Tuning the Elasticity of Nanogels Improves Their Circulation Time by Evading Immune Cells

Prachi Desai; Rahul Rimal; Alexandru Florea; Rustam A Gumerov; Marta Santi; Anastasia S Sorokina; Sabri E M Sahnoun; Thorsten Fischer; Felix M Mottaghy; Agnieszka Morgenroth; Ahmed Mourran; Igor I Potemkin; Martin Möller; Smriti Singh

doi:10.1002/anie.202116653

Tuning the Elasticity of Nanogels Improves Their Circulation Time by Evading Immune Cells

Prachi Desai, Rahul Rimal, Alexandru Florea, Rustam A Gumerov, Marta Santi, Anastasia S Sorokina, Sabri E M Sahnoun, Thorsten Fischer, Felix M Mottaghy, Agnieszka Morgenroth, Ahmed Mourran, Igor I Potemkin, Martin Möller, Smriti Singh^*

^*Corresponding author for this work

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

Abstract

Peptide receptor radionuclide therapy is used to treat solid tumors by locally delivering radiation. However, due to nephro- and hepato-toxicity, it is limited by its dosage. To amplify radiation damage to tumor cells, radiolabeled nanogels can be used. We show that by tuning the mechanical properties of nanogels significant enhancement in circulation half-life of the gel could be achieved. We demonstrate why and how small changes in the mechanical properties of the nanogels influence its cellular fate. Nanogels with a storage modulus of 37 kPa were minimally phagocytosed by monocytes and macrophages compared to nanogels with 93 kPa modulus. Using PET/CT a significant difference in the blood circulation time of the nanogels was shown. Computer simulations affirmed the results and predicted the mechanism of cellular uptake of the nanogels. Altogether, this work emphasizes the important role of elasticity even for particles that are inherently soft such as nano- or microgels.

Original language	English
Article number	e202116653
Number of pages	11
Journal	Angewandte Chemie-International Edition
Volume	61
Issue number	20
Early online date	11 Mar 2022
DOIs	https://doi.org/10.1002/anie.202116653
Publication status	Published - 9 May 2022

Keywords

BIODISTRIBUTION
Biodistribution
CLEARANCE
Elasticity
INTERNALIZATION
MACROPHAGE UPTAKE
NANOPARTICLES
Nanogels
OXIDATION
PARTICLES
PHAGOCYTOSIS
Phagocytosis
RADIOLABELED NANOGELS
RIGIDITY
Radiolabeling

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10.1002/anie.202116653Licence: CC BY-NC-ND

Cite this

Desai, P., Rimal, R., Florea, A., Gumerov, R. A., Santi, M., Sorokina, A. S., Sahnoun, S. E. M., Fischer, T., Mottaghy, F. M., Morgenroth, A., Mourran, A., Potemkin, I. I., Möller, M., & Singh, S. (2022). Tuning the Elasticity of Nanogels Improves Their Circulation Time by Evading Immune Cells. Angewandte Chemie-International Edition, 61(20), Article e202116653. https://doi.org/10.1002/anie.202116653

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title = "Tuning the Elasticity of Nanogels Improves Their Circulation Time by Evading Immune Cells",

abstract = "Peptide receptor radionuclide therapy is used to treat solid tumors by locally delivering radiation. However, due to nephro- and hepato-toxicity, it is limited by its dosage. To amplify radiation damage to tumor cells, radiolabeled nanogels can be used. We show that by tuning the mechanical properties of nanogels significant enhancement in circulation half-life of the gel could be achieved. We demonstrate why and how small changes in the mechanical properties of the nanogels influence its cellular fate. Nanogels with a storage modulus of 37 kPa were minimally phagocytosed by monocytes and macrophages compared to nanogels with 93 kPa modulus. Using PET/CT a significant difference in the blood circulation time of the nanogels was shown. Computer simulations affirmed the results and predicted the mechanism of cellular uptake of the nanogels. Altogether, this work emphasizes the important role of elasticity even for particles that are inherently soft such as nano- or microgels.",

keywords = "BIODISTRIBUTION, Biodistribution, CLEARANCE, Elasticity, INTERNALIZATION, MACROPHAGE UPTAKE, NANOPARTICLES, Nanogels, OXIDATION, PARTICLES, PHAGOCYTOSIS, Phagocytosis, RADIOLABELED NANOGELS, RIGIDITY, Radiolabeling",

