Magnetic Resonance Imaging Nanoprobe Quantifies Nitric Oxide for Evaluating M1/M2 Macrophage Polarization and Prognosis of Cancer Treatments

Liu, Xiaomin; Wang, Mingkun; Jiang, Yichao; Zhang, Xinyi; Shi, Changrong; Zeng, Fantian; Qin, Yatong; Ye, Jinmin; Hu, Jiaying; Zhou, Zijian

doi:10.1021/acsnano.3c05627

Cited by 15 publications

(4 citation statements)

References 56 publications

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“…An ultrasmall paramagnetic iron oxide-based nanoprobe was modified and the aggregation of the nanoprobe could be triggered with an increase in the nitric oxide concentration. Comparing the treatment effects in a 4T1-tumor bearing murine model at three radiation doses (0 Gy, 0.5 Gy, and 3.0 Gy), a similar trend was observed for the ΔSNR tumor in the T1 and T2 settings and the M1/M2 ratios in these groups: a significant change in the imaging contrast and an increase in the M1/M2 ratios in the 3.0 Gy-irradiated group compared to those in the non-treated group and the 0.5 Gy-treated group, while no statistical difference in both the imaging contrast and the M1/M2 ratio between the non-treated group and the 0.5 Gy-treated group ( Figure 6 C ) 147 .…”

Section: Biomarker-driven Molecular Imaging Probes In Radiotherapy Wo...mentioning

confidence: 90%

“…C) Nitric oxide-triggered self-assembly of the USPIO@OMG nanoprobe for evaluating macrophage polarization during radiotherapy: (i) chemical principle for aggregation of the nanoprobe; (ii) TEM images to confirm the aggregation status of the nanoprobe in M1 macrophages; (iii) CLSM images of tumor slices from two radiation dose-treated groups, red CD206 signal indicates M2 macrophages while the green iNOS signal represents M1 macrophages; (iv) The T2 MRI signal changes in different groups. Adapted with permission 147 . Copyright 2023 American Chemical Society.…”

Section: Figurementioning

confidence: 99%

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Biomarker-driven molecular imaging probes in radiotherapy

Li,

Gong,

Luo

2024

Theranostics

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Background: Biomarker-driven molecular imaging has emerged as an integral part of cancer precision radiotherapy. The use of molecular imaging probes, including nanoprobes, have been explored in radiotherapy imaging to precisely and noninvasively monitor spatiotemporal distribution of biomarkers, potentially revealing tumor-killing mechanisms and therapy-induced adverse effects during radiation treatment. Methods: We summarized literature reports from preclinical studies and clinical trials, which cover two main parts: 1) Clinically-investigated and emerging imaging biomarkers associated with radiotherapy, and 2) instrumental roles, functions, and activatable mechanisms of molecular imaging probes in the radiotherapy workflow. In addition, reflection and future perspectives are proposed. Results: Numerous imaging biomarkers have been continuously explored in decades, while few of them have been successfully validated for their correlation with radiotherapeutic outcomes and/or radiation-induced toxicities. Meanwhile, activatable molecular imaging probes towards the emerging biomarkers have exhibited to be promising in animal or small-scale human studies for precision radiotherapy. Conclusion: Biomarker-driven molecular imaging probes are essential for precision radiotherapy. Despite very inspiring preliminary results, validation of imaging biomarkers and rational design strategies of probes await robust and extensive investigations. Especially, the correlation between imaging biomarkers and radiotherapeutic outcomes/toxicities should be established through multi-center collaboration involving a large cohort of patients.

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Section: Biomarker-driven Molecular Imaging Probes In Radiotherapy Wo...mentioning

confidence: 90%

Section: Figurementioning

confidence: 99%

Biomarker-driven molecular imaging probes in radiotherapy

Li,

Gong,

Luo

2024

Theranostics

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“…This enhances the expression of genes supporting glycolytic metabolism in this cell subtype. Furthermore, they express iNOS to produce NO from arginine, a key mediator in inflammation regulation [ 158 , 161 , 162 ]. M2 macrophages also heavily rely on high glycolytic activity and exhibit high lactate secretion similar to the M1 phenotype.…”

Section: Regulation Of Macrophage Polarizationmentioning

confidence: 99%

Deciphering the performance of macrophages in tumour microenvironment: a call for precision immunotherapy

