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Repurposing ICG enables MR/PA imaging signal amplification and iron depletion for iron-overload disorders.

ABSTRACT: Precise and noninvasive theranostic methods to quantify and deplete focal iron are of crucial importance for iron-overload disorders. Here, we developed an indocyanine green (ICG)–based imaging platform to reveal Fe³⁺ in vitro and in vivo. The high sensitivity and specificity of ICG-Fe interaction facilitated MR images with a marked correlation between T₁ signal intensity ratio (T₁SIR) changes and Fe³⁺ concentration in rodent models and humans. On the basis of these findings, a rational design for coordination-driven self-assembly ICG-Lecithin (ICG/Leci) was proposed to determine Fe³⁺. The enhancement of photoacoustic signal at 890 nm with increasing Fe³⁺ concentration showed an over 600% higher linear slope than that of T₁SIR changes in animal models. ICG/Leci also promoted a 100% increase in iron depletion in the liver compared with deferoxamine. The high MR sensitivity and superior photoacoustic contrast, combined with enhanced iron depletion, demonstrate that ICG/Leci is a promising theranostic agent for simultaneous detection and treatment of iron-overload disorders.

SUBMITTER: Lin H

PROVIDER: S-EPMC8682994 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Repurposing ICG enables MR/PA imaging signal amplification and iron depletion for iron-overload disorders.

Lin Huirong H Zhou Yu Y Wang Jiaming J Wang Huimeng H Yao Tianhong T Chen Hu H Zheng Huili H Zhang Yang Y Ren En E Jiang Lai L Chu Chengchao C Chen Xiaoyuan X Mao Jingsong J Wang Fudi F Liu Gang G

Science advances 20211217 51

Precise and noninvasive theranostic methods to quantify and deplete focal iron are of crucial importance for iron-overload disorders. Here, we developed an indocyanine green (ICG)–based imaging platform to reveal Fe3+ in vitro and in vivo. The high sensitivity and specificity of ICG-Fe interaction facilitated MR images with a marked correlation between T1 signal intensity ratio (T1SIR) changes and Fe3+ concentration in rodent models and h ...[more]

PMID: 34919434

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Project description:Hereditary iron overload includes several disorders characterized by iron accumulation in tissues, organs, or even single cells or subcellular compartments. They are determined by mutations in genes directly involved in hepcidin regulation, cellular iron uptake, management and export, iron transport and storage. Systemic forms are characterized by increased serum ferritin with or without high transferrin saturation, and with or without functional iron deficient anemia. Hemochromatosis includes five different genetic forms all characterized by high transferrin saturation and serum ferritin, but with different penetrance and expression. Mutations in HFE, HFE2, HAMP and TFR2 lead to inadequate or severely reduced hepcidin synthesis that, in turn, induces increased intestinal iron absorption and macrophage iron release leading to tissue iron overload. The severity of hepcidin down-regulation defines the severity of iron overload and clinical complications. Hemochromatosis type 4 is caused by dominant gain-of-function mutations of ferroportin preventing hepcidin-ferroportin binding and leading to hepcidin resistance. Ferroportin disease is due to loss-of-function mutation of SLC40A1 that impairs the iron export efficiency of ferroportin, causes iron retention in reticuloendothelial cell and hyperferritinemia with normal transferrin saturation. Aceruloplasminemia is caused by defective iron release from storage and lead to mild microcytic anemia, low serum iron, and iron retention in several organs including the brain, causing severe neurological manifestations. Atransferrinemia and DMT1 deficiency are characterized by iron deficient erythropoiesis, severe microcytic anemia with high transferrin saturation and parenchymal iron overload due to secondary hepcidin suppression. Diagnosis of the different forms of hereditary iron overload disorders involves a sequential strategy that combines clinical, imaging, biochemical, and genetic data. Management of iron overload relies on two main therapies: blood removal and iron chelators. Specific therapeutic options are indicated in patients with atransferrinemia, DMT1 deficiency and aceruloplasminemia.

Dataset Information

Repurposing ICG enables MR/PA imaging signal amplification and iron depletion for iron-overload disorders.

Publications

Repurposing ICG enables MR/PA imaging signal amplification and iron depletion for iron-overload disorders.

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