Amorphous Fe‐Based Nanoagents for Self‐Enhanced Chemodynamic Therapy by Re‐Establishing Tumor Acidosis

Abstract

Chemodynamic therapy (CDT) by introducing the Fenton-/Fenton-like reaction in an acidic and H 2 O 2 environment for toxic hydroxyl radical (•OH) generation, is a newly developed tumor-selective therapeutic. However, tumor acidosis, characterized by extracellular acidity (pH e ≈ 6.5) and intracellular alkalinity (pH i ≈ 7.2), undoubtedly confers a large chemical barrier for effective implementation of intracellular CDT and thus limits its functional activity and therapeutic efficacy. Here, the unique amorphous iron nanoparticles (AFeNPs) loaded with carbonic anhydrase IX inhibitor (CAI) are constructed to re-establish tumor acidosis with decreased pH i and increased pH e via inhibiting the over-expressed CA IX in cancer cells by CAI for self-enhanced CDT. The suppression of CA IX leads to H + accumulation in cells that could accelerate the AFeNPs-based Fenton reaction to drastically exacerbate oxidative stress in cells and subsequently induce cell death; meanwhile, the inhibition of H + formation outside cells efficiently represses the potential of tumor invasion and metastasis owing to the insufficient acidic ions for degradation of tumor extracellular matrix. Re-establishedtumor acidosis not only assists in the optimization of CDT, but also presents an opportunity for the development of new antitumor methods that are more tumor-acidity specific.

An Ultrasmall SnFe2O4 Nanozyme with Endogenous Oxygen Generation and Glutathione Depletion for Synergistic Cancer Therapy

“…Lately, catalytic reactions based on multivalent metal ions (such as Fe 2+ /Fe 3+ , Cu + /Cu 2+ , and Mn 2+ /Mn 4+ ) in nanozymes, which imitate the functions of natural enzymes, have displayed a conspicuous effect in accommodating TME and then improving the treatment outcome. [45][46][47][48] For instance, Zhang et al synthesized MnFe 2 O 4 @MOF (MOF = metal-organic framework) nanostructure with both catalase-like and GSH peroxidase-like activities, consecutively generating O 2 and depleting overexpressed GSH to modulate TME for achieving high antitumor effect. [49] Lin and co-workers prepared hollow mesoporous Cu 2 MoS 4 loaded glucose oxidase, which could effectively relieve tumor hypoxia and antioxidant capacity of tumor, showing improved antitumor efficacy combined with the photo therapy upon 808 nm laser irradiation.…”

Mechanisms of Reactive Oxygen Species Generated by Inorganic Nanomaterials for Cancer Therapeutics

“…Bu et al developed AFeNPs@CAI nanocomposites from amorphous iron nanoparticles (AFeNPs) loaded with carbonic anhydrase IX inhibitor (CAI). The release of CAI led to the accumulation of H + , which accelerated the Fenton reaction and amplified the oxidative damage of cells ( Chen et al, 2019 ). Fenton-like reactions catalyzed by Cu + are kinetically more favorable than those catalyzed by Fe 2+ under neutral and weakly acidic conditions.…”

Energy‐converting biomaterials for cancer therapy: Category, efficiency, and biosafety

“…Unfortunately, these aforementioned organic agents suffer from some specific drawbacks such as low bioavailability and stability, short blood circulation time, and reluctant tumor‐accumulation, severely restricting the efficiency of SDT (Chen et al, 2017; Paris & Vallet‐Regí, 2020; Yue et al, 2019). To overcome these obstacles, MSNs are desirable organic sonosensitizers reservoirs due to the large surface area and tunable pore size, high biocompatibility, and rapid biodegradation (Chen et al, 2019; Knezevic & Kaluderovic, 2017; Zhou et al, 2020). Li, Kwon, et al (2018) constructed a targeted biodegradable mesoporous sonosensitizer‐relevant nanosystem (DOX@HMONs‐PpIX‐RGD) for synergistic SDT/chemotherapy (Figure 3a).…”