Peptosome Coadministration Improves Nanoparticle Delivery to Tumors through NRP1-Mediated Co-Endocytosis

Improving the efficacy of nanoparticles (NPs) delivery to tumors is critical for cancer diagnosis and therapy. In our previous work, amphiphilic peptide APPA self-assembled nanocarriers were designed and constructed for cargo delivery to tumors with high efficiency. In this study, we explore the use of APPA self-assembled peptosomes as a nanoparticle adjuvant to enhance the delivery of nanoparticles and antibodies to integrin αvβ3 and neuropilin-1 (NRP1) positive tumors. The enhanced tumor delivery of coadministered NPs was confirmed by better magnetosome (Mag)-based T₂-weighted magnetic resonance imaging (MRI), liposome-based fluorescence imaging, as well as the improved anti-tumor efficacy of monoclonal antibodies (trastuzumab in this case) and doxorubicin (DOX)-containing liposomes. Interestingly, the improvement is most significant for the delivering of compounds that have active or passive tumor targeting ability, such as antibodies or NPs that have enhanced permeability and retention (EPR) effect. However, for non-targeting small molecules, the effect is not significant. In vitro and in vivo studies suggest that both peptosomes and the coadministered compounds might be internalized into cells through a NRP1 mediated co-endocytosis (CoE) pathway. The improved delivery of coadministered NPs and antibodies to tumors suggests that the coadministration with APPA self-assembled peptosomes could be a valuable approach for advancing αvβ3 and NRP1 positive tumors diagnosis and therapy.