High Biocompatible Poly(lactic-co-glycolic acid)-Based Nanosensitizer With Magnetic Resonance Imaging Capacity for Tumor Targeted Microwave Hyperthermia and Chemotherapy.

Microwave (MW) hyperthermia has been widely studied in tumor therapy, while the lack of specificity, and the potential toxicity induced by instability or difficulty in degradation of existed MW thermal sensitizers still limits the application. Herein, a new biocompatible Poly(lactic-co-glycolic acid) (PLGA)-based nanosensitizer of Dtxl-Gd@PLGA-PEG-TPP (DGPPT) with capacities of magnetic resonance (MR) imaging and mitochondrial targeting for MW hyperthermia combined with chemotherapy was constructed via a double emulsion solvent evaporation method. The modified TPP significantly enhanced the specificity of sensitizer for targeting mitochondria, a heat-sensitive energy supply plant in cells. Thus the MW thermal damage induced by the loaded Gd in PLGA nanospheres was also strengthened. Together, the system could also achieve MR imaging due to the existence of Gd. In addition, the encapsulated Dtxl performed the chemotherapy of inhibiting mitochondrial function for assisting with MW hyperthermia. In vivo experiments demonstrated that PLGA had high biocompatibility that no obvious damage occurred even the dose was up to 200 mg/kg. Meanwhile, DGPPT+MW representing the combination of mitochondrial targeting and MW hyperthermia-chemotherapy has also been proved to shrink tumor size effectively. This study provides a new direction for building biosafe and multifunctional MW sensitizer with active targeting ability to impede tumor growth.

High Biocompatible ZIF-8 Coated by ZrO2 for Chemo-microwave Thermal Tumor Synergistic Therapy.

The zeolitic imidazolate framework-8 (ZIF-8) is a specifically promising drug carrier due to its excellent intrinsic properties. However, the high toxicity of ZIF-8 nanoparticles severely limits their further research and clinical application. In this work, the biocompatibility of ZIF-8 nanoparticles is greatly improved by coating ZrO2 onto the surface. The survival rate of cells and mice in the ZIF-8@ZrO2 nanocomposite group is significantly increased compared with the undecorated ZIF-8 nanoparticle group. Doxorubicin (DOX) as a chemotherapeutic drug is deposited during the ZIF-8 growth by a facile one-pot method. Ionic liquid (IL) is loaded into the pore of the ZIF-8/DOX@ZrO2 nanocomposites for enhancing microwave thermal therapy. The tumor inhibition rate of ZIF-8/DOX@ZrO2@IL nanocomposites with synergistic microwave thermal therapy and chemotherapy is obviously higher than in other groups. In addition, the ZIF-8/DOX@ZrO2@IL nanocomposites are used for real-time monitoring of the therapeutic outcomes due to the excellent computed tomography contrast agent, ZrO2. Therefore, such a ZrO2 coating strategy shows great promise for overcoming high toxicity of ZIF-8 nanoparticles, which offers a new platform for tumor synergistic microwave thermal therapy and chemotherapy using the ZIF-8/DOX@ZrO2@IL nanocomposite as a theranostic nanocarrier.