Platinated BODIPY Nanoparticles For Photoinduced Tumor Ablation

The photo-therapeutic drugs have attracted an extensive attention around the world because that phototherapy of cancer is a new way of clinical treatment.We usually name photodynamic therapy drugs as photosensitizer,and it has a hundred years of development history.Photosensitizers are divided by it's chemical structure and composition:(1)porphyrins,such as Photofrin I,ALA,etc.;(2)Chlorophyll,such as cyanine,chlorin,etc.;(3)dyes,such as phthalocyanine,fluoroboron dipyridamole and so on.At present,in addition to improveing the traditional photosensitizer's water solubility,light stability,safety,more work focused on the development of a variety of functional photosensitizer including it's tumor targeting,compatibility,absorption capacity of near-infrared light.The combination of photodynamic therapy and photothermal therapy is a novel therapeutic strategy.As the absorption of molecular oxygen in the deep of tumor can be promoted by photothermal effect of tumor,photosensitizers combined with photodynamic therapy and photothermal therapy can overcome the oxygen dependence in a certain extent.At the same time,the assistance of photothermal effect is advantage to better transportation and uptake in the tumor for drugs.In this paper,platinated fluorophore(boron dipyrromethene)core has been synthesized to fabricate self-assembled Bodiplatin-NPs.The aim was to improve the efficiency of interphase utilization according to heavy atom effect,which possess both enhanced singlet-to-triplet transition and nonradiative decay through their spin-orbit coupling and unoccupied dx2-y2 orbitals under light irradiation.Bodiplatin-NPs generate both abundant singlet oxygen and effective photothermal conversion upon light irradiation.Our proof-ofconcept design of self-assembled nanostructure with platinated fluorophore core represents a general and versatile approach for photoinduced tumor ablation.Chapter 1: Recent research progresses and therapies of tumor diseases,as well as the development of photosensitizers are briefly introduced and reviewed.Besides,further virious types of platinum complexes designed recently in detail and systematically,witch are the theories for our research.Chapter 2: The Platinated fluorophore(boron dipyrromethene)core was designed and synthesized,and micellar nanoparticles(Bodiplatin-NPs)were prepared by self-assembly.The structure of Bodiplatin-NPs was characterized,which indicated that the particle size was small and the dispersibility was good.After a series of photophysical properties of Bodipy,Bodiplatin and Bodiplatin-NPs,it was shown that platinum ligand could significantly affect the transition mode of BODIPY photosensitizer,which greatly improved the interdeposites and nonradiative transitions.Chapter 3: To explore the photoinduced damage of Bodiplatin-NPs against cancer cells.Including the uptake and localization of cells,the ROS generation and disruption of Bodiplatin-NPs in the cells,and the preliminary study on the toxicity and apoptosis to the tumor cells.It is proved that the platinum-based nanoparticles can generate severe synergistic photocytotoxicity for damaging tumor cells.Chapter 4: To demonstrate the anticancer efficacy in vivo with photodynamic therapy combined with photothermal therapy.Experiments show that Bodiplatin-NPs has a good anti-tumor effect with the combination of therapyfor photoinduced tumor ablation.And the safety and side effects of drugs were investigated and found that the drug has a high safety,so there is a certain clinical application prospects.Chapter 4: To further investigated the applicability of Bodiplatin-NPs at a clinically applied irradiation density,we evaluated their in vitro or in vivo antitumor effect under 0.15 W cm-2 irradiation Experimental results show that Bodiplatin-NPs still exhibited remarkable cytotoxicity and tumor inhibition effect.