Photosensitizers/photothermal Agents-loaded Injectable Hydrogels For Cancer Phototherapy

Because of their unique and unreplaceable merits in medicine,during the past few decades,hydrogel,a novel polymeric material,is receiving increasing attention.The development of new optical diagnosis and treatment concepts significantly promotes the biomedical applications of injectable hydrogels.This thesis focuses on the fabrication of photosensitizers-and photothermal agents-containing injectable hydrogel systems and their applications in cancer theranostics.Moreover,the influences of the injectable hydrogel on the singlet oxygen generation efficiency of photosensitizers and the photothermal conversion efficiency of photothermal agents were investigated.The injectable hydrogel was prepared by using the Schiff base linkages formed between the amine groups of glycol chitosan and the aldehyde groups of dibenzaldehyde-terminated telechelic poly(ethylene glycol)(or termed as dialdehyde-functionalized PEG,DF-PEG).Specifically,this thesis includes the following three chapters:1.TMPyP-loaded injectable hydrogel for cancer photodynamic therapy.The injectable hydrogel was prepared by mixing 1.5 wt%glycol chitosan and 1 wt%DF-PEG.The formed hydrogel was characterized by scanning electron microscopy(SEM),fourier transform infrared spectroscopy(FTIR),and rheometry.Herein,meso-tetrakis(1-methylpyr-idinium-4-yl)porphyrin(TMPyP)was selected as a model of water-soluble PSs and encapsulated into the injectable hydrogel.The UV-vis absorption and fluorescence emission spectra of TMPyP in phosphate-buffered saline(PBS)and in hydrogel showed that the two samples exhibited similar spectral patterns with peaks locating at similar wavelengths.However,at the same concentration,the fluorescence emission intensity and singlet oxygen(1O2)generation of TMPyP in hydrogel showed an almost 2-fold increase as compared with that of TMPyP in PBS.Furthermore,for other common PSs,we have also confirmed that these PSs have stronger PL emission and higher 1O2 generation in hydrogel than in PBS.This phenomenon may be caused by the high viscosity of the hydrogel medium.The three-dimensional structure of the hydrogel helps to stabilize TMPyP molecules within the hydrogel matrix,which reduces the rotation and intermolecular collision of the PS molecules,leading to the enhancement of FL intensity and ROS generation.2.RB-loaded injectable hydrogel for photosensitized inactivation of microorganisms.Herein,rose bengal(RB)was selected as a model of water-soluble PSs and encapsulated into the injectable hydrogel.We found that at the same concentration,the fluorescence emission intensity and singlet oxygen(1O2)generation of RB in hydrogel increased remarkably as compared with that of RB in PBS.The final 1O2 yield of RB-loaded hydrogel was more than three times higher than that of free RB solution.Additionally,RB-loaded injectable hydrogel presented a prolonged functional 1O2 generation time.The system can keep efficiently desirable drug concentration and targeted for effective PDT treatment,having a medicine significance and potential application in the field of anti-inflammatory biomemitic film.3.AuNRs-loaded injectable hydrogel for cancer photothermal therapy.We have compared the photothermal conversion efficiency of PEG-AuNRs in PBS and hydrogel.The results showed that a higher PEG-AuNRs concentration led to a faster temperature increase.Besides,at the same concentration of PEG-AuNRs,the photothermal conversion efficiency of PEG-AuNRs in hydrogel was higher than that of PEG-AuNRs in PBS.NIR photoexcitation of PEG-AuNRs-loaded injectable hydrogel led to remarkable cell death and tumor inhibition,confirming its potential for photothermal therapy.Apart from AuNRs,other photothermal agents-loaded injectable hydrogels also exhibited an intenser NIR absorbance peak and a higher photothermal conversion efficiency as compared with the corresponding aqueous solution systems.