| Current process of photodynamic therapy used in clinical trial is very slow.And it meets three main problems.First,unsatisfied propertises of PSs should be modified,including singlet oxyen or ROS generation quantum yield,tumor-tagerting,bio-compatibility and metabolization for post-treatment;Second,high hypxia at the tumoe site;Third,the main abosorption of PSs,which limits their application in deep penetration PDT.Based on that,we design and prepare four different photo theranostic system and try to solve the problems that are met in clinical PDT,including preparing two different systems for PAI-guided photodynamic/photothermal cancer therapy,FAP technology-based BRET mediated tumor ablation and synthesizing different MG2I analogs to improve the singler oxygen generation quantum yield of FAP-MG2I and their applications in tumor cells killing and mitochandrio damage1.Near-infared absorbing WSCP dots as photo acoustic agents for synergetic cancer treatmentFirst,we synthesize a new kind of water-soluble conjugated polymers(WSCPs)and make them to form nanoparticles through self-assembly to get WSCP dots.The optical spectrum confirms that WSCP dots can not generate fluorescence with 730 nm laser irradiation,but can generate photoacoustic(PA)signal.Further PAI in vivo shows that WSCP dots can accumulate at the tumor site most after injecting WSCP dots into mice for 4h.More importantly,with 730 nm laser irradiation,WSCP dots can not only generate singlet oxygen(Quantum yield=13%),but also can generate heat(photothermal conversion efficiency=54%),which can inhibit the tumor growth both in vitro and in vivo.Therefore,WSCP dots can be used for PAI-guided photodynamic/photothermal cancer therapy,which shows great potential in clinical application2.AC6o nanoparticles as photo theranostic agents for synergetic cancer treatmentConsidering that the main absorption of C60 is in UV-Vis,we proposed the energy transfer strategy to solve this problem by conjugating NIR-absorbing antenna on the surface of C60.And the energy absorbed by antenna can be transferred into C60 to generate singlet oxygen more effectively.More interestingly,C60 nanoparticles can not only generate singlet oxygen,but also can generate heat after encapsulated by amphiphilic molecules,DSPE-mPEG.Therefore,C60 NPs can be used as photo theranostic agnets for synergetic cancer treatment3.Genetically BRET meadiated PDT based on FAP technologyWe conducted BRET mediated singlet oxygen generation and tumor ablation based on FAP-MG complex.The BRET ratio showed that the energy generated from bioluminescence can be effectively transferred into FAP-MG complex,which can futher generate singlet oxygen and do tumor cells killing.Further bacterial experiment and cell experiment confim that,this BRET mediated SOG system can kill the bacterial and inhibit tumor growth very effectively,which provides a new idea for deep pentration PDT4.Synthesis of MG2I analogs and their study in tumor ablation and mitrochandira damageWe synthesized a series of MG2I analogs,including MG2I-ester、MG2I-ester-R、MG2I-PT、MG2I-NH3CI MG2I-SO3-、MG2I-COO-.The singlet oxygen quantum yield result(SOG QY)confirmed that their abilities for singler oxygen generation are quite different after binding with dL5**，especially for MG2I-SO3-and MG2I-COO-(25.2%and 26.2%,respectively)while MG2I-ester is only 13%.Kd measurement showed that the lower the Kd is,the higher SOG QY is,which means the higher binding affinity will be good for singlet oxygen generation for MG2I-dL5**complex.Further cell viability analysis demonstrated that MG2I-COO-can inhibited tumor cell growth the most effectively,which is consistant with its SOG QY More interestingly,different MG2I showed different oxygen consumption rate inside the mitrochandria,among which MG2I-COO-consumed the most.Cell viability analysis and mitochondria damage can further confirm that,the higher binding between MG2I analogs and dL5**can result in the higher cell killing efficiency and more oxygen consumption in cellular mitochondria. |
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