Targeted Delivery Of CO To Mitochondria Enhances The Photodynamic Anti-tumor Effect Of PCN-224

Photodynamic therapy（PDT）has received widespread attention due to its low side effects and high selectivity.However,the three major elements（light,oxygen,and photosensitizer）constituting PDT have limited the wide application of PDT to a certain extent.With the development of nanomedicine and nanotechnology,researchers have made considerable progress and breakthroughs in these three areas.However,a single PDT therapy still cannot satisfy the clinically complex physiological process.Combining PDT therapy with other therapies（photothermal therapy,chemotherapy,immunotherapy,gene therapy,etc.）in order to achieve the purpose of synergistic treatment of tumors has become an increasingly popular research.Gas therapy has become an emerging"green therapy"because it uses signal molecules（NO,H₂S,and CO）from the human body to treat tumors.Among them,CO has a"two-sided"feature:CO slightly enhances the production ability of reactive oxygen species（ROS）of normal cell mitochondria,which plays an anti-apoptotic effect;and stimulates tumor cell mitochondria to produce a large amount of ROS,which plays a role in promoting apoptosis.The targeted delivery of CO-releasing moleculars（CORMs）to tumor tissues has become a common way to utilize CO,and different CORMs can release CO under different stimuli（heat,light,oxidant,etc.）,which makes it possible for the combination of gas therapy and other therapies.Among them,CORM-401 is a new type of water-soluble CORMs.Its production capacity of CO is three times that of commercially available CORM-3,and it can accelerate the release of CO under the action of oxidants.In response to the above problems,this thesis constructed a triphenylphosphine（TPP）-containing amphiphilic polymer encapsulated photosensitizer PCN-224 and metal carbonyl compound CORM-401 nanoparticles,which was designed to deliver the photosensitizer and CORM-401 to the mitochondria so that PDT and gas therapy can be used to synergistically treat tumors.A series of characterization results proved the successful preparation of nanoparticles;the results of confocal microscopy proved that TPP has the effect of targeting mitochondria and can target photosensitizers and CORM-401 to the mitochondria;the results of cytotoxicity proved the amphiphilic polymer had good biocompatibility,after encapsulating PCN-224 and CORM-401,it can combine PDT and gas therapy to treat tumors together.These results indicate that the system achieves mitochondrial targeted drug delivery,obtains a good cancer cell treatment effect,and provides an effective nanocarrier for the combination of PDT therapy and gas therapy.