Iron-Containing Protein-Mimic Supramolecular Iron Delivery Systems for Ferroptosis Tumor Therapy

Abstract

Ferroptosis provides an innovative theoretical basis and method for tumor therapy but is limited by the low efficiency of conventional iron delivery systems. Herein, an efficient supramolecular iron delivery system (SIDS) is demonstrated upon the hydrolysis of FeCl3, condensation of amino acids, and self-assembly of iron-containing components. The as-assembled SIDS possesses a shuttle-like core/shell structure with β-FeOOH as the core and Fe3+/polyamino acid coordinated networks as shells. The iron content of SIDS is up to 42 wt %, which is greatly higher than that of ferritin. The iron-containing protein-mimic structure and shuttle-like morphology of SIDS facilitate tumor accumulation and cell internalization. Once exposed to the tumor microenvironment with overexpressed glutathione (GSH), the SIDS will disassemble, accompanied by the depletion of GSH and the release of Fe2+, leading to dual amplified ferroptosis. Primary studies indicate that SIDS exhibits outstanding antitumor efficacy on bladder cancer.

Aptamer–Protein Interactions: From Regulation to Biomolecular Detection

“…413−415 Metal ions can be contained in proteins or aptamers, driving the metal chelation between aptamers and proteins to promote their binding. 414,416 Thus, a series of analytical strategies based on metal chelation have been established for biomolecular detection. The zinc finger structure is a Zn 2+ -dependent folded finger-like domain.…”

“…In recent years, research on the formation mechanism of metal–amino acid–nucleoside ternary compounds facilitate the in-depth understanding of aptamer–protein chelation mediated by metal ions. − Metal ions can be contained in proteins or aptamers, driving the metal chelation between aptamers and proteins to promote their binding. , Thus, a series of analytical strategies based on metal chelation have been established for biomolecular detection. The zinc finger structure is a Zn 2+ -dependent folded finger-like domain. , Proteins with zinc finger structures (zinc-finger proteins) are usually functional proteins involved in the regulation of gene expression. , For instance, as a key biomarker of human immunodeficiency virus type 1 (HIV-1), nucleocapsid protein 7 (NCp7) contains two zinc-finger structures and plays a critical role in viral reverse transcription. , To achieve high-sensitivity detection of NCp7, an aptamer tightly bound to NCp7 was developed, and their interaction was found to be strongly dependent on Zn 2+ . , Based on the specific interactions between NCp7 and its aptamer, Niedzwiecki et al combined the nanopore technique with the resistive-pulse technique for NCp7 quantification .…”

Cu2+–Citrate–Chitosan Complex Nanoparticles for the Chemodynamic Therapy of Lung Cancer

“…In recent years, with the rapid development of nanotechnology, nanomedicine has gained significant attention due to its unique properties. Especially, the emergence of nanomedicine has provided new options for the treatment of tumors. − Nanomedicine for lung cancer diagnosis and therapy has also been extensively studied, ,− exhibiting notable advantages such as high safety, specificity, and convenience compared to traditional treatments. − Chemodynamic therapy (CDT) is an emerging cancer treatment strategy that was first proposed in 2016 . In the acidic tumor microenvironment (TME), it utilizes the Fenton reaction or Fenton-like reactions to convert the overexpressed hydrogen peroxide (H 2 O 2 ) into highly cytotoxic hydroxyl radical (•OH) species to kill cancer cells .…”

Resveratrol-Coated Gold Nanoflowers for CT Imaging and Apoptosis/Photothermal Synergistic Therapy of Malignant Melanoma

“…In the past decade, nanoscience and nanotechnology have developed rapidly and brought about many positive effects on human life. − In the field of biomedicine, nanomaterial-based photothermal therapy (PTT), , photodynamic therapy (PDT), , sonodynamic therapy (SDT), , chemodynamic therapy (CDT), − immunotherapy, , and other new methods , have greatly promoted the development of tumor treatment methodology and provided more possibilities for tumor therapy …”