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

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 properti...

Full description

Saved in:
Bibliographic Details
Published in:Angewandte Chemie International Edition 2022-05, Vol.61 (20), p.e202116653-n/a
Main Authors: Desai, Prachi, Rimal, Rahul, Florea, Alexandru, Gumerov, Rustam A., Santi, Marta, Sorokina, Anastasia S., Sahnoun, Sabri E. M., Fischer, Thorsten, Mottaghy, Felix M., Morgenroth, Agnieszka, Mourran, Ahmed, Potemkin, Igor I., Möller, Martin, Singh, Smriti
Format: Article
Language:English
Subjects:
Biodistribution
Blood circulation
Blood Circulation Time
Elasticity
Immune system
Macrophages
Mathematical models
Mechanical properties
Microgels
Monocytes
Nanogels
Phagocytosis
Positron Emission Tomography Computed Tomography
Radiation
Radiation damage
Radiation dosage
Radiation therapy
Radioisotopes
Radiolabeling
Solid tumors
Storage modulus
Toxicity
Tumor cells
Tumors
Tuning
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. Small changes in the elasticity of the inherently soft radiolabeled nanogels show major differences in its in vivo circulation half‐life. Longer circulation life renders a higher possibility for nanogels to accumulate in the tumor microenvironment by enhanced permeation and retention effect.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.202116653