Evaluation of Single Dose and Fractionated Dose of I-131 Radiolabeled Nanoparticles for Triple-Negative Breast Cancer Treatment.

Abstract

Combination chemotherapy is still the standard clinical care for triple-negative breast cancer (TNBC). However, sodium iodide symporter (NIS) uptake by TNBC has opened the potential of NIS as a molecular target for radioiodine theranostic treatments. Radiolabeled poly(lactic-co-glycolic) acid nanocarrier (NINP) was developed for NIS targeted delivery of I-131 to MDA-MB-231 cells to overcome I-131 low uptake in cancer cells and rapid clearance. The NINP diameter of 237 nm has good particle size uniformity and excellent particle stability. Radiochemical purity, radioactive stability, and radiolabeling yield of NINPs over 72 h were >95%. Cytotoxicity confirmed fractionated NINPs over 72 h to be more effective in cell death than single-dose NINP and both single and fractionated Na131I. Cellular uptake in a three-dimensional spheroid confirmed that NINP fractionated-dose achieved ~4.8-fold-higher mean fluorescent intensity than Na131I and ~2.7-fold greater reduction in cell viability compared to single-dose. The NINP fractionated-dose initiated greater cellular DNA damage to cells than single-dose NINP, resulting in inhibition of cell cycle progression, resulting in cell cycle progression being inhibited by cyclin-dependent kinases, which play a vital role in the control of MDA-MB-231 cell cycle. NINPs are biocompatible with blood, and were found to have no negative impact on red blood cells.