Bioconjug Chem. 2025 Mar 5. doi: 10.1021/acs.bioconjchem.4c00546. Online ahead of print.
ABSTRACT
Exogenous iron delivery using iron-containing nanomaterials is an alternative strategy for enhancing the efficacy in ferroptosis tumor therapy but limited by the problems of low iron content, low tumor enrichment, low cellular uptake, and uncontrolled release of iron ions. To solve the problems, an FeOOH-assisted approach is demonstrated to produce iron hybrid polymer nanospindles (IHPNSs) for efficient iron delivery and ferroptosis tumor therapy. The IHPNSs are prepared through the cohydrolysis of FeCl3·6H2O with aniline, pyrrole, or amino-pyrrole. On the one hand, the hydrolysis of Fe3+ generates FeOOH particles, which further act as the templates to form fusiform architectures. On the other hand, Fe3+ triggers the oxidative polymerization of aniline, pyrrole, or amino-pyrrole. The as-prepared polymers are capable of coordinating with excessive Fe3+ and locate on the FeOOH templates, thus producing Fe3+/polymer composite-coated FeOOH nanospindles. Systematic studies indicate that the one-dimension-like morphology facilitates tumor enrichment and cellular uptake of IHPNSs. Besides the high iron content of IHPNSs, the controlled release of Fe3+ stimulated by the overexpressed glutathione (GSH) in the tumor microenvironment is achieved. The released Fe3+ is further transformed to Fe2+ by scavenging GSH, which leads to excessive accumulation of reactive oxygen species and lipid peroxides and finally induces ferroptosis of tumor cells. As a proof of concept, the IHPNSs show good efficacy in the treatment of a rat model of bladder tumors in situ.
PMID:40045454 | DOI:10.1021/acs.bioconjchem.4c00546
