Preliminary Study Of The Mobile Application And Arsenic Nanosheets For Diagnosis And Treatment Of Prostate Cancer

Part ? Development of mobile application for dynamic monitoring the risk of prostate cancer and clinicopathology Objectives: To develop an application dynamically monitoring the prostate cancer(PCa)risk for patients to assess their own progression of PCa risk at home.Methods: Between January 2010 and December 2019,all of the 1,697 patients underwent trans-rectal ultrasound prostate biopsy at the cancer center,which is one of the Chinese Prostate Cancer Consortium.Patients' clinical parameters from January2010 to May 2018 were used to establish models that consisted of several risk factors with P value <0.1 in univariate analysis and with P value <0.05 in multivariate analysis(n=1113),including model 1(predicting PCa),model 2(predicting PCa with high Gleason scores(7 or higher))and model 3(predicting PCa with the high clinical stage(T2b or higher)).Other Patients from June 2018 to December 2019 were used to validate models(n=440).Patients with the lack of sufficient data were eventually excluded(n=144)Results: A total of 1553 patients were involved in this study,andan application was used to performthe models.The predictive cut-off value and area under the curves(AUCs)of model 1,2 and 3 were respectively calculated(cut-off: 0.53,0.38 and 0.40,AUCs: 0.88,0.89 and 0.89).Using a cut-off value of 10%,three models obtained a high sensitivity(>95%).Besides,more patients can be correctly reclassified via our models(42.9 to 55.5%).Decision curve analyses revealed a decent net benefit in any probability for models.These results were well verified in the validation cohort.Conclusions: This application showed decent performance in predicting the risk of PCa and clinicopathology,which is available and convenient for patients to self-assess the progress of PCa risks so that being better to participate in disease management.Part ? PSMA-targeted arsenic nanosheets: a nanoplatform for prostate cancer therapy via ferroptotic cell death and ATM deficiency-triggered chemosensitizationBackgroud: Ferroptosis,a newly recognized non-apoptotic cell death form,has recently been introduced for effective cancer therapy.Methods: The reported ferroptosis-inducing nanomaterials mainly consisted of metal-based components.We used liquid exfoliation technique to generate AS nanosheets(ANs)from the simple substance arsenic.PEG and PSMA antibody(PSMAA)were adopted to modify ANs to acquire PEG-PSMAA-modified ANs(PMANs)for better water dispersibility,biocompatibility and tumor-targeting capacity.Subsequently,a proof-of-concept tumoricidal agent,DOX,was applied to demonstrate the drug loading and release capacity of the PMANs platform.Results: PMANs could simultaneously increase glutathione(GSH)consumption,suppress solute carrier family 7 member 11(SLC7A11)and glutathione-dependent peroxidases 4(GPX4)expression,and promote the generation of reactive oxygen species(ROS)and lipid peroxides(LPO).Besides,owing to its large surface area,PMANs efficiently transported doxorubicin(DOX)to prostate cancer for combinational therapy.Surprisingly,we found PMANs could sensitize prostate cancer cells to DOX through downregulating the expression of ataxia telangiectasia mutated(ATM),which further augmented GPX4 downregulation-mediated ferroptotic tumoricidal effect.Intriguingly,PMANs can suppress ATM expression,rendering the prostate cancer cells more sensitive to DOX.Conclusions: Given that arsenic trioxide has been routinely and successfully used in the clinical treatment of leukemia for a long time,we anticipate that PMANs should offer a promising strategy for prostate cancer therapy.