The Construction Of ESIPT Based Fluorophores And Their Application In Theranostics

Based on the advantages of large Stokes shift and excellent photostability,Excited-state intramolecular proton transfer（ESIPT）fluorophores have been widely applied in biomedical research.ESIPT fluorophores like 2-（2-hydroxyphenyl）-benzothiazole,salicylaldehyde azine with the introduction of"photoactive"groups like o-nitrobenzyl or enzyme response groups have been applied for photo-triggered cell imaging and specific detection of biological enzyme activity.Although ESIPT fluorophores have been widely applied in biological imaging and detection,the ESIPT fluorophores applied in theranostics combined with the abilities of“light up”imaging and disease treatment require further research.Based on ESIPT fluorophores 2-（2-hydroxyphenyl）-benzothiazole and salicylaldehyde,we herein developed photo-triggered Zn²⁺release system for regulation of zinc enzyme activity and fluorophores that activate immunogen cell death by inducing endoplasmic reticulum stress in order to achieve the integrated function of diagnosis and treatment.The specific research contents are as followings:（1）A photo-triggered Zn²⁺release system named HBTH-Zn-TAT nanoparticles（NPs）was designed and synthesized using ESIPT fluorophore 2-（2-hydroxyphenyl）-benzothiazolines（HBTH）as the Zn²⁺ligand,amphiphilic polymers as the matrix,and TAT peptide as the cell penetrating ligand.The nanoparticles can quickly release Zn²⁺under light irradiation.We futher applied the NPs to the regulation of extra-and intracellular zinc enzyme activities.（2）Based on salicylaldehyde derivatives,we developed ESIPT fluorophore CA-Cbl that can quickly enter cells and light-up the endoplasmic reticulum.It can generate ROS with high efficiency within 10 minutes and cause endoplasmic reticulum oxidative stress.At the same time,it can increase cell permeability.It is found that CA-Cbl can be used as a chemotherapeutic drug to effectively induce the expression of damage associated molecular patterns of immunogenic cell death,including calreticulin exposed on the surface of tumor cells（ecto-CRT）,release of high mobility group protein B1（HMGB1）and adenosine triphosphate（ATP）.As a new type II chemotherapeutic drug that induces immunogenic cell death,CA-Cbl is expected to be used in the preparation of cancer vaccines.