Novel Organic Polymer Nanosystems For NIR-Ⅱ Fluorescence Imaging And Tumor Phototherapy Platform

Different from the traditional imaging diagnosis with low resolution,near-infrared window（NIR,700-1700 nm）fluorescence imaging can provide more intuitive,clear,real-time and dynamic images,especially the second near-infrared window（NIR-II,1000-1700 nm）fluorescence imaging,which can offer deeper penetration depth,higher spatial resolution and minimal tissue autofluorescence,and which is outstanding in the field of optical diagnosis of many major diseases.In addition,compared with the traditional tumor therapies with limited curative effect,the emerging tumor phototherapy in recent years has been proved to be one of the most promising therapies because of its minimal invasiveness,sensitivity,controllability and differential selection.Photothermal therapy（PTT）and photodynamic therapy（PDT）are two forms of tumor phototherapy.In view of the limitations of monotherapy,combinational therapies of NIR-II fluorescence imaging combinined with PTT and PDT can overcome the shortfalls of each other,obtain synergy or superposition effects and enhance the overall tumor therapeutic outcomes.The development of combinational phototherapy is inseparable from the construction of nanoplatforms with integrated diagnostic and therapeutic units.Nanomaterials based on organic conjugated polymers are widely used to enhance tumor imaging diagnosis and treatment because of their special molecular structure,superior absorption and emission,low biological toxicity and excellent stability of aqueous solution.On this basis,two nanotheranostic systems based on organic conjugated polymer materials are designed and applied to the tumor phototheranostic experiment of NIR-II fluorescence imaging combined with PTT and PDT.The specific research contents are as follows:（1）Construction and application of NIR-II nanoagent for phototherapy based on polymer of DPP derivativesAn organic conjugated polymer material P-D with fluorescence and based on DPP derivatives was synthesized,which has aggregation-induced emission（AIE）effect.Nanoparticle P-D NPs with excellent NIR-II emission were prepared by self assembly and nano coprecipitation method.The main absorption/emission peak of the nanoparticles was in 786 nm/1064 nm.It had high molar extinction coefficient(27.30 L·g^-1·cm^-1),high photothermal conversion efficiency（39.58%）and excellent light stability.P-D NPs could stimulate its NIR-II fluorescence imaging through a single NIR light source,and achieved the tumor phototherapy combined with PTT and PDT.In vitro cell experiments,it showed that the killing rate of the nanoparticles on tumor cells is about 80%,also,it had excellent biosafety,The vivo phototherapy experiment of mice within 15 days further verified its safety and tumor killing effect.By injecting P-D NPs through caudal vein,the fluorescence signal of systemic blood vessels in mice had been clearly observed for a long time.After 42 hours of material injection,the maximum enrichment can be achieved at the tumor to realize tumor localization and imaging diagnosis.This study provides a new strategy for the development of reusable and stable NIR-II nano phototherapy reagents.（2）Novel application of a polymer-based nanoparticle in NIR-II fluorescence imaging guided tumor phototherapy platformA novel NIR organic conjugated polymer material P-F with fluorescence was synthesized.Then,a polymer-based nanoparticle P-F NPs was prepared by self-assembly and simple and efficient nano coprecipitation method.Its main absorption/emission peak was in 645 nm/938 nm.Its NIR-II fluorescence imaging guided PDT/PTT tumor phototherapy effects can be triggered by a single NIR light.After systematic exploration,It showed that P-F NPs had good fluorescence quantum yield（0.34%）,singlet oxygen（¹O₂）yield up to 12.59%,superior fluorescence and photodynamic properties.In vitro cell experiments,It showed that the killing rate of the nanoparticles on tumor cells was about85%,also,it had excellent biocompatibility.By injecting P-F NPs through caudal vein,it was observed that the NIR-II fluorescence image of the tumor site of tumor bearing mice was significant,and the tumor localization could be realized.This work provides a new idea for constructing a new intelligent nano system for comprehensive therapy such as tumor phototherapy guided by NIR-II fluorescence imaging.