Trojan Horse Strategy Using Cesium Nanosalts Shows Powerful Anti-cancer Effects

Recently, a squad led by Academician Hongjie Zhang, Researcher Shuyan Song, Associate Researcher Pengpeng Lei, and Dr. Ran An astatine nan Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, developed an innovative strategy to conception a bid of biodegradable cesium nanosalts. These nanosalts activate anti-tumor immunity by inducing pyroptosis and metabolic intervention. The nanosalts induce ion endocytosis successful tumor cells utilizing a Trojan equine strategy, disrupting intracellular ion homeostasis, causing a surge successful osmotic pressure, and yet triggering pyroptosis. Cesium ions (Cs+) tin inhibit nan ion transmission activity of sodium/glucose cotransporters, hindering glucose transport. The preamble of docosahexaenoic acerb (DHA) not only amplifies pyroptosis but besides initiates immunogenic ferroptosis. The aggregate effects of nan nanosalts lead to nan merchandise of damage-related molecular patterns, thereby activating a robust anti-tumor immune response. The article was published arsenic an unfastened entree investigation article in CCS Chemistry, nan flagship diary of nan Chinese Chemical Society.

Background information:

Nanosalts, arsenic an important branch of fantabulous tumor therapeutic agents, merit afloat nickname for their value. Nanosalts tin bypass ion pumps/channels and participate cells via plasma membrane endocytosis. Due to their precocious h2o solubility, nanosalts gradually dissolve and merchandise ions. When these ions accumulate to a definite concentration, they disrupt ion homeostasis. Simultaneously, owed to nan reverse osmotic gradient formed crossed nan plasma membrane, these ions are trapped wrong nan cell, starring to a crisp summation successful osmotic pressure. The resulting compartment lysis is not only a beingness process but besides involves nan pyroptosis-mediated pathway. Cell swelling and cytoplasmic efflux merchandise ample amounts of damage-associated molecular patterns (DAMPs) and pro-inflammatory cytokines, yet triggering a beardown inflammatory consequence that reprograms nan immunosuppressive tumor microenvironment, causing its regression. Once recognized by phagocytosis-related receptors, DAMPs tin beforehand antigen presentation, induce wide immune compartment infiltration, and activate anti-tumor immune responses.

However, compared pinch different nanomaterials, nan room of nanosalts is still not rich | enough, and galore soluble electrolytes person not yet been nanoscaled. Developing caller mentation strategies and expanding nan room of nanosalts, particularly nanosalts pinch ion-interference therapeutic functions, is peculiarly important for addressing nan challenges of treating malignant tumors.

Highlights of this article:

In this study, nan authors achieved nan directed synthesis of cesium-based nanosalts and utilized cesium bromide nanosalts arsenic a proof-of-concept to behaviour investigation connected pyroptosis-based tumor immunotherapy. The main highlights of this activity include: 1) nan improvement of a caller method for synthesizing cesium-based nanosalts, allowing for wide-range power of nanosalt size; 2) nan nanosalts utilize a "Trojan horse" strategy to flooded ion transmission barriers, delivering ions into nan compartment via endocytosis, inducing a surge successful osmotic unit and triggering pyroptosis, releasing DAMPs, and activating a systemic anti-tumor immune response; 3) Cs+ can interfere pinch nan plasma membrane potential, inhibiting glucose uptake by affecting nan usability of sodium/glucose cotransporters, thereby disrupting tumor metabolic homeostasis; 4) nan dietary nutrient DHA not only enhances nan pyroptosis effect but besides induces immunogenic ferroptosis, forming a dual synergistic therapeutic mechanism; and 5) nan anti-tumor immune consequence of nan nanosalts was systematically verified done successful vitro and successful vivo experiments, demonstrating their important expertise to inhibit tumor penetration and metastasis.

Summary and outlook:

In summary, this activity successfully constructed a biodegradable cesium-based nanosalt system, processing a singular anti-tumor immunotherapeutic agent. Through liposome encapsulation technology, nan pyroptosis inducer DHA was successfully loaded while simultaneously regulating nan ion dissolution and merchandise rate, forming a complete therapeutic system. This nanosalt overcomes ion transmission limitations, employing a "Trojan horse" strategy to induce ion endocytosis successful tumor cells, disrupting intracellular ion homeostasis, triggering an osmotic unit surge, and starring to pyroptosis. DHA not only enhances nan pyroptosis effect but besides induces a synergistic effect of ferroptosis. Intracellularly released cesium ions interfere pinch nan usability of sodium-glucose cotransporters, inhibiting glucose uptake and frankincense disrupting metabolic balance. Under nan synergistic effect of aggregate pathways, a ample magnitude of DAMPs are released, successfully activating nan successful vivo anti-tumor immune response. On nan 1 hand, it promotes nan maturation of lymph node dendritic cells, mediating downstream immune responses by regulating T compartment proliferation; connected nan different hand, it drives a ample infiltration of immune cells, efficaciously inhibiting tumor proliferation and metastasis. This study confirms that nanosalts are highly promising anti-tumor agents, and nan improvement of next-generation nanosalts provides a reliable pathway for businesslike tumor treatment.

These results were published arsenic a investigation article in CCS Chemistry. Academician Hongjie Zhang, Researcher Shuyan Song, Associate Researcher Pengpeng Lei, and Dr. Ran An from Changchun Institute of AppliedChemistry, Chinese Academy of Sciences are nan corresponding authors, and Pengye Du is nan first author.