The Application And Evaluation Of SDT In Prostate Cancer And Benign Prostatic Hyperplasia

Objective:To synthesize new high bio-compatible light and sound-sensitive integrated molecular probes by using photodynamic therapy as control,we clarified the killing effect of sonodynamic therapy in vitro,and explored acoustic-dynamic therapy for both prostate cancer and benign prostatic hyperplasia in vivo.And we found a new method for the treatment of prostate diseases such as CRPC and BPH with high efficiency for deep tissue penetration and good clinical application prospects.Methods:?1?Usinghumanalbuminproteinastemplate,anovel albumin-protoporphyrin IX?HSA-PPIX?was synthesized and verified as a molecular probe for integration of light and sound sensitivity,and both the physical properties and chemical properties of the probe were characterized.The singlet oxygen yield of HSA-PPIX under different irradiation conditions?laser and ultrasound?was measured and compared.?2?We used HSA-PPIX as light,acoustic sensitive probe and PC3 cells,C42 cells,LNCaP cells,MB49 cells,KYSE140 cells,and BPH1 cells were used for photodynamic and acoustic therapy.PDT treatment was used as a control to investigate the killing effect of different ultrasound irradiation on different cell lines.3)We established mouse model of prostate cancer xenografts.After intratumoral injection of PPIX,SDT treatment was performed to compare the changes and characteristics of prostate tumors before and after the treatment and to explore the feasibility of SDT therapy for the treatment of prostate cancer.?4?We established 12 rats model for prostatic hyperplasia.Under the ultrasound monitoring,rats with prostatic hyperplasia were injected with PPIX,and the SDT was treated by direct ultrasonic irradiation in vitro to explore the feasibility and therapeutic effect of SDT for the treatment of benign prostatic hyperplasia.Results:?1?In this study,a light,sonic and sensitive molecular probe HSA-PPIX with ultra-small,water-soluble and biocompatible properties was successfully established.By detecting the singlet oxygen yield after laser and sonication treatment,both excited states can produce singlet oxygen,wherein the photoexcited singlet oxygen yield is 49%,and the ultrasonically excited singlet oxygen yield is 35%.2)HSA-PPIX can be used as a light and sound sensitive agent to kill different tumor cells,prostate cancer cells and normal prostatic hyperplasia cells.Ultrasound irradiation for 2 minutes,ultrasonic intensity of 1W/cm^2,distance of 0.5cm,the maximum tumor cells killing rate was 23%,and laser irradiation with 2 minutes irradiation time,energy 10J/cm²,irradiation distance of 0.5cm,the maximum tumor cells killing rate was 18.7%compared with ultrasound irradiation.However,SDT can achieve cell killing effect at relatively long distances and barriers,and under the same conditions,the efficiency of laser is significantly reduced.?3?This study successfully constructed a subcutaneous implanted tumor model of PC3 cells?prostate cancer cells?.In the group of 3 tumor-bearing mice,the tumor inhibition rate was 37.1%in the SDT-treated group compared with the control group by direct injection of PPIX into the tumor.?4?In this study,12 rat models of benign prostatic hyperplasia were successfully constructed.After directly injecting PPIX into the prostate twice?interval 2 weeks?,ultrasound examination for the rat prostate was performed every 5 days,and the prostate volume change was observed continuously.The results showed that the prostate volume of the rat model decreased linearly.After 30 days of treatment,the rat prostate specimen volume was 0.84 ml and the weight was 0.82 g.Pathological examination of rat prostate specimens showed that there was a large piece of pyknosis and necrosis in prostate tissue after direct SDT treatment.Conclusion:?1?In this study,we successfully synthesized a novel optical and acoustic-sensitive integrated molecular probe HSA-PPIX,which effectively solved the problem of water solubility and bio-blending of its classic light and sensitizer PPIX.2)This study confirms the feasibility of acoustic-dynamic therapy for the treatment of CRPC,which HSA the unique advantages of long-distance excitation and deep tissue penetration.3)This study was the first to use SDT therapy for BPH therapy.