Design,Synthesis And Cancer Therapy Study Of Water-soluble Metallic Iridium Complexes

In recent years,Photodynamic therapy（PDT）has been regarded as a new therapeutic approach for cancer because of its non-invasive properties,spatiotemporal controllability and low systemic toxicity.The key element of PDT is the construction of efficient photosensitizer（PS）.However,traditional PSs are commonly hydrophobic and tend to aggregate in aqueous media due to their rigid structures and strongπ-πstacking effect,which lead to aggregation-caused quenching（ACQ）of emission and reduced ¹O₂ generation.Recently,considerable effort has been focused on the fabrication of nanoparticles（NPs）by introducing amphiphilic polymers or nanocarriers to enhance the solubility.More importantly they are still extremely unavailing for ACQ PSs,which severely limit their clinical applications.Moreover,cancer therapy with a single therapy may cause many problems and shortcomings,such as multiple drug resistance（MDR）,which reduces the accumulation of the antitumor chemotherapy drug in tumor cells and subsequently produces a poor therapeutic outcome.Hence,it is necessary and meaningful to design a simple and effective strategy to construct multifunctional NPs and successfully overcome the undesired ACQ effect and hydrophobicity,as well as apply multi-modal therapy in cancer treatment.In this paper,we designed and synthesized a series of red-emitting water-soluble metal iridium complexes as PSs for phototherapy.To improve the water solubility biocompatibility in different ways by modifying the auxiliary ligands of PSs,which successfully overcomes the ACQ effect and realizes multi-modal therapy in tumor cells.The relative works are as follows:（1）Two iridium complexes（1-H and 2-H）were prepared with carboxylic acid as an auxiliary ligand.The better biocompatibility,stronger absorption,higher ¹O₂ generation ability and spherical NPs（1-Na and 2-Na）with small size were synthesized via a simple and easy reaction and used in PDT as phosphorescent PSs,exhibiting excellent performance in PDT and tumor cells imaging.The ACQ effect,hydrophobicity and low loading efficiency of traditional PSs were successfully overcome through a facile and convenient way.This study provides a facile and practical method to design biocompatible and effective PSs for potential clinical applications.（2）Specifically,the novel iridium complex Ir-PTX was designed and synthesized by combining the PTX acted as the anti-cancer drug with photoactive precursor iridium complexes for its high intersystem crossing（ISC）ability.The corresponding NPs（Ir-PTX NPs）were obtained by self-assembly methods without any pre-modification step or nontherapeutic carriers,and realized multi-modal synergistic therapy in cells.This method significantly improves the water solubility and poor permeability of PTX and effectively quantifies the content of each component.The as-prepared Ir-PTX NPs showed rapid enzyme responsive dissociation to release PTX and metal iridium complexes,which induced the ACQ effect of iridium complexes,enhanced the ¹O₂ production capacity and realized the combined chemo-phototherapy,achieving the synergistic effect of“1+1>2”.This work provides a broad prospect in the design and preparation of multi-functional and high-efficiency nanomedicine for multi-modal cancer treatment.