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

Aziz B. Mirkasymov; Ivan V. Zelepukin; Ilya N. Ivanov; Iaroslav B. Belyaev; Dzhuliia Sh. Dzhalilova; Daria B. Trushina; Alexey V. Yaremenko; Vsevolod Yu. Ivanov; Maxim P. Nikitin; Petr I. Nikitin; Andrei V. Zvyagin; Sergey M. Deyev

doi:10.1016/j.ijpharm.2022.121795

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

Aziz B. Mirkasymov^*, Ivan V. Zelepukin, Ilya N. Ivanov, Iaroslav B. Belyaev, Dzhuliia Sh. Dzhalilova, Daria B. Trushina, Alexey V. Yaremenko, Vsevolod Yu. Ivanov, Maxim P. Nikitin, Petr I. Nikitin, Andrei V. Zvyagin, Sergey M. Deyev

^*Corresponding author for this work

ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP)

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

Abstract

The rapid elimination of systemically administered drug nanocarriers by the mononuclear phagocyte system (MPS) compromises nanomedicine delivery efficacy. To mitigate this problem, an approach to block the MPS has been introduced and implemented by intravenous pre-administering blocker nanoparticles. The required large doses of blocker nanoparticles appeared to burden the MPS, raising toxicity concerns. To alleviate the toxicity issues in MPS blockade, we propose an intrinsically biocompatible blocker, ferrihydrite – a metabolite ubiquitous in a biological organism. Ferrihydrite particles were synthesized to mimic endogenous ferritin-bound iron. Ferrihydrite surface coating with carboxymethyl-dextran was found to improve MPS blockade dramatically with a 9-fold prolongation of magnetic nanoparticle circulation in the bloodstream and a 24-fold increase in the tumor targeted delivery. The administration of high doses of ferrihydrite caused low toxicity with a rapid recovery of toxicological parameters after 3 days. We believe that ferrihydrite particles coated with carboxymethyl-dextran represent superior blocking biomaterial with enviable biocompatibility.

Original language	English
Article number	121795
Pages (from-to)	1-10
Number of pages	10
Journal	International Journal of Pharmaceutics
Volume	621
DOIs	https://doi.org/10.1016/j.ijpharm.2022.121795
Publication status	Published - 10 Jun 2022

Keywords

Biodistribution
Ferrihydrite
Magnetic nanoparticles
Mononuclear phagocyte system
Pharmacokinetics
Toxicity

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10.1016/j.ijpharm.2022.121795

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Mirkasymov, A. B., Zelepukin, I. V., Ivanov, I. N., Belyaev, I. B., Sh. Dzhalilova, D., Trushina, D. B., Yaremenko, A. V., Yu. Ivanov, V., Nikitin, M. P., Nikitin, P. I., Zvyagin, A. V., & Deyev, S. M. (2022). Macrophage blockade using nature-inspired ferrihydrite for enhanced nanoparticle delivery to tumor. International Journal of Pharmaceutics, 621, 1-10. Article 121795. https://doi.org/10.1016/j.ijpharm.2022.121795

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abstract = "The rapid elimination of systemically administered drug nanocarriers by the mononuclear phagocyte system (MPS) compromises nanomedicine delivery efficacy. To mitigate this problem, an approach to block the MPS has been introduced and implemented by intravenous pre-administering blocker nanoparticles. The required large doses of blocker nanoparticles appeared to burden the MPS, raising toxicity concerns. To alleviate the toxicity issues in MPS blockade, we propose an intrinsically biocompatible blocker, ferrihydrite – a metabolite ubiquitous in a biological organism. Ferrihydrite particles were synthesized to mimic endogenous ferritin-bound iron. Ferrihydrite surface coating with carboxymethyl-dextran was found to improve MPS blockade dramatically with a 9-fold prolongation of magnetic nanoparticle circulation in the bloodstream and a 24-fold increase in the tumor targeted delivery. The administration of high doses of ferrihydrite caused low toxicity with a rapid recovery of toxicological parameters after 3 days. We believe that ferrihydrite particles coated with carboxymethyl-dextran represent superior blocking biomaterial with enviable biocompatibility.",

keywords = "Biodistribution, Ferrihydrite, Magnetic nanoparticles, Mononuclear phagocyte system, Pharmacokinetics, Toxicity",

author = "Mirkasymov, {Aziz B.} and Zelepukin, {Ivan V.} and Ivanov, {Ilya N.} and Belyaev, {Iaroslav B.} and {Sh. Dzhalilova}, Dzhuliia and Trushina, {Daria B.} and Yaremenko, {Alexey V.} and {Yu. Ivanov}, Vsevolod and Nikitin, {Maxim P.} and Nikitin, {Petr I.} and Zvyagin, {Andrei V.} and Deyev, {Sergey M.}",

