Fig. 2

a Illustration of drug delivery of the PEG-CPT NRs. Once intravenously administrated, the PEG-CPT NRs were accumulated at the tumor site by the enhanced permeability and retention (EPR) effect-mediated passive tumor-targeting mechanism, were internalized by the tumor cells endocytosis, released CPT in a sustained manner, and intracellularly delivered CPT to the nucleus. b The MTX-PEG-CPT NRs with MTX self-targeting ligand enter tumor cells by FA receptor-mediated endocytosis and released both CPT and MTX anticancer drugs in tumor cells to be, respectively, delivered to nucleus and cytoplasm (CPT binds to DNA in the nucleus, and MTX binds to DHFR enzyme in the cytoplasm) for self-targeted multi-drug co-delivery and combination cancer therapy