Files
Abstract
Alkali halide nanoparticles, derived from elements in Group IA and Group VIIA of the Periodic Table, have garnered interest for their potential applications in various biomedical fields. Particularly, sodium chloride nanoparticles (SCNPs) challenge the conventional belief that salt nanoparticles exhibit identical behavior to their constituent salts. The main project is based on the hypothesis that SCNPs can disrupt the osmotic balance across the plasma membrane of cancer cells. Ion homeostasis is essential for maintaining the integrity of the plasma membrane and sustaining normal cell functions. Disruption of homeostasis could disrupt the potential balance and interrupt essential cellular processes. Instead of using organic ionophores, we are exploring SCNPs as a new strategy to transport ions across the plasma membrane and ultimately cause cancer cell death. While the plasma membrane is not permeable to ions, we hypothesize that SCNPs can enter the cell by endocytosis and degrade inside the cell, releasing large quantities of ions into cancer cells therein. Our extensive in vitro studies strongly support this hypothesis. Moreover, our results showed that SCNPs are more toxic to cancer cells than to normal cells. This is because cancer cells have higher intracellular sodium levels, making them more susceptible to SCNPs-induced ion disruption. We tested SCNPs in vivo in tumor models established with MB49 and other bladder cancer cell lines. Our data confirmed that SCNPs can effectively suppress tumor growth without causing additional systemic toxicity. In addition, we observed that cancer cells exposed to SCNPs released immunogenic cell death (ICD) signals, including HMGB1, ATP, and CRT. Preliminary studies suggest that combination therapy with SCNPs and anti-PD-1 antibodies can induce an anti-cancer immune response that contributes to inhibited tumor growth and metastasis. We have also observed evidence supporting the potential use of SCNPs as radiosensitizers. Taken together, SCNPs represent a novel and promising cancer therapeutic strategy.