This study aims to prepare a novel breast cancer-targeted micelle-based nanocarrier, which is stable in circulation, allowing intracellular drug release, and to investigate its cytotoxicity, apoptosis, and cytostatic effects, in vitro. The shell part of the micelle is composed of zwitterionic sulfobetaine ((N-3-sulfopropyl-N,N-dimethylamonium)ethyl methacrylate), while the core part is formed by another block, consisting of AEMA (2-aminoethyl methacrylamide), DEGMA (di(ethylene glycol) methyl ether methacrylate), and a vinyl-functionalized, acid-sensitive cross-linker. Following this, a targeting agent (peptide (LTVSPWY) and antibody (Herceptin®)), in varying amounts, were coupled to the micelles, and they were characterized by 1H NMR, FTIR (Fourier-transform infrared spectroscopy), Zetasizer, BCA protein assay, and fluorescence spectrophotometer. The cytotoxic, cytostatic, apoptotic, and genotoxic effects of doxorubicin-loaded micelles were investigated on SKBR-3 (human epidermal growth factor receptor 2 (HER2)-positive) and MCF10-A (HER2-negative). According to the results, peptide-carrying micelles showed a higher targeting efficiency and better cytostatic, apoptotic, and genotoxic activities than antibody-carrying and non-targeted micelles. Also, micelles masked the toxicity of naked DOX on healthy cells. In conclusion, this nanocarrier system has great potential to be used in different drug-targeting strategies, by changing targeting agents and drugs.

Background: Metastatic castration-resistant prostate cancer (mCRPC) is the most challenging stage in prostate cancer. Patient with visceral metastasis have the poorest outcome amoung them. In this retrospective study, we analyzed the clinical outcome of lutetium-177 prostate-specific membrane antigen (177 Lu-PSMA) in mCRPC patients with visceral metastasis. Methods: Ten patients of mCRPC with visceral metastasis were enrolled for one cycle of 177 Lu-PSMA therapy. Number of efficacy and safety parameters, e.g., prostatespecific antigen (PSA), visual analog scale (VAS) and analgesic quantification scale (AQS), hemoglobin (Hb), total leukocytes counts (TLC), platelets, creatinine, & total bilirubin, were assessed and compared with Wilcoxon signed-rank test. The progression-free survival (PFS) curve was computed by the Kaplan-Meier method. The receiver operating characteristic curve (ROC) was also plotted for 177 Lu-PSMA dose. P 0.05 was considered significant. Results: Liver (80%), lung (30%), adrenal (10%), and peritoneum (10%) were the sites of visceral metastasis in our study. On PSA response assessment, 10%, 60%, and 30% of the patients had partial response, stable disease, and progressive disease, respectively. Forty percent of the patients had improvement in the VAS, while 50% had improvement in the AQS score. Median PFS was 24 weeks in our study. A cutoff of 4.88GBq of 177 Lu-PSMA was the best-predicted progression with 66.67% sensitivity and 100% specificity on ROC analysis. Thirty percent of the patients showed grade 3 anemia. No other significant toxicity was seen. Conclusions: Lutetium-177-PSMA was a reasonable palliative treatment option with limited toxicity for these end-stage mCRPC patients with visceral metastasis with adequate PSA stabilization. Legal entity responsible for the study: The authors.