Design Of Multi-Functional Photon-Activated Theranostics For Biomedical Applications

Over the world,cancer has been considered as one of the biggest threats for human health today and has placed heavy burdens on nowadays society.Photodynamic therapy(PDT),a new type of photon-initiated treatment modility which is different from traditional cancer treatments(e.g.surgery,radiotherapy,chemotherapy,etc.),has garnered tremendous popularity in personalized medicine,and gradually becomes a promising therapeutic approach for cancers by taking advantages of its spatiotemporal selectivity,reproducible applications without drug resistance,as well as noninvasive manner.However,traditional photosensitizers often suffer form several "Achilles' heels",such as strong oxygen dependence,poor tumor targeting,and limited treatment depth,as a result,severely limiting the wide application of PDT in clinical practice.Therefore,how to design high-performance phototherapeutic agents has been the concerned hotspot for researchers in biomedicine and chemistry.To surmount the intractable issue of strong oxygen dependence,herein,a type I PDT mechanism-based near-infrared light-triggered molecular superoxide radical(O2-·)generator(ENBS-B)is designed,and its detailed photosensitization principle as well as the O2-·-mediated "disregarding hypoxia" mechanism underlying the antihypoxia effect are also confirmed by using the paramagnetic resonance,fluorescence probe,and cell labeled imaging technologies.In addition,benifiting from the covalent conjugation with the cancer biomarker biotin,ENBS-B enbales to effectively distinguish the cancer cells from normal cells in the in vitro co-culture model.Based on these merits,ENBOS successfully realizes the efficient targeting growth inhibition of hypoxic tumors in vivo after irradiation.In order to improve the recognition ability towards tumors and the photodynamic antitumor efficiency of photosensitizers,here,a tactic for constructing "structure-inherent targeting" phototherapeutics is developed by using Forster resonance energy transfer(FRET)theory to introduce the rhodamine chromophore.Notably,this approach can not only significantly broaden the absorption spectrum and enhance the singlet oxygen generation potency of photosensitizers,but also successfully endow them with excellent native tumor targeting and enrichment ability.Thus,just exposure to a relative low light irradiation,the resultant photosensitizers can rapidly induce cell apoptosis,and the photodynamic antitumor effect both in vivo and in vitro are improved in orders of magnitude.In view of the limited treatment depth,herein,an approach by using FRET theory to enhance the NIR absorbance and photon utility of photosensitzier is proposed.In this way,the resultant photosensitizer enables to be more easily photon-activated in deep tissues,thereby dramatically augumenting the PDT efficiency against large or deep-seated tumors.Along this line,a photon-initiated structure-inherent targeting O2-· generator(ENBOS)with amplification effect is designed and prepared,as such,successfully realizing the substantially intensified selective ablation of deep-seated hypoxic tumors.Importantly,ENBOS can "light up" and distinguish the tumors from its surrounding tissues with a relatively high signal-to-backgroud ratio,which thus greatly improves the precision of photodynamic therapy on tumors and reduces the photosensitization side effects on normal tissues.