Phosphate imbalance conducting by BPs-based cancer-targeting phosphate anions carrier induces necrosis

As a vital nutrient closely related to the cance r-cells proliferation,phosphate anions have been paid great attention as a promising anticancer agent.Generally,the transport of phosphate anions depends on a protein transport system which is regulated by ion homeostasis regulations.Herein,we designed a reactive anionic nanocarrier based on black phosphorus nanosheets(BPs)and artesunate(ART),which could enter cells through endocytosis to generate phosphate anions,avoiding the regulation of cell homeostasis.The ionic nanocarrier was coated by polydopamine to defend BPs and ART and functionalized by folate(FA)and hyaluronic acid(HA)for targeting factor.With the anchoring groups FA/HA targeted the carrier into cells,polydopamine coating decomposed to expose ART for further generating reactive oxygen species(ROS)in cancer cell microenvironment,providing oxidation conditions.Next,ROS generated by ART makes BPs decompose to phosphate anions with effectively speed,giving rise to the destruction of ion homeostasis to induce necro sis and inhibit the proliferation for cancer cells.In consequence,this research provides novel idea and direction for the ionic carriers and tumor therapeutics.

A nanocarrier based on poly(D,L-lactic-co-glycolic acid) for transporting Na^+ and Cl^- to induce apoptosis

Transmembrane anion transporters have attracted significant attention as therapeutic agents because of their potential to disrupt cellular ion homeostasis,in which,most of the synthetic anionic transporters are organic small molecules whose synthesis routes are usually complex and tedious,and the related biological research is also only in infancy.Hence,we synthesized a kind of chloride anion(Cl-)and sodium cation(Na^+)nanocarrier based on poly(D,L-lactic-co-glycolic acid)(PLGA)which was coated with polydopamine(PDA)to provide target release factor.When the nanocarrier arrives in acidic enviro nment such as lysosomes through endocytosis,Cl^-and Na^+will be released fast from the nanocarrier resulting in imbalance of cell homeostasis for inducing apoptosis.Cell experiments show that the nanocarrier promotes apoptosis and leads to an increased concentration of reactive oxygen species.By exploring the concentration of cytochrome c in mitochondria and cytoplasm and the activities of key enzymes caspase-9 and caspase-3 in apoptosis process,it is proved that the apoptotic pathway is caspase-dependent.This novel strategy allows the research of anion transporter no longer limited to artificial synthesis of small molecular and provides a novel and effective direction to investigate ion homeostasis,ion transport and cancer treatment.