Preparation And Antitumor Study Of Muscovite Nanosheets And Human Serum Albumin Nanoparticles

The complexity,diversity,and heterogeneity of tumors seriously undermine the therapeutic potential of treatment.Therefore,the trend in current clinical research has gradually shifted from a focus on monotherapy to combination therapy for enhanced treatment efficacy.More importantly,the cooperative enhancement interactions between several types of monotherapy contribute to the naissance of multimodal synergistic therapy,which results in remarkable superadditive(namely “1+1>2”)effects,stronger than any single therapy or their theoretical combination.In order to achieve the bimodal synergistic therapy of chemotherapy and immunotherapy,in Chapter 2,we constructed a two-dimensional doxorubicin loaded mica nanosheets(Dox@EM).Due to its two-dimensional morphological features,such as ultrathin thickness,ultrahigh specific surface area,easy functionalization and so on,2D inorganic nanosheets play an important role in effective cancer diagnosis and treatment,overcoming the inherent limitations of traditional treatment methods.Long-term toxicity and poor biocompatibility are the critical issues for most inorganic nanosheets,which hinder their further oncological applications and clinical translations.As the main component of traditional Chinese medicine,mica has the advantages of low long-term toxicity and good biocompatibility.Compared with free antitumor drugs,Dox@EM showed pH-responsive drug release and selective cytotoxicity,which is expected to reduce multi-drug resistance and systemic toxicity.Moreover,mica plays an important role in immunology and oncology,mainly promoting the polarization of RAW 264.7 cells into M1 antitumor type.In order to achieve the trimodal synergistic therapy of chemotherapy,photothermal therapy,and photodynamic therapy,in Chapter 3,we constructed a human serum albumin drug-loading system(HSA-ICG-PTX@HA).Human serum albumin(HSA),paclitaxel(PTX)and indocyanine green(ICG)would self-assemble into stable nanoparticles in aqueous solution by simple mixing,and then could be coated with hyaluronic acid(HA)by amidation reaction.In this system,HSA is a biocompatible carrier platform,PTX is an effective antitumor drug,ICG can serve as a fluorescent imaging probe and a photothermal agent,while HA is a ligand that activelytargets into cancer cells overexpressing CD44 and can be decomposited by hyaluronidase to trigger particle size reduce.Therefore,our work develops a biocompatible theranostic agent that is purely composed by FDA-approved agents,promising for future imaging-guided combination therapy of cancer.