Cesium Nanosalts: Trojan Horse Strategy for Anti-Cancer Treatment
Biodegradable Cesium Nanosalts Activate Anti-Tumor Immunity
A team led by Academician Hongjie Zhang,Researcher Shuyan Song,Associate Researcher Pengpeng lei,and Dr. Ran An at the Changchun Institute of Applied Chemistry, chinese Academy of Sciences, has developed an innovative strategy to construct a series of biodegradable cesium nanosalts.These nanosalts activate anti-tumor immunity by inducing pyroptosis and metabolic intervention.
The nanosalts induce ion endocytosis in tumor cells using a Trojan horse strategy,disrupting intracellular ion homeostasis,causing a surge in osmotic pressure,and ultimately triggering pyroptosis. Cesium ions (Cs+) inhibit the ion channel activity of sodium/glucose cotransporters, hindering glucose transport. The introduction of docosahexaenoic acid (DHA) amplifies pyroptosis and initiates immunogenic ferroptosis. These multiple effects lead to the release of damage-related molecular patterns (DAMPs), activating a robust anti-tumor immune response.The research was published in CCS Chemistry, the flagship journal of the Chinese Chemical Society.
background
Nanosalts are a promising class of tumor therapeutic agents. They bypass ion pumps/channels and enter cells via plasma membrane endocytosis. Their high water solubility allows them to dissolve and release ions, disrupting ion homeostasis. The resulting reverse osmotic gradient increases osmotic pressure, leading to cell lysis via pyroptosis. this releases DAMPs and pro-inflammatory cytokines, reprogramming the immunosuppressive tumor microenvironment and triggering a strong inflammatory response.DAMPs promote antigen presentation, immune cell infiltration, and activation of anti-tumor immune responses.
Currently, the library of nanosalts is limited, and many soluble electrolytes haven’t been nanoscaled. Developing new preparation strategies and expanding this library, especially with nanosalts possessing ion-interference therapeutic functions, is crucial for addressing challenges in malignant tumor treatment.
Highlights of this Research
This study achieved the directed synthesis of cesium-based nanosalts, using cesium bromide nanosalts as a proof-of-concept for pyroptosis-based tumor immunotherapy. Key highlights include:
- Development of a novel method for synthesizing cesium-based nanosalts, allowing for wide-range control of nanosalt size.
- The nanosalts utilize a “Trojan horse” strategy for ion endocytosis.