Updated project metadata. Temperature and pH-sensitive, self-assembled polymeric nanoparticles, made of N-isopropyl acrylamide (NIPAAM), N-vinyl pyrrolidone (VP), and acrylic acid (AA) are biocompatible and have been used in the past with several drugs for site-specific delivery of different formulations. In the present study, the nano LC-MS/MS proteomic approach was employed to compare the secretome of Artemisia absinthium extract loaded polymeric nanoparticles-treated MCF-7 and MDA MB-231 cell lines targeted against the tumor microenvironment and comparison with corresponding untreated cell lines as a control to identify potential therapeutic targets and easily-accessible biomarkers among differentially expressed secretory proteins.