author = "Prachi Desai and Rahul Rimal and Alexandru Florea and Gumerov, {Rustam A} and Marta Santi and Sorokina, {Anastasia S} and Sahnoun, {Sabri E M} and Thorsten Fischer and Mottaghy, {Felix M} and Agnieszka Morgenroth and Ahmed Mourran and Potemkin, {Igor I} and Martin M{\"o}ller and Smriti Singh",

note = "{\textcopyright} 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.",

year = "2022",

month = may,

day = "9",

doi = "10.1002/anie.202116653",

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Desai, P, Rimal, R, Florea, A, Gumerov, RA, Santi, M, Sorokina, AS, Sahnoun, SEM, Fischer, T, Mottaghy, FM, Morgenroth, A, Mourran, A, Potemkin, II, Möller, M & Singh, S 2022, 'Tuning the Elasticity of Nanogels Improves Their Circulation Time by Evading Immune Cells', Angewandte Chemie-International Edition, vol. 61, no. 20, e202116653. https://doi.org/10.1002/anie.202116653

TY - JOUR

T1 - Tuning the Elasticity of Nanogels Improves Their Circulation Time by Evading Immune Cells

AU - Desai, Prachi

AU - Rimal, Rahul

AU - Florea, Alexandru

AU - Gumerov, Rustam A

AU - Santi, Marta

AU - Sorokina, Anastasia S

AU - Sahnoun, Sabri E M

AU - Fischer, Thorsten

AU - Mottaghy, Felix M

AU - Morgenroth, Agnieszka

AU - Mourran, Ahmed

AU - Potemkin, Igor I

AU - Möller, Martin

AU - Singh, Smriti

PY - 2022/5/9

Y1 - 2022/5/9

N2 - Peptide receptor radionuclide therapy is used to treat solid tumors by locally delivering radiation. However, due to nephro- and hepato-toxicity, it is limited by its dosage. To amplify radiation damage to tumor cells, radiolabeled nanogels can be used. We show that by tuning the mechanical properties of nanogels significant enhancement in circulation half-life of the gel could be achieved. We demonstrate why and how small changes in the mechanical properties of the nanogels influence its cellular fate. Nanogels with a storage modulus of 37 kPa were minimally phagocytosed by monocytes and macrophages compared to nanogels with 93 kPa modulus. Using PET/CT a significant difference in the blood circulation time of the nanogels was shown. Computer simulations affirmed the results and predicted the mechanism of cellular uptake of the nanogels. Altogether, this work emphasizes the important role of elasticity even for particles that are inherently soft such as nano- or microgels.

AB - Peptide receptor radionuclide therapy is used to treat solid tumors by locally delivering radiation. However, due to nephro- and hepato-toxicity, it is limited by its dosage. To amplify radiation damage to tumor cells, radiolabeled nanogels can be used. We show that by tuning the mechanical properties of nanogels significant enhancement in circulation half-life of the gel could be achieved. We demonstrate why and how small changes in the mechanical properties of the nanogels influence its cellular fate. Nanogels with a storage modulus of 37 kPa were minimally phagocytosed by monocytes and macrophages compared to nanogels with 93 kPa modulus. Using PET/CT a significant difference in the blood circulation time of the nanogels was shown. Computer simulations affirmed the results and predicted the mechanism of cellular uptake of the nanogels. Altogether, this work emphasizes the important role of elasticity even for particles that are inherently soft such as nano- or microgels.

KW - BIODISTRIBUTION

KW - Biodistribution

KW - CLEARANCE

KW - Elasticity

KW - INTERNALIZATION

KW - MACROPHAGE UPTAKE

KW - NANOPARTICLES

KW - Nanogels

KW - OXIDATION

KW - PARTICLES

KW - PHAGOCYTOSIS

KW - Phagocytosis

KW - RADIOLABELED NANOGELS

KW - RIGIDITY

KW - Radiolabeling

U2 - 10.1002/anie.202116653

DO - 10.1002/anie.202116653

M3 - Article

C2 - 35274425

SN - 1433-7851

VL - 61

JO - Angewandte Chemie-International Edition

JF - Angewandte Chemie-International Edition

IS - 20

M1 - e202116653

ER -