Studies On Magnetic Targeted Photodynamic Therapy And The Anti-Tumor Mechanism Of Purpurin-H

Photodynamic therapy(PDT)is a non-invasive treatment that involves the accumulation of a photosensitizing agent in solid tumors followed by the localized delivery of light of the correct wavelength to cause activation of the photosensitizer(PS),which,in the presence of oxygen,leads to the in situ generation of reactive oxygen species(ROS)that cause damage to cellular components and,ultimately,necrosis or apoptosis.However,PDT therapy agents, named photosensitizer(PS),have been compromised by the prolonged cutaneous photo-sensitivity,poor water-solubility and inadequate selectivity,which also hamper the clinical application of numerous traditional chemicals.Magnetic drug delivery system and novel photosensitizers are promising approaches to these problems.Magnetic nanoparticle(MNP)is comprised of magnetic core and shell material. Magnetic core can provide magnetic responsibility and magnetic targeting ability and the shell material can improve the biocompatibility and watersolubility without compromising their magnetic targeting.Novel photosensitizer is expected to possess good PDT effects and be excited by far-red light,which is less absorbed by tissue and made a good penetration.In this study,A serials of magnetic drug delivery system was developed and test by MTT assay to determine a nontoxicity and efficient carrier for photosensitizer.In vitro and in vivo distribution of the MNPs were monitored by magnetic resonance imaging(MRI).The PDT effects in vivo was evaluated by the xenograted nude mice.9,12-lmino-2,21-metheno-7,4:15,17-dinitrilo-4H-pyrido[4,3-b] azacyclonondecine-16-propanoic acid,10-ethenyl-5-ethyl-1,15,16,18,18,20-hexhydro-19-(hexamethylene)-6,11,15,22-tetramethyl-18,20-dioxo-,(15S,16S)-(9CI)is a novel chlorine photosensitizer,which shows good quantum yields of triplet state formation and singlet oxygen generation.As the maximal absorption wavelength of Purpurin-H is 690 nm,the laser beam can penetrate more deeply into tissues than the 630 nm laser used for ALA-PDT. Therefore,Purpurin-H could be a more effective second-generation PDT photosensitizer,with perhaps greater therapeutic usefulness particularly in more invasive skin tumors.In this study, the PDT effects and mechanism of Purpurin-H was investigated.As a result,magnetic chitosan nanoparticle(CS-pMNPs)were the one without toxicity and compromising the PDT effects of PHPP.The preparation of CS-pMNPs were then optimized and tested in vivo.It was showed that CS-pMNPs could be used in MRI monitored targeting PDT with excellent imaging and targeting ability.In addition nontoxicity and high photodynamic efficacy were verified both in vitro and in vivo.Most importantly,localization of nanoparticles in skin and hepatic tissue was under the threshold of detection of MRI, demonstrating avoidance of photosensitivity and hepatotoxicity.Furthermore,no photosensitivity was observed in all of nude mice injected with CS-pMNPs.Purpurin-H induces apoptosis of SW480 colon cells.Moreover,significant tumor regression is induced by PDT with Purpurin-H as photosentizer both in vitro and in vivo, indicating that Purpurin-H possess good PDT effects.Compared to the NC cells grafted mice, KD cells xenografts possess a relatively low growth rate,illustrating that KD cells is more sensitive to PDT,consistent to the result of in vitro.After all,it is evident that Purpurin-H was more appropriate as photosensitizer to resolve the circumventing resistance due to loss of DNA mismatch repair.