Construction Of Near-infrared Photoactivated Semiconductor Polymer Nanocomposites For Cancer Combined Immunotherapy And Multimodal Imaging

There are more and more treatments for cancer,but a single treatment can not achieve the ideal effect.Therefore,in this research,we comprehensively applied a variety of therapeutic means,and made use of the advantages of treatment and imaging to improve the therapeutic effect of cancer to a higher level.By integrating different methods together,two treatment strategies were proposed respectively,which were Project 1 and Project 2.The specific research contents were shown in Chapter 2 and Chapter 3.In Project 1 we report the development of radioactive semiconducting polymer nanoparticles（r SPNs）for multimodal cancer theranostics.Such r SPNs constructed through labeling poly（ethylene glycol）（PEG）grafted SPNs with iodine-131(¹³¹I)exhibit ideal photothermal property,excellent singlet oxygen（¹O₂）generating ability and good radiolabeling stability.Owing to their small particle dimension and PEG surface corona,r SPNs show an effective accumulation into subcutaneous tumors of living mice after systemic administration.The good fluorescence property and stable radiolabeling of r SPNs enable contrast signals for near-infrared（NIR）fluorescence and single photon emission computed tomography（SPECT）dual-model imaging of tumors.Moreover,r SPNs provide combinational action of photothermal therapy（PTT）,photodynamic therapy（PDT）and radiotherapy under NIR laser irradiation,resulting in much higher therapeutic efficacy in inhibiting tumor growth and metastasis relative to SPNs-mediated treatment.This study thus offers a multifunctional organic nanosystem for multimodal cancer theranostics.Cancer metabolic programs play important roles in restricting various anticancer therapies.Although metabolism interventions using inhibitors can provide an alternative way for cancer treatment,the un-controlled bioactivity and accumulation of inhibitors often lead to limited therapeutic efficacy and off-target side effects.To address these concerns,In Project 2 we herein develop semiconducting polymer nanocomplexes(SPN_CN)that can specifically inhibit autophagy and immunometabolism in tumor microenvironment upon near-infrared（NIR）photoactivation for enhanced cancer immunotherapy.Such SPN_CN consist of a semi-conducting polymer nanoparticle as the core and singlet oxygen（¹O₂）-responsive shell with the encapsulations of chloroquine（CQ）and NLG919 as the autophagy and immunometabolism inhibitor,respectively.SPNCN upon NIR photoactivation generate ¹O₂ to exert photodynamic therapy（PDT）for killing tumor cells and inducing immunogenic cell death（ICD）,and the produced ¹O₂ effectively destroys the ¹O₂-responsive shells to achieve precise release of CQ and NLG919 in the tumor microenvironment.CQ inhibits autophagy to amplify PDT effect and ICD,and NLG919 intervenes immunosuppressive tryptophan（Trp）metabolism,synergistically improving the antitumor immunity.Therefore,SPN_CN-mediated enhanced therapy can inhibit the growth of tumors in bilateral melanoma-bearing mouse models.This work offers a smart polymer platform to integrate the bispecific metabolism interventions with cancer therapy in a safe and effective manner.