Macrophage blockade using nature-inspired ferrihydrite for enhanced nanoparticle delivery to tumor

Mirkasymov, Aziz B.; Zelepukin, Ivan V.; Ivanov, Ilya N.; Belyaev, Iaroslav B.; Джалилова, Д. Ш.; Trushina, Daria B.; Yaremenko, A. V.; Ivanov, Vsevolod Yu.; Nikitin, Maxim P.; Никитин, П. И.; Zvyagin, Andrei V.; Deyev, Sergey M.

doi:10.1016/j.ijpharm.2022.121795

Cited by 7 publications

(4 citation statements)

References 53 publications

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“…Every published study included the systemic toxicity assay by histological or biochemical methods. Despite reported slight elevation in ALT levels immediately after the treatment, in general they did not induce any significant long-term inflammatory, dystrophic, or necrotic changes in major organs when used as a blockers 63 , 64 , 80 . However, in short-term iron-based nanoparticles stimulated the growth of macrophage population, which might have been the response to the iron catabolism 111 .…”

Section: Introductionmentioning

confidence: 86%

“…Therefore, the MPS blockade facilitates transport of therapeutic nanoparticles from liver to other macrophage-rich organs such as spleen and bone marrow. Spillover effect is observed for different blocking agents, including nanoparticles, polymers, cells, and molecular agents such as liposomal clodronate and gadolinium chloride 43 , 64 , 69 , 100 .…”

Section: Introductionmentioning

confidence: 99%

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Rediscovery of mononuclear phagocyte system blockade for nanoparticle drug delivery

Zelepukin,

Shevchenko,

Deyev

2024

Nat Commun

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Rapid uptake of nanoparticles by mononuclear phagocyte system (MPS) significantly hampers their therapeutic efficacy. Temporal MPS blockade is one of the few ways to overcome this barrier – the approach rediscovered many times under different names but never extensively used in clinic. Using meta-analysis of the published data we prove the efficacy of this technique for enhancing particle circulation in blood and their delivery to tumours, describe a century of its evolution and potential combined mechanism behind it. Finally, we discuss future directions of the research focusing on the features essential for successful clinical translation of the method.

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Section: Introductionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Rediscovery of mononuclear phagocyte system blockade for nanoparticle drug delivery

Zelepukin,

Shevchenko,

Deyev

2024

Nat Commun

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“…Initially, 300 µg of MPs were administered into retroorbital sinus of animals (7 groups, n = 3 mice in each). To measure the MP biodegradation non-invasively, an MPQ detection coil of 20 mm in diameter [ 7 , 9 , 22 ] was attached to the region near the mice liver and spleen, and the magnetic signal was recorded for 10 s.…”

Section: Methodsmentioning

confidence: 99%

Influence of magnetic nanoparticle biotransformation on contrasting efficiency and iron metabolism

et al. 2022

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Magnetic nanoparticles are widely used in biomedicine for MRI imaging and anemia treatment. The aging of these nanomaterials in vivo may lead to gradual diminishing of their contrast properties and inducing toxicity. Here, we describe observation of the full lifecycle of 40-nm magnetic particles from their injection to the complete degradation in vivo and associated impact on the organism. We found that in 2 h the nanoparticles were eliminated from the bloodstream, but their initial biodistribution changed over time. In 1 week, a major part of the nanoparticles was transferred to the liver and spleen, where they degraded with a half-life of 21 days. MRI and a magnetic spectral approach revealed preservation of contrast in these organs for more than 1 month. The particle degradation led to the increased number of red blood cells and blood hemoglobin level due to released iron without causing any toxicity in tissues. We also observed an increase in gene expression level of Fe-associated proteins such as transferrin, DMT1, and ferroportin in the liver in response to the iron particle degradation. A deeper understanding of the organism response to the particle degradation can bring new directions to the field of MRI contrast agent design.

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“…The non-specific deposition of 188 Re in the liver and spleen led to exposure of healthy tissues to damaging radiation. Nevertheless, particle accumulation in these organs can be delayed or reduced in further studies by various strategies, including nanoparticle modification with 'stealth' polymers, cell membranes or targeted moieties [48,49], as well as preliminary blockade of macrophages by low-toxic agents [50,51].…”

Section: Mof Labeling With 188 Rementioning

confidence: 99%

Nanoparticles based on MIL-101 metal-organic frameworks as efficient carriers of therapeutic ¹⁸⁸Re radionuclide for nuclear medicine

Belyaev,

Zelepukin,

Tishchenko

et al. 2023

Nanotechnology

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Nuclear medicine presents one of the most promising modalities for efficient non-invasive treatment of a variety of cancers, but the application of radionuclides in cancer therapy and diagnostics is severely limited by their nonspecific tissue accumulation and poor biocompatibility. Here, we explore the use of nanosized metal-organic frameworks (MOFs) as carriers of radionuclides to order to improve their delivery to tumour. To demonstrate the concept, we prepared polymer-coated MIL-101(Cr)-NH2 MOFs and conjugated them with clinically utilized radionuclide 188Re. The nanoparticles demonstrated high loading efficacy of radionuclide reaching specific activity of 49 MBq/mg. Pharmacokinetics of loaded MOFs was investigated in mice bearing colon adenocarcinoma. The biological half-life of the radionuclide in blood was 13.7 ± 3.5 h, while the nanoparticles offered the ability to passively accumulate and retain the radionuclide in the tumour. The radionuclide delivery with MOFs led to a significant decrease of radioactivity uptake by the thyroid gland and stomach as compared with perrhenate salt injection, which is beneficial for reducing the side toxicity of nuclear therapy. The reported data on the functionalization and pharmacokinetics of MIL-101(Cr)-NH2 for radionuclide delivery unveils the promising potential of these MOFs for nuclear medicine.

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Macrophage blockade using nature-inspired ferrihydrite for enhanced nanoparticle delivery to tumor

Cited by 7 publications

References 53 publications

Rediscovery of mononuclear phagocyte system blockade for nanoparticle drug delivery

Rediscovery of mononuclear phagocyte system blockade for nanoparticle drug delivery

Influence of magnetic nanoparticle biotransformation on contrasting efficiency and iron metabolism

Nanoparticles based on MIL-101 metal-organic frameworks as efficient carriers of therapeutic ¹⁸⁸Re radionuclide for nuclear medicine

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Macrophage blockade using nature-inspired ferrihydrite for enhanced nanoparticle delivery to tumor

Cited by 7 publications

References 53 publications

Rediscovery of mononuclear phagocyte system blockade for nanoparticle drug delivery

Rediscovery of mononuclear phagocyte system blockade for nanoparticle drug delivery

Influence of magnetic nanoparticle biotransformation on contrasting efficiency and iron metabolism

Nanoparticles based on MIL-101 metal-organic frameworks as efficient carriers of therapeutic 188Re radionuclide for nuclear medicine

Contact Info

Product

Resources

About

Nanoparticles based on MIL-101 metal-organic frameworks as efficient carriers of therapeutic ¹⁸⁸Re radionuclide for nuclear medicine