Biomimetic Nanoparticles with Sustained-Release for Stepwise Targeting Ion Channels in Inhibiting Leukemia Cell Growth.

Acute myeloid leukemia (AML) is extremely difficult to cure due to the challenges in accurately targeting it, as it is characterized by rapid progression, high aggressiveness, and high drug resistance. In this study, biomimetic sustained release nanoparticles (PLGA-C-M) were designed and prepared to inhibit the survival and resistance pathways of AML. PLGA-C-M targeted AML cells by wrapping leukemia cell membranes, achieving sustained slow drug release in the blood, and then progressively affecting intracellular Ca2+ signaling by targeting TRPM2 ion channels that were highly expressed in AML in a step-by-step manner. PLGA-C-M can inhibit the growth of AML cells from three aspects: destroying mitochondrial function, reducing autophagy, and overcoming the drug resistance of cancer cells. Biomimetic nanoparticles achieved simultaneous regulation of intracellular ROS and Ca2+ signals to inhibit the growth of leukemia cells and provided ideas for the regulation of ion channel-related signal transduction in AML.