The project is based on the hypothesis that SCNPs can break the osmotic balance across the plasma membrane of cancer cells. Ion homeostasis is essential for maintaining the integrity of the plasm membrane and sustaining the normal cell functions. Breaking the homeostasis could disrupt the potential balance and interrupt essential cellular processes. Instead of using organic ionophores, we explore SCNPs as a new strategy to carry ions across the plasma membrane, eventually causing cancer cell death.
Our extensive in vitro studies strongly support the hypothesis. Moreover, our results showed that SCNPs are more toxic to cancer cells than degraded NPs. We have 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. Last but not least, we observed that cancer cells succumbed to SCNPs released immunogenic cell death (ICD) signals including HMGB1, ATP, and CRT. Preliminary studies indicate that combination therapy with SCNPs and anti-PD-1 antibodies can trigger anti-cancer immune response, which contributes to inhibited tumor growth and metastasis.