Magnetically-actuated drug delivery device (MADDD) for minimally invasive treatment of prostate cancer: An in vivo animal pilot study

Background: The vast majority of prostate cancer presents clinically localized to the prostate without evidence of metastasis. Currently, there are several modalities available to treat this particular disease. Despite radical prostatectomy demonstrat- ing a modest prostate cancer specific mortality benefit in the PIVOT trial, several novel modalities have emerged to treat localized prostate cancer in patients that are either not eligible for surgery or that prefer an alternative approach. Methods: Athymic nude mice were subcutaneously inoculated with prostate cancer cells. The mice were divided into four cohorts, one cohort untreated, two cohorts receiveddocetaxel (10mg/kg) either subcutaneously(SC)or intravenously(IV)andthe fourth cohort was treated using themagnetically-actuated docetaxel delivery device (MADDD), dispensing 1.5μg of docetaxel per 30 min treatment session. Treatment in all three therapeutic arms (SC, IV, and MADDD) was administered once weekly for 6 weeks. Treatment efficacy was measured once a week according to tumor volume using using ultrasound. In addition, calipers were used to assess tumor volume. Results: Animals implanted with the device demonstrated no signs of distress or discomfort, neither local nor systemicsymptomsof inflammationandinfection. Using an independent sample t-test, the tumor growth rate of the treated tumors was significant when compared to the control. Post hoc Tukey HSD test results showed that themeantumor growth rate of our device cohortwassignificantly lower thanSC and control cohorts. Moreover, IV cohort showed slight reduction in mean tumor growth rates than the ones from the device cohort, however, there was no statistical significance in tumor growth rate between these two cohorts. Furthermore, immunohistochemistry demonstrated an increased cellular apoptosis in theMADDD treated tumors and a decreased proliferationwhencompared to the other cohorts. In addition, IV cohort showed increased treatment side effects (weight loss) when compared to the device cohort. Finally, MADDD showed minimal expression of CD45comparable to the control cohort, suggesting no signs of chronic inflammation. Conclusions: In conclusion, this study showed for the first time thatMADDD,clearly suppressed tumor growth in local prostate cancer tumors. This could potentially be a novel clinical treatment approach for localized prostate cancer.