We report the development of novel
tumor-targeted conjugated polymer
nanoparticles (CPNPs) carrying iron for chemodynamic therapy (CDT).
Tumor cell killing proceeds through ferroptosis, a reactive oxygen
species (ROS) mechanism that is not dependent on external activation
by, for example, light, as is the case in photodynamic therapy (PDT).
The ferroptosis mechanism is also not heavily reliant on oxygen availability
and is, therefore, promising for the treatment of hypoxic tumors.
In this work, we apply this development to the case study of melanoma,
a difficult to treat cancer in advanced stages due to resistance to
chemotherapy. The iron-carrying CPNPs reported here are targeted to
endothelin-B receptors (EDNRB) through endothelin-3 surface moieties
(EDN3-CPNPs). Our results show excellent targeting to tumor cells
that overexpress EDNRB, specifically for melanoma and bladder tumor
cells. In these cases, efficient cell killing, over 80% at higher
doses, was found. Conversely, tumor cells not targeted by the EDN3-CPNPs
show little effects of CDT, with tumor cell death under 20% in most
cases. The outcomes of our work demonstrate that EDN3-CPNPs enable
ferroptosis-assisted CDT and present a new therapeutic avenue for
tumor treatment.
Most nanomedicines that attack tumors by Reactive Oxygen Species (ROS) based on lipid peroxidation mechanisms require external activation to work. The leading example is Photodynamic Therapy (PDT), for which an...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.