Fig. 1.

A schematic illustration of the synthesis of RGD-f-PNPs/EPI and its targeted EPI delivery into EC cells. a The RGD-f-PNPs were first synthesized by co-assembly Zn²⁺ ions and cyclo[-(d-Ala-L-Glu-D-Ala-L-Trp)₂-] peptides, and then modified with RGD peptide moieties onto the surface of f-PNPs. The EPI was loaded with RGD-f-PNPs through π–π stacking and electrostatic interactions. b The EPI-loaded RGD-f-PNPs can be used for targeted imaging and destruction of EC cells due to their capability of actively targeting and enhanced penetration. Specifically, the RGD-f-PNPs/EPI nanoconjugates tend to accumulate in the tumor tissue compared to normal tissues due to the enhanced permission and retention (EPR effects). Moreover, RGD peptide moieties bind to the overexpressed α_vβ₃ integrin subunits and internalize into EC cells. The embedded EPI will be released from the RGD-f-PNPs and eventually accumulates in the nucleus to kill the cancer cells