Synergistic Amplification of Oxidative Stress–Mediated Antitumor Activity via Liposomal Dichloroacetic Acid and MOF‐Fe²⁺

Abstract

Cancer cells are susceptible to oxidative stress; therefore, selective elevation of intracellular reactive oxygen species (ROS) is considered as an effective antitumor treatment. Here, a liposomal formulation of dichloroacetic acid (DCA) and metal–organic framework (MOF)‐Fe2+ (MD@Lip) has been developed, which can efficiently stimulate ROS‐mediated cancer cell apoptosis in vitro and in vivo. MD@Lip can not only improve aqueous solubility of octahedral MOF‐Fe2+, but also generate an acidic microenvironment to activate a MOF‐Fe2+‐based Fenton reaction. Importantly, MD@Lip promotes DCA‐mediated mitochondrial aerobic oxidation to increase intracellular hydrogen peroxide (H2O2), which can be consequently converted to highly cytotoxic hydroxyl radicals (•OH) via MOF‐Fe2+, leading to amplification of cancer cell apoptosis. Particularly, MD@Lip can selectively accumulate in tumors, and efficiently inhibit tumor growth with minimal systemic adverse effects. Therefore, liposome‐based combination therapy of DCA and MOF‐Fe2+ provides a promising oxidative stress–associated antitumor strategy for the management of malignant tumors.

Reversing cold tumors to hot: An immunoadjuvant-functionalized metal-organic framework for multimodal imaging-guided synergistic photo-immunotherapy

“…In recent years, immunotherapy combined with nanotechnology, defined as nanoimmunotherapy, has shown promising performance for cancer therapy [ [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] ]. Among these therapeutics, metal-organic frameworks (MOFs), as a crystal material, has been widely studied in biomedical field [ [31] , [32] , [33] , [34] , [35] , [36] , [37] ]. MOFs of nanosized iron carboxylate, especially MIL101(Fe), have attracted considerable attention due to their excellent biocompatibility and biodegradability [ [38] , [39] , [40] ].…”

Tumor microenvironment-responsive fenton nanocatalysts for intensified anticancer treatment

“…The pH in the TME is 6.5–7, while the catalytic activity of MOF-Fe is extremely low in this physiological environment, which will limit the scope of its biological applications [ 37 ]. Some studies have shown that MOF-Fe catalysis of Fenton reaction can only be carried out in acidic media (pH is 2.0–5.0) [ 38 ]. To solve this problem, researchers designed pH-responsive MOFs that can regulate the TME.…”

Stimuli‐activatable nanomedicines for chemodynamic therapy of cancer

“…Lan et al, 2018). For instance, Sun et al reported a multifunctional nanoplatform by integrating dichloroacetic acid (DCA) into liposomal formulation and Fe-based MOF (MD@Lip), which can amplify the intratumoral ROS stress for management of the malignant tumors (L. Sun et al, 2019). The hybrid nanostructures could improve aqueous solubility of the octahedral MOFs, offering an acidic TME for Fenton reaction.…”

“…Fe‐based metal‐organic frameworks (MOFs) possess high porosity and tuneable surface functionalities, which are promising for improving the performance of Fenton reaction (W. Cai et al, ; G. Lan et al, ). For instance, Sun et al reported a multifunctional nanoplatform by integrating dichloroacetic acid (DCA) into liposomal formulation and Fe‐based MOF (MD@Lip), which can amplify the intratumoral ROS stress for management of the malignant tumors (L. Sun et al, ). The hybrid nanostructures could improve aqueous solubility of the octahedral MOFs, offering an acidic TME for Fenton reaction.…”