Fabrication Of Novel BODIPY Self-assembly For Cancer Combined Therapy

The boron-dipyrrole-methene dye(BODIPY,BDP)and their derivatives,being a new class of organic fluorescent dyes,have aroused wide attentions in the field of light-induced tumor therapy because of high molar extinction coefficient,excellent stability to chemical and light,relatively insensitive to the polarity as well as pH and reasonably stable to physiological conditions.In this thesis,we have fabricated two kinds of BODIPY-based self-assembles for the cancer combination treatment,especially for hypoxic tumor treatment.The main works are as following:1.A new anti-tumor drug,diiodo-distyryl-TEG-borondipyrromethene(TBDP),was designed.The introduction of diethylamine reduces the fluorescence quantum yield of TBDP,and triethylene glycol monomethyl ether(TEG)can improve the water solubility and facilitate the assembly of TBDP to form stable nanoparticles(TBDP NPs).Experiments showed that TBDP NPs could be internalized by cells,and it would simultaneously generate both singlet oxygen and heat to kill the cells by 635 nm irradiation.The animal study results further confirm it could inhibit the growth of tumor,proving the combination of photothermal/photodynamic therapy can enhance tumor inhibition rate.2.A novel near-infrared distyryl-diethylamine-borodipyrromethene nanoparticle(NBDP NPs)was synthesized by conjuncting near-infrared photothermal agent BODIPY with free radical generator AIBI,which could self-assemble into water-soluble nanoparticles NBDP NPs.The BODIPY unit acts as an alkyl radical initiator for its high photothermal conversion efficiency(54%).Under the irradiation of 808 nm,NBDP NPs can generate heat and simultaneously induce the release of oxygen-independent alkyl radical,solving the problem of unsatisfactory photodynamic therapy effect due to hypoxia in the tumor site.The experiments have proved alkyl radical generated from NBDP NPs in hypoxic condition could induce apoptosis and inhibit the growth of tumor.This combination of photothermal therapy with free radical outlines a new platform for hypoxic cancer therapy.