Construction Of Photoactivatable Fluorescent Probes And Their Theranostic Applications

Photoactivatable fluorescent probes have recently shown great potential in the acquisition of biochemical information and have been widely used in the fields of bio-imaging,bio-sensing and theranostics.Light irradiation with advantages of high spatio-temporal resolution,bioorthogonality and easy operability has become an ideal stimulus in biological study.Howeover,most of current photoactivatable fluorescent probes suffer from drawbacks in terms of low photoactivation efficiency,toxic by-products,and complicated synthesis.To tackle these challenges,a series of photoactivatable fluorescent probes were constructed based on photooxidation reaction.Based on a thorough study of their photophysical and photochemical properties and photoactivation mechanisms,these probes were applied for bio-imaging and cancer theranostics.The detailed contents and results are as follows:(1)Chemotherapy is one of the common cancer treatment methods,but chemotherapy usually suffers from serious side-effects due to the off-target toxicity,which restricts its clinical application.Therefore,it’s highly desirable for selective activation of chemotherapy with efficient reducing of side effects.The photoactivation strategy is especially suitable for treatment of shallow-seated tumors to in situ activate prodrugs,which can efficiently improve the targeted therapy efficiency.Based on our previous researches on photoactivatable cancer theranostics,we proposed a biorthogonal photocatalytic strategy for cancer treatment with biogenic riboflavin as the photocatalyst for in situ oxidation of the non-toxic prodrug dihydrochelerythrine(DHCHE)into anticancer drug chelerythrine(CHE).The photocatalytic activation from DHCHE into CHE can be in situ monitored by green-to-red fluorescence conversion,which was applied to cancer cells killing and inhibition of tumor growth in vivo.The photocatalytic mechanism was also fully explored by means of density functional theory(DFT)calculations.We believe this imaging-guided bioorthogonal photo-catalytic activation strategy is promising for precise cancer therapy.(2)Fluorophores with long-wavelength emission has advantages of high tissue penetration ability and efficient avoiding of auto-fluorescence interference.To achieve long wavelength fluorescence emission,traditional electron closed-shell fluorophores usually require the decoration of large-sized conjugation units and electron donor-acceptor groups via tedious synthetic steps,which seriously restrict their applications.In contrast,radical cations with a low energy gap between ground and excited state has advantages of long-wavelength absorption,but most radical cations suffer from low emission efficiency and poor stability in aqueous solution,which restrict their application in bio-imaging.Herein,we found that the chemotherapeutic drug chlorambucil can generate fluorescent radical cation via photooxidation reaction,which can be used for monitoring of the distribution of chlorambucil inside cancer cells.This photoactivation strategy with ability of in situ generation of emissive radical cations is promising for study of drug activation mechanisms.Finally,we summarized the advantages of photoactivation fluorescence probes prepared in this thesis and provided an outlook for future bio-imaging and theranostic applications.