Iron oxide-EDTA nanoparticles for chelation-enhanced chemodynamic therapy and ion interference therapy.

As an emerging anti-tumor strategy, chemodynamic therapy (CDT) utilizes a Fenton/Fenton-like reaction to generate highly toxic hydroxyl radicals to kill tumor cells. However, the efficiency of CDT is still hindered by the low Fenton/Fenton-like reaction rate. Herein, we report the combination of ion interference therapy (IIT) and chemodynamic therapy (CDT) via an amorphous iron oxide (AIO) nanomedicine with encapsulated EDTA-2Na (EDTA). Iron ions and EDTA are released from the nanomedicine in acidic tumors and chelate to form iron ion-EDTA, which improves the efficiency of CDT and promotes the generation of reactive oxygen species (ROS). In addition, EDTA can disrupt the homeostasis of Ca2+ in tumor cells by chelating with Ca2+ ions, which induces the separation of tumor cells and affects normal physiological activities. Both in vitro and in vivo experiments show that the nano chelating drugs exhibit significant improvement in Fenton reaction performance and excellent anti-tumor activity. This study based on chelation provides a new idea for designing efficient catalysts to enhance the Fenton reaction and provides more revelations on future research on CDT.

Fe(III)-Naphthazarin Metal-Phenolic Networks for Glutathione-Depleting Enhanced Ferroptosis-Apoptosis Combined Cancer Therapy.

Nowadays, Fenton chemistry-based chemodynamic therapy (CDT) is an emerging approach to killing tumor cells by converting endogenous H2 O2 into cytotoxic hydroxyl radicals (·OH). However, the elimination of ·OH by intracellular overexpressed glutathione (GSH) results in unsatisfactory antitumor efficiency. In addition, the single mode of consuming GSH and undesirable drug loading efficiency cannot guarantee the efficient cancer cells killing effect. Herein, a simple one-step strategy for the construction of Fe3+ -naphthazarin metal-phenolic networks (FNP MPNs) with ultrahigh loading capacity, followed by the modification of NH2 -PEG-NH2 , is developed. The carrier-free FNP MPNs can be triggered by acid and GSH, and rapidly release naphthazarin and Fe3+ , which is further reduced to Fe2+ that exerts Fenton catalytic activity to produce abundant ·OH. Meanwhile, the Michael addition between naphthazarin and GSH can lead to GSH depletion and thus achieve tumor microenvironment (TME)-triggered enhanced CDT, followed by activating ferroptosis and apoptosis. In addition, the reduced Fe2+ as a T1 -weighted contrast agent endows the FNP MPNs with magnetic resonance imaging (MRI) functionality. Overall, this work is the debut of naphthazarin as ligands to fabricate functional MPNs for effectively depleting GSH, disrupting intracellular redox homeostasis, and enhancing CDT effects, which opens new perspectives on multifunctional MPNs for tumor synergistic therapy.

Facile Synthesis of a Cubic Porphyrin-Based Covalent Organic Framework for Combined Breast Cancer Therapy.

A cubic porphyrin-based covalent organic framework (COF) named CTP with excellent hydrophilicity was prepared with a facile method for the first time. Different from the conventional methods for the synthesis of porphyrin-based COFs, this facile strategy has greatly shortened the reaction time under mild conditions. Linking the porphyrin monomer into the COF overcame its poor solubility and biocompatibility and also narrowed the band gap owing to the formation of the π-conjugation structure. The improved biocompatibility and narrowed band gap enabled CTP to be an excellent sonosensitizer with an enhanced sonodynamic effect. Moreover, CTP could also effectively realize photothermal conversion under external irradiation due to the extended conjugated structure. This work developed a novel synthesis method for COFs and employed a COF as a sonosensitizer for the first time, which not only provided a new strategy to improve the efficiency of organic sonosensitizers but also inspired us to design more functional COFs for versatile applications.