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doi = "10.1016/j.ijpharm.2022.121795",

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Mirkasymov, AB, Zelepukin, IV, Ivanov, IN, Belyaev, IB, Sh. Dzhalilova, D, Trushina, DB, Yaremenko, AV, Yu. Ivanov, V, Nikitin, MP, Nikitin, PI, Zvyagin, AV & Deyev, SM 2022, 'Macrophage blockade using nature-inspired ferrihydrite for enhanced nanoparticle delivery to tumor', International Journal of Pharmaceutics, vol. 621, 121795, pp. 1-10. https://doi.org/10.1016/j.ijpharm.2022.121795

TY - JOUR

T1 - Macrophage blockade using nature-inspired ferrihydrite for enhanced nanoparticle delivery to tumor

AU - Mirkasymov, Aziz B.

AU - Zelepukin, Ivan V.

AU - Ivanov, Ilya N.

AU - Belyaev, Iaroslav B.

AU - Sh. Dzhalilova, Dzhuliia

AU - Trushina, Daria B.

AU - Yaremenko, Alexey V.

AU - Yu. Ivanov, Vsevolod

AU - Nikitin, Maxim P.

AU - Nikitin, Petr I.

AU - Zvyagin, Andrei V.

AU - Deyev, Sergey M.

PY - 2022/6/10

Y1 - 2022/6/10

N2 - The rapid elimination of systemically administered drug nanocarriers by the mononuclear phagocyte system (MPS) compromises nanomedicine delivery efficacy. To mitigate this problem, an approach to block the MPS has been introduced and implemented by intravenous pre-administering blocker nanoparticles. The required large doses of blocker nanoparticles appeared to burden the MPS, raising toxicity concerns. To alleviate the toxicity issues in MPS blockade, we propose an intrinsically biocompatible blocker, ferrihydrite – a metabolite ubiquitous in a biological organism. Ferrihydrite particles were synthesized to mimic endogenous ferritin-bound iron. Ferrihydrite surface coating with carboxymethyl-dextran was found to improve MPS blockade dramatically with a 9-fold prolongation of magnetic nanoparticle circulation in the bloodstream and a 24-fold increase in the tumor targeted delivery. The administration of high doses of ferrihydrite caused low toxicity with a rapid recovery of toxicological parameters after 3 days. We believe that ferrihydrite particles coated with carboxymethyl-dextran represent superior blocking biomaterial with enviable biocompatibility.

AB - The rapid elimination of systemically administered drug nanocarriers by the mononuclear phagocyte system (MPS) compromises nanomedicine delivery efficacy. To mitigate this problem, an approach to block the MPS has been introduced and implemented by intravenous pre-administering blocker nanoparticles. The required large doses of blocker nanoparticles appeared to burden the MPS, raising toxicity concerns. To alleviate the toxicity issues in MPS blockade, we propose an intrinsically biocompatible blocker, ferrihydrite – a metabolite ubiquitous in a biological organism. Ferrihydrite particles were synthesized to mimic endogenous ferritin-bound iron. Ferrihydrite surface coating with carboxymethyl-dextran was found to improve MPS blockade dramatically with a 9-fold prolongation of magnetic nanoparticle circulation in the bloodstream and a 24-fold increase in the tumor targeted delivery. The administration of high doses of ferrihydrite caused low toxicity with a rapid recovery of toxicological parameters after 3 days. We believe that ferrihydrite particles coated with carboxymethyl-dextran represent superior blocking biomaterial with enviable biocompatibility.

KW - Biodistribution

KW - Ferrihydrite

KW - Magnetic nanoparticles

KW - Mononuclear phagocyte system

KW - Pharmacokinetics

KW - Toxicity

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DO - 10.1016/j.ijpharm.2022.121795

M3 - Article

C2 - 35526695

AN - SCOPUS:85129757009

SN - 0378-5173

VL - 621

SP - 1

EP - 10

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

M1 - 121795

ER -

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

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Keywords

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