Mitochondrial targeted prodrug nanoparticles for chemo-photodynamic combinational tumour therapy

Prodrug nanoparticles have been explored as an effective means for drug delivery because of controlled drug release in a stimulus-responsive manner. Organellar-targeted drug delivery could enhance the efficacy of cancer therapy. Herein, pH and light dual responsive mitochondrial targeted prodrug nanoparticles were designed to deliver both chemotherapeutic drugs and photosensitisers for enhanced antitumour efficacy. The prodrug nanoparticles (TPP-PEI-PheoA/ALG=DOX NPs, TPPAD NPs) are composed of a light-responsive mitochondrial targeted prodrug (triphenylphosphonium and pheophorbide A modified polyethyleneimine, TPP-PEI-PheoA) and a pH-responsive prodrug (doxorubicin conjugated alginate with Schiff's base bond, ALG=DOX). TPPAD NPs were prepared through electrostatic interaction. TPPAD NPs could simultaneously deliver DOX and PheoA to the tumour site by passive targeting effect, release drugs in a designed mode and deliver drugs to the target organelles. Moreover, TPPAD NP-based PDT could induce immunogenic cell death of tumour cells, thereby activating the immune system. TPPAD NPs greatly enhanced antitumour efficacy by combinational therapy. Taken together, this prodrug nanoparticle platform has appeared to be a simple and smart nanomedicine for targeted tumour combinational treatment. © 2024 The Authors