Construction And Application Of Combined Therapy System Based On Porphyin

Cancer,as a major threat to human health today,has received widespread attention from researchers.A variety of new treatment methods continue to emerge with their advantage and disadvantage.With the depth of research,combined therapy has become the main direction of current research,because of the combination of treatment methods can improve the treatment effect and avoid the shortcomings in single treatment(such as chemotherapy resistance).In this paper,based on the photosensitizer tetraphenylporphyrin and biocompatible polymer,a series of combination therapy platforms include photodynamic-chemotherapy and photodynamic-gene were designed and synthesized.Mainly includes the following three aspects:(1)Fe-tetraphenylporphyrin(Fe-TPP)modified polyethylene glycol(PEG)and histidine(His)modified polylactic acid(PLA)were synthesized.Through the coordination of metal porphyrins and histidine,we prepare pH-responsive metal complex micelles which loaded anti-cancer drugs doxorubicin(DOX)to achieve the combination of chemotherapy and photodynamic therapy.The structure of TPP-PEG and PLA-His segments was confirmed by 1H NMR and IR;the metal coordination and photodynamic effects were proved by UV-vis spectroscopy.TEM,dynamic light scattering(DLS),critical micelle concentration(CMC)and in vitro drug release simulation showed that the pH response of the metal complex micelles was measured.Under the neutral condition(pH = 7.4),the micelles can self-assemble the DOX.In the acidic environment(pH = 5.3),the coordination effect of the metal is weakened,which leads to the disintegration of the micelles and the release of DOX.Finally,the cell survival test proved the combination of chemotherapy and photodynamic therapy.The metal coordination micelle as a combination of photodynamic and chemotherapy carrier platform has a good effect.(2)In the study of the above system,it was found that the coordination effect of Fe and histidine was not ideal.Considering the steric hindrance effect,we selected the more flexible Histidine-modified polycaprolactone(PCL-His)as the hydrophobic side while retaining Fe-TPP-PEG as hydrophilic and photodynamic effects try to construct more efficient photodynamic-chemotherapy combination drug delivery platform.1H NMR and UV-vis sepectroscopy proof the successfully synthesis.The results of TEM,DLS,CMC and in vitro drug experiments show that the pH response of the micelles,flow and confocal data demonstrate the ability of micelles to deliver to the drug,Finally,MTT assay was used to test the inhibitory effect of drug-loaded micelles on cancer cells and to show the combination of the treatments for the improvement of therapeutic effect.(3)Gene therapy is also a new type of cancer treatment like photodynamic therapy,the combination of gene and PDT is our new attempt.Through the electrostatic interaction between PLL and DNA and the host-guest recognition of β-CD and TPP,we successfully construct complex DNA nanoparticles as a combined platform for gene therapy and photodynamic therapy.The β-CD-PLL and TPP-PEG structures were identified by 1H NMR.The transfection experiments demonstrated the excellent transfection ability of the DNA nanoparticles.Flow cytometry and confocal showed that DNA endocytosis was promoted.Apoptosis experiments demonstrated that genes and photodynamic treatment co-induces apoptosis in cancer cells.