Novel Nanomaterials For NIR-Ⅱ Fluorescence Imaging Guided Tumor Phototherapy

As cancer is the world’s leading fatal disease,countries are studying accurate imaging technology and effective treatment options for cancer,imaging technology as a key part of the field of cancer treatment,compared with traditional optical imaging technology,near-infrared window(NIR,700-1700 nm)imaging has clearer imaging effect.In particular,NIR-Ⅱ,1000-1700 nm)imaging has the advantages of high resolution,deeper tissue penetration depth and minimal self-tissue fluorescence,and has a wide application prospect in clinical medicine.In addition,compared with traditional cancer treatment methods,phototherapy technology has more obvious advantages,among which photodynamic therapy(PDT)and photothermal therapy(PTT)are the most representative phototherapy technology,which has the characteristics of small tissue damage and strong tumor inhibition,and has been widely concerned by researchers.The combination of near-infrared secondary imaging,photodynamic therapy and photothermal therapy can compensate for each other’s shortcomings and achieve better treatment results.Based on this,this paper constructs three new nanomaterials,which have deep imaging penetration,excellent imaging quality,good biocompatibility and good tumor suppression effect,and are applied to the diagnosis and treatment of tumors combined with NIR-Ⅱ IMAGING/PTT/PDT,and the specific research content is as follows:(1)Research and application of phototherapy reagents of NIR-Ⅱ nanomaterials based on DPP polymers: An organic fluorescent material DCT based on DPP derivatives was synthesized,and nanoparticle DCT NPs were prepared by nanoco-precipitation with F127 and DCT.Its basic physical properties and optical properties were characterized,including particle size,absorbance,fluorescence quantum yield,etc.Among them,DCT NPs have a particle size of about 105 nm,which can smoothly enter tumor cells.Its main absorption/emission peak is 721 nm/1084 nm,and it has a good extinction coefficient of 16.18 L/(g*cm).At the same time,it has excellent photothermal conversion efficiency(37.8%)and singlet oxygen yield(0.98%,with ICG as standard)under808nm laser irradiation,so it can be used as a nanomaterial for PTT/PDT combination therapy.DCT NPs have low biotoxicity and good biocompatibility,as well as good enrichment ability at tumors,and achieve the elimination effect of integrated tumor diagnosis and treatment.In summary,DCT NPs are expected to be a novel NIR-Ⅱ nano-organic material for the combined diagnosis and treatment of PTT/PDT tumors.(2)High-stability photothermal agent for the construction of tumor diagnosis and treatment platform under NIR-Ⅱ guidance: Based on the optical tunability of organic materials,a new NIR-Ⅱ nano-organic material O-BT NPs was designed,with a main absorption/emission peak of 845nm/1056 nm,an excellent extinction coefficient of 3.65×104 L/(mol*cm),and a fluorescence quantum yield of(0.35%).At the same time,the photothermal efficiency of O-BT NPs is 41.2%,and the nanomaterials show excellent stability in the photothermal cycle test,which can be used as photothermal agents for PTT therapy.In cell experiments and in vitro and in vivo imaging and experiments,it was shown that the material had good biocompatibility,as well as a cancer cell killing rate of nearly 90%,and O-BT NPs were injected into tumor-bearing mice for 30 h to achieve maximum enrichment at the tumor and achieve precise tumor positioning.This study provides new ideas for NIR-Ⅱ-guided tumor photothermal diagnosis and treatment.(3)Construction of high-stability photothermal agent based on NIR-Ⅱb imaging guidance:Based on the modifiability of organic materials,it is combined with rare earth materials and assembled into Se-TC@RENP@F under F127 wrapping,which has good photostability and particle size stability.Its main absorption/emission peak is at 978 nm/1545 nm,and fluorescence emission reaches the NIR-Ⅱb region.Under the excitation of 1064 nm laser,it shows good photothermal performance and photothermal stability,and the photothermal conversion efficiency is 36.9%.Through cell experiments,we can find that the material has high biosafety and a significant killing rate(about 85%)against He La cells under light.In conclusion,Se-TC@RENP@F provides a new scheme for NIR-Ⅱb-guided tumor photothermal therapy.