Ultrastable and Biofunctionalizable Conjugated Polymer\nNanoparticles with Encapsulated Iron for Ferroptosis Assisted Chemodynamic\nTherapy

Abstract

We report the development of novel\ntumor-targeted conjugated polymer\nnanoparticles (CPNPs) carrying iron for chemodynamic therapy (CDT).\nTumor cell killing proceeds through ferroptosis, a reactive oxygen\nspecies (ROS) mechanism that is not dependent on external activation\nby, for example, light, as is the case in photodynamic therapy (PDT).\nThe ferroptosis mechanism is also not heavily reliant on oxygen availability\nand is, therefore, promising for the treatment of hypoxic tumors.\nIn this work, we apply this development to the case study of melanoma,\na difficult to treat cancer in advanced stages due to resistance to\nchemotherapy. The iron-carrying CPNPs reported here are targeted to\nendothelin-B receptors (EDNRB) through endothelin-3 surface moieties\n(EDN3-CPNPs). Our results show excellent targeting to tumor cells\nthat overexpress EDNRB, specifically for melanoma and bladder tumor\ncells. In these cases, efficient cell killing, over 80% at higher\ndoses, was found. Conversely, tumor cells not targeted by the EDN3-CPNPs\nshow little effects of CDT, with tumor cell death under 20% in most\ncases. The outcomes of our work demonstrate that EDN3-CPNPs enable\nferroptosis-assisted CDT and present a new therapeutic avenue for\ntumor treatment.