CoFeSe2 @DMSA@FA Nanocatalyst for Amplification of Oxidative Stress to Achieve Multimodal Tumor Therapy.

Nanomedicine has significantly advanced precise tumor therapy, providing essential technical blessing for active drug accumulation, targeted consignment, and mitigation of noxious side effects. To enhance anti-tumor efficacy, the integration of multiple therapeutic modalities has garnered significant attention. Here, we designed an innovative CoFeSe2 @DMSA@FA nanocatalyst with Se vacancies (abbreviated as CFSDF), which exhibits synergistic chemodynamic therapy (CDT) and photothermal therapy (PTT), leading to amplified tumor oxidative stress and enhanced photothermal effects. The multifunctional CFSDF nanocatalyst exhibits the remarkable ability to catalyze the Fenton reaction within the acidic tumor microenvironment, efficiently converting hydrogen peroxide (H2 O2 ) into highly harmful hydroxyl radicals (⋅OH). Moreover, the nanocatalyst effectively diminishes GSH levels and ameliorates intracellular oxidative stress. The incorporation of FA modification enables CFSDF to evade immune detection and selectively target tumor tissues. Numerous in vitro and in vivo investigations have consistently demonstrated that CFSDF optimizes its individual advantages and significantly enhances therapeutic efficiency through synergistic effects of multiple therapeutic modalities, offering a valuable and effective approach to cancer treatment.

Precisely designed Fex (x = 1-2) cluster nanocatalysts for effective nanocatalytic tumor therapy.

Atomically dispersed metal clusters are considered as promising nanocatalysts due to their excellent physicochemical properties. Here, we report a novel strategy for precisely designing Fex (x = 1-2) cluster nanocatalysts (Fe1-N-C and Fe2-N-C) with dual catalytic activity, which can catalyze H2O2 into reactive oxygen species (ROS) and oxidize glutathione (GSH) into glutathione disulfide simultaneously. The adsorption energies of Fe-N sites in Fe2-N-C for GSH and H2O2 intermediates were well controlled due to the orbital modulation of adjacent Fe sites, contributing to the higher dual catalytic activity compared to Fe1-N-C. Additionally, tamoxifen (TAM) was loaded into Fe2-N-C (Fe2@TDF NEs) to down-regulate the intracellular pH for higher Fenton-like catalytic efficiency and ROS production. The generated ROS could induce apoptosis and lipid peroxidation, triggering ferroptosis. Meanwhile, upregulation of ROS and lipid peroxidation, along with GSH depletion and GPX4 downregulation could promote the apoptosis and ferroptosis of tumor cells. In addition, the lactic acid accumulation effect of TAM and the high photothermal conversion ability of Fe2@TDF NEs could further enhance the catalytic activity to achieve synergistic antitumor effects. As a result, this work highlights the critical role of adjacent metal sites at the atomic-level and provides a rational guidance for the design and application of nanocatalytic antitumor systems.

Precision therapy through breaking the intracellular redox balance with an MOF-based hydrogel intelligent nanobot for enhancing ferroptosis and activating immunotherapy.

With the advancement and development of nanomedicine, tumor precision therapy provides technical support for effective accumulation and targeted drug delivery, and reduces toxic side effects. In cancer cells, breaking the redox balance could induce cancer cell death. Herein, a novel iron-containing intelligent hydrogel nanobot (FeSe2-Ce6/MOF@HA/PEI/CpG@HHPA NPs, abbreviated as FSMH) is proposed to break the intracellular redox balance and trigger the immune response. The as-fabricated multifunctional FSMH could not only exert Fenton reactions in the acidic tumor microenvironment, converting hydrogen peroxide (H2O2) into highly toxic hydroxyl radicals (˙OH), but also effectively consume GSH to attenuate the intracellular oxidative stress. The negative charge of the FSMH nanohydrogel system guarantees its superexcellent stabilization in blood circulation and optimal tumor collection. Subsequently, the surface charge of the endocytosed FSMH was transformed to a positive charge after exposure to the acidic tumor environment, further improving its tumor collection and locally releasing Fe ions and immune adjuvants. Furthermore, Ce6 was released in a pH-responsive manner in the acidic microenvironment. In the presence of near-infrared light, singlet oxygen was produced by the FSMH nanohydrogel system, to ablate tumors and promote the maturation of dendritic cells, achieving the precision-combined strategies effect of CDT, PDT, and immunotherapy.