Toledo,

Zhu Chen,

Paniagua-Sancho

et al. 2024

J Hematol Oncol

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Macrophages infiltrating tumour tissues or residing in the microenvironment of solid tumours are known as tumour-associated macrophages (TAMs). These specialized immune cells play crucial roles in tumour growth, angiogenesis, immune regulation, metastasis, and chemoresistance. TAMs encompass various subpopulations, primarily classified into M1 and M2 subtypes based on their differentiation and activities. M1 macrophages, characterized by a pro-inflammatory phenotype, exert anti-tumoural effects, while M2 macrophages, with an anti-inflammatory phenotype, function as protumoural regulators. These highly versatile cells respond to stimuli from tumour cells and other constituents within the tumour microenvironment (TME), such as growth factors, cytokines, chemokines, and enzymes. These stimuli induce their polarization towards one phenotype or another, leading to complex interactions with TME components and influencing both pro-tumour and anti-tumour processes.This review comprehensively and deeply covers the literature on macrophages, their origin and function as well as the intricate interplay between macrophages and the TME, influencing the dual nature of TAMs in promoting both pro- and anti-tumour processes. Moreover, the review delves into the primary pathways implicated in macrophage polarization, examining the diverse stimuli that regulate this process. These stimuli play a crucial role in shaping the phenotype and functions of macrophages. In addition, the advantages and limitations of current macrophage based clinical interventions are reviewed, including enhancing TAM phagocytosis, inducing TAM exhaustion, inhibiting TAM recruitment, and polarizing TAMs towards an M1-like phenotype. In conclusion, while the treatment strategies targeting macrophages in precision medicine show promise, overcoming several obstacles is still necessary to achieve an accessible and efficient immunotherapy.

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“…Extremely small iron oxide nanoparticles (ESIONPs) are a T 1 -type CA with intriguing property, wherein they can switch to a T 2 -type one when aggregating due to magnetic coupling. − Obviously, utilizing the contrast enhancement transition between T 1 and T 2 of ESIONPs to design stimuli-responsive smart CAs can greatly enhance tumor specificity and reduce background signal . At present, various T 1 –T 2 and T 2 –T 1 switchable CAs have been developed for the diagnosis of brain diseases , and tumors. ,, For instance, Liu et al reported o-phenylenediamine and mannose-functionalized ESIONPs, which could assemble in response to the biomarker NO from the transition of M2 to M1 macrophages, offering insights into tumor macrophage M1/M2 polarization for precisely evaluating cancer prognosis . Moreover, previous work in our group utilized 4,4′-azodianiline as a cross-linker to obtain an ESIONP nanocluster (EAmP), which could respond to the tumor hypoxic microenvironment and decompose into dispersed ESIONPs, leading to a switch from T 2 to T 1 contrast enhancement for accurate tumor diagnosis .…”

mentioning

confidence: 99%

A “Dual-Key-and-Lock” MRI Contrast Agent with T₁–T₂ Switchable Function for Accurate Diagnosis of Tumors

Lu,

Yan,

et al. 2024

Nano Lett.

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Extremely small iron oxide nanoparticle (ESIONP)based stimuli-responsive switchable MRI contrast agents (CAs) show great promise for accurate detection of tumors due to their outstanding advantages of high specificity and low background signal. However, currently developed ESIONP-based switchable CAs often suffer single-biomarker-induced responses, which lack absolute specificity to pathological tissues, potentially diminishing diagnostic accuracy. In this study, weak acidity and hypoxia, two of the most remarkable characteristics of tumors, are introduced as dual biomarker stimuli to construct an ESIONP-based switchable MRI CA (DKL-CA), with its signal switch controlled by a "dualkey-and-lock" strategy. Only when DKL-CA is exposed to a coexisting weakly acidic and hypoxic environment can monodispersed ESIONPs form nanoclusters, thereby realizing a switch from the T 1 to T 2 contrast. Moreover, DKL-CA exhibits favorable biosafety and the capacity for precise tumor diagnosis in tumor-bearing mice. Overall, DKL-CA paves the way for designing highly accurate ESIONP-based MRI CAs for tumor diagnosis.

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Magnetic Resonance Imaging Nanoprobe Quantifies Nitric Oxide for Evaluating M1/M2 Macrophage Polarization and Prognosis of Cancer Treatments

Cited by 15 publications

References 56 publications

Biomarker-driven molecular imaging probes in radiotherapy

Biomarker-driven molecular imaging probes in radiotherapy

Deciphering the performance of macrophages in tumour microenvironment: a call for precision immunotherapy

A “Dual-Key-and-Lock” MRI Contrast Agent with T₁–T₂ Switchable Function for Accurate Diagnosis of Tumors

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Magnetic Resonance Imaging Nanoprobe Quantifies Nitric Oxide for Evaluating M1/M2 Macrophage Polarization and Prognosis of Cancer Treatments

Cited by 15 publications

References 56 publications

Biomarker-driven molecular imaging probes in radiotherapy

Biomarker-driven molecular imaging probes in radiotherapy

Deciphering the performance of macrophages in tumour microenvironment: a call for precision immunotherapy

A “Dual-Key-and-Lock” MRI Contrast Agent with T1–T2 Switchable Function for Accurate Diagnosis of Tumors

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Product

Resources

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A “Dual-Key-and-Lock” MRI Contrast Agent with T₁–T₂ Switchable Function for Accurate Diagnosis of Tumors