Promoting Dual-Targeting Anticancer Effect by Regulating the Dynamic Intracellular Self-Assembly.

Despite the promise of nanomedicine in the fight against complex diseases, the enthusiasm for its pharmaceutical development is backed by the elevated costs associated with the R&D process. Therefore, as a compromise solution, nanotechnology was mainly applied as a drug delivery system to improve bioavailability and controllability of pharmaceutical drugs. Attempting to break the restrictions without elevating potential costs, we multiply the functions of excipients in the nanodelivery system by endowing subcellular-targeting ability. To prove the concept, fluorescent endoplasmic reticulum-targeted short peptides were covalently connected to chemotherapy medication chlorambucil achieving enhanced drug-loading efficiency. Via visualized intracellular dynamic enzyme-catalyzed hydrolysis, the ER-targeting excipient and nucleus-targeting chlorambucil are released simultaneously, achieving a synergistic anticancer effect and elucidating the influence of intracellular self-assembly transition on enzymatic reactions.