Electromagnetic Field Responsive Multifunctional Hybrid For Cancer Multimodality Treatment

Cancer is the world leading cause of death.Surgery,radiotherapy and chemotherapy are most commonly used for cancer treatment in clinical.However,due to the side effect and limited efficacy of these methods,attention has been paid on the development of novel multifunctional hybrids for tumor theranostics.As a new emerging ajuvant alternative treatment method in clinical,hyperthermia or thermotherapy have attracted enourmous interest,such as magnetic hyperthermia,photothermal theray,radiofrequency and microwave ablation.To reduce side effect to adjacent normal tissues,electromagnetic field responsive hybrids are promising to target heat into tumor site.Moreover,the development of multifunctional platform combing thermotherapy and other treatment method is proved to be effective in clinical cancer therapy.Our study is focused on the development of themal agents generating heat under low frequency electromagnetic field.Hydrogel as the microwave sensitizer and gallium based liquid metal?LM?as the magnetic hyperthermia mediator are proposed,which provide an alternative agents for microwave ablation and magnetic hyperthermia.Three multifunctional platforms,Fe₃O₄ and doxorubicin loaded uniform alginate microsperes for tumor alation,PEGylated LM hybrids for breast cancer therapy and LM hydrogel for combined postsurgical treatment were developed.Except for the study of themogeneration effect,the feasibility of LM hybrids to be applied in alternating magnetic field and p H stimuli responsive delivery,radiotherapy sensitization and CT image was also investigated.Moreover,the characterization of as prepared hybrids,biocompatibility evaluation,in vitro cytotoxicity and in vivo anti-tumor efficacy under different treatment models were systematically evaluated.The results showed that alginate microspheres fabricated by emulsification are proved to be an effective microwave sensitizer,which promoted local treatment temperature and made the heat distributed more uniformly.Combined with chemotherapy of anticancer drug,it can effectively ablate tumors.Meanwhile,due to the loading of Fe₃O₄,MRI imaging can be used to locate the microspheres,providing more effective guidance for hyperthermia.Non-magnetic gallium indium based liquid metal possessed heat generation ability under alternating magnetic field and can be used as a novel magnetic hyperthermia mediator.Drug loaded liquid metal hybrid had magnetic field and p H stimuli response release property and CT imaging enhancement characteristics.After injection into the tumor site,it can effectively treat breast cancer with the combined therapy of magnetic hyperthermia and chemotherapeutic drugs.The measurement of gel dosimetry and clonegenic assay demonstrated the feasibility of liquid metal as radiation sensitizer.Liquid metal hybrids prepared by combining with LM and self-healing hydrogel is applied for postsurgical implantation.Hyperthermia at the site of the tumor residue bed,combined with radiotherapy and chemotherapy,can effectively inhibit tumor recurrence.