Design,Synthesis,and Application Of ¹⁹F MRI Traceable Functional Molecules

Cancer is the main cause of human death.Improving early diagnosis of tumors,developing non-invasive diagnostic tools,and implementing targeted therapy are vital for cancer treatment.Molecular imaging offers biological characteristics of tumors in a non-invasive way,which is of great value for early diagnosis,treatment,and prognosis of cancer.As a widely used imaging technique in clinical practice,magnetic resonance imaging（MRI）provides images without ionizing radiation and tissue depth limit.Nevertheless,traditional ¹H MRI suffers from high background signal and accumulated toxicity caused by contrast agents.In recent years,¹⁹F MRI has gained much attention as an increasingly important MRI technique because of the suitable properties of ¹⁹F nuclei,such as 100%natural abundance,the similar gyromagnetic ratio of ¹H,a high relative sensitivity that is 83%of ¹H,and no background interference.In this paper,we have designed and synthesized several ¹⁹F MRI traceable functional molecules,which can be prepared as nanocarriers to achieve multimodal imaging and synergistic therapy,thus providing new strategies for early diagnosis and treatment of tumors.Multifunctional and branched monodisperse oligopolyethylene glycol（M-OEG）can be applied as PEGylation agents,linkers,and scaffolds in biomedicine.However,the tedious synthesis limits their biomedical applications.We herein present an azides reductive dimerization method for the conveniently synthesizing of aza-M-OEGs and derivatives.With this method,we synthesized 30 aza-M-OEGs.One of the hexa-arm M-OEGs with 54 symmetrical fluorines,from which has excellent physical,chemical,and biological properties dendrimer was identified as high performance ¹⁹F MRI-traceable biomaterial.Photodynamic therapy（PDT）,as a new method for cancer treatment,has attracted extensive attention due to its non-invasive and space-time selectivity.Therefore,we have designed and synthesized an amphiphilic fluorinated macromolecule with the photosensitizer IR-780 as the core applying the developed reductive dimerization method.Compared with the IR-780,this compound has been greatly improved in solubility,fluorescence,photodynamic properties,etc.Based on the amphiphilic property of the compound,we designed and prepared monodisperse fluorinated drug-loaded microemulsions with high stability.The prepared microemulsions are endowed with dual-modal fluorescence and ¹⁹F MR imaging capability,as well as Chem-PDT dual therapeutic effects,which can facilitate early diagnosis and treatment of tumors.Owing to their high extinction coefficients,long absorption wavelengths,and modification tunable photophysical and photochemical properties,phthalocyanines have been widely used as photosensitizers for photodynamic therapy（PDT）.So we designed and synthesized an amphiphilic phthalocyanine.The phthalocyanine derivative has eight PEG chains,which significantly improves the water solubility of phthalocyanine.It contains 72 symmetrical fluorines,allowing ¹⁹F MRI at a low concentration.At the same time,it is easy to self-assemble in water by amphiphilic chains,increasing its tumor-targeting ability.In addition,it exhibited excellent PDT and photothermal therapy（PTT）efficiency.The results demonstrated that the phthalocyanine derivative could be used as a molecular theranostics.