Synthesis And Fluorescence Analysis Of Two Near-infrared Drug-loaded Probes

Cancer treatment is facing huge challenges in modern medical technology.Tumor treatment can improve the effect of drug treatment with minimal side effects through the non-specific distribution of small molecule drugs in the body.At present,many chemotherapeutic drugs have achieved clinical applications.Common drug release systems can be divided into several categories:storage drug release systems,matrix drug release systems,chemically-mediated drug release systems,and solvent-regulated drug release systems.These systems can further adjust the rate of drug absorption into the body by controlling the rate of drug release from the dosage form,so as to obtain better therapeutic effects.However,drugs have some side effects,including uncontrollable release of drugs into the body,effects on enzyme activities in the body after the drug is released,and side effects of drugs on changes in the microenvironment of the body.These side effects are closely related to the drug delivery system.Based on the above points,we carried out the following work:1.To control the drug release,we combined anticancer drugs with cyanine,and synthesized a near-infrared drug-functionalized fluorescent probe based on photoactivation,2-(E)-2-(E)-2-((4-(((4-(4-(bis(2-chloroethyl)amino)phenyl)butanoyl)o xy)methyl)-3-nitrobenzoyl)oxy)-3-(2-((E)-1-ethyl-3,3-dimethylindolin-2-ylidene)ethy lidene)cyclohex-1-en-1-yl)vinyl)-1-ethyl-3,3-dimethyl-3H-indol-1-ium(CPC).Compared with free drugs,this combination shows better controllability in vivo.Interestingly,after the drug is released,a new probe is generated.CPD can be stabilized for at least 20 minutes in the intracellular photostability time.The probe CPD can also continuously and specifically detect the changes of Cys and H₂S in organisms,with the 20 times of enhanced fluorescence intensity.CPC realizes light-controlled drug release during drug delivery and visual detection of intracellular biothiols.The fluorescence emission of the probe is between 700-800nm,and its near-infrared characteristic is beneficial to in vivo imaging.The development of CPC will help us in-depth study the changes in the cellular environment caused by anti-cancer drugs.2.For carboxylesterase mediated drug delivery in cancer cells,we designed a prodrug probeforcarboxylesteraseresponse2-(E)-2-(E)-2-((4-(4-(bis(2-chloroethyl)amino)phenyl)butanoyl)oxy)-3-(2-((E)-1-ethyl-3,3-dimethylindolin-2-ylid ene)ethylidene)cyclohex-1-en-1-yl)vinyl)-1-ethyl-3,3-dimethyl-3H-indol-1-ium (CYC).The probe has the functions of both detecting carboxylesterase and releasing the dru.Interestingly,after the drug release,the product can respond to the internal p H.It is expected that there will be a good application prospect in detecting the changes in the intracellular environment caused by the metabolism of carboxylesterase.