Development And Applications Of Multimodal Phototheranostic Nanosystems

At present,optical technology has been widely used in modern medicine,and has played an important role in the diagnosis and treatment of various diseases.In the field of cancer diagnosis and treatment,optical technology also has unique advantages.Optical imaging has the advantages of high sensitivity,high temporal and spatial resolution,good safety and low cost,while phototherapy has the advantages of high spatial resolution,low side effects and good efficacy,which makes optical technology a good candidate in the field of cancer treatment.Despite the rapid development of optical therapy technology and its unique advantages,the efficacy of single phototherapy still has certain limitations,facing the problems of tumor recurrence and metastasis.In order to solve this problem,combining chemotherapy,immunotherapy,gene therapy and radiotherapy with phototherapy is a feasible method to improve the efficacy,which is also the focus of current research in this field.Based on optical diagnosis and treatment,this paper constructed two different nanotheranostic systems and studied different diagnosis and treatment platforms combining imaging and treatment methods.The specific research contents are as follows:（1）Iodine-rich Nanoadjuvants for CT Imaging-guided Photodynamic Immunotherapy of Breast Cancer.Immunotherapy stimulates body’s own immune system to kill cancer cells,herein,we report an iodine-rich nanoadjuvant（INA）for photo-immunotherapy.INA is prepared by encapsulating a toll-like receptor 7 agonist（R837）and a photosensitizer（phthalocyanine）into an iodine-rich amphiphilic copolymer PEG-PHEMA-I.By virtue of the enhanced permeation and retention（EPR）effect,INA can effectively accumulate into tumor site.Under light irradiation,PDT triggered by INA will induce immunogenic cell death（ICD）and R837 was leaded to the proliferation of effector T cells for immunotherapy.The photo-immunotherapy mediated by INA shows good anticancer efficacy both in vitro and in vivo.Meanwhile,INA is also a CT contrast agent owing to its high density of iodine,which can successfully light up tumor by CT imaging.Thus,our study develops a light triggered nanoadjuvant for CT imaging-guided enhanced photo-immunotherapy.（2）Capsaicin-decorated semiconducting polymer nanoparticles for light-controlled calcium-overload/photodynamic combination therapy.At this part,we design a capsaicin-decorated semiconducting polymer nanoparticles（CSPN）to modulate calcium ion channel of cancer cells for calcium-overload cancer therapy without adding additional calcium element.CSPN is composed of a near-infrared（NIR）absorbing semiconducting polymer（SP）PCPDTBT and a capsaicin-conjugated amphiphilic copolymer,PEG-PHEMA-Cap.Under NIR laser irradiation,PCPDTBT can generate singlet oxygen（¹O₂）,which not only trigger the release of capsaicin,but also induce PDT.The released capsaicin can further activate transient receptor potential cation channel subfamily V member 1（TRPV1）of U373 cancer cells,leading to influx of calcium ion into cells.In addition,the intense NIR-II fluorescence signal of CSPN makes it suitable for tumor imaging.Thus,our study develops a tumor specific nanotheranostic system for NIR-II fluorescence imaging-guided calcium-overload/PDT combination therapy.