock copolymer, poly(ethylene glycol)-block-poly(2-(diisopropylamino)ethyl methacrylate) (PEG- b -PDPA), and a vitamin E derivate (D-α-tocopheryl polyethylene glycol 1000 succinate, TPGS) (denoted as PDPA/TPGS micelles). At neutral pH of 7.4, DOX was loaded into the hydrophobic core of PDPA/TPGS micelles via a film sonication method. After cellular uptake, the DOX payload was released in early endosomes by acidic pH-triggered micelle dissociation. Meanwhile, the TPGS component synergistically improved the cytotoxicity of DOX by targeting mitochondrial organelles and reducing the mitochondrial transmembrane potential. In vitro cell culture experiments using DOX-resistant MCF-7/ADR cells demonstrated that PDPA/TPGS micelles reduced the IC 50 of DOX by a sixfold magnitude. In vivo animal studies showed that DOX-loaded PDPA/TPGS micelles (PDPA/TPGS@DOX) inhibited tumor growth more efficiently than free DOX in a nude mouse model bearing orthotopic MCF-7/ADR tumor. All these results imply that the mitochondria-targeted pH-responsive PDPA/TPGS micelles have significant potential for efficiently combating DOX resistance in breast cancer cells. [ABSTRACT FROM AUTHOR]

On page 2489 H. Yu, Y. Li, and co‐workers report a pH and near‐infrared light responsive micelle for combating cancer multidrug resistance (MDR). The micelles induce moderate hyperthermia effect upon NIR laser illumination to facilitate their tumor penetration and lysosome escape, thus improving the therapeutic efficacy of doxorubicin. This study implies a novel strategy for treatment of MDR cancer. [ABSTRACT FROM AUTHOR]