Multifunctional nanoplatforms as cascade-responsive drug-delivery carriers for effective synergistic chemo-photodynamic cancer treatment

Abstract Synergistic chemo-photodynamic therapy has garnered attention in the field of cancer treatment. Here, a pH cascade-responsive micellar nanoplatform with nucleus-targeted ability, for effective synergistic treatment, was fabricated. In this nanoplatform, 5-(4-carboxyphenyl)-10,15,20-triphenylporphyrin (Por), photodynamic (PDT) agent utilized carrying novel anticancer drug GNA002 to construct hydrophobic core, and cyclic RGD peptide (cRGD)-modified polyethylene glycol (PEG) (cRGD-PEG) connected cell-penetrating hexaarginine (R 6 ) through pH-responsive hydrazone bond (cRGD-PEG-N = CH-R serve as hydrophilic shell increasing blood circulation time. After passively accumulating tumor sites, self-assembled GNA002-loaded nanoparticles were actively internalized into cells via cRGD ligands. Once phagocytosed by lysosomes, acidity-triggered detachment cRGD-PEG led formation R -coated secondary subsequent -mediated delivery. Combined GNA002-induced nucleus-specific chemotherapy, reactive oxygen species produced Por under 532-nm laser irradiation achieved potent Moreover, our vitro vivo investigations revealed high cancer-suppression efficacy ideal multifunctional indicating that it could be promising candidate therapy.