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Evaluation of Nanoparticle Uptake in Tumors in Real Time Using Intravital Imaging

Evaluation of Nanoparticle Uptake in Tumors in Real Time Using Intravital Imaging

Published on: June 21, 2011

The entry of nanoparticles into solid tumours.

Shrey Sindhwani¹, Abdullah Muhammad Syed¹, Jessica Ngai^1,2

¹Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.

Nature Materials

|January 15, 2020

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Summary

This summary is machine-generated.

Nanoparticles do not primarily enter tumors through gaps between endothelial cells. Instead, an active process through these cells facilitates nanoparticle entry, challenging current cancer nanomedicine strategies.

Area of Science:

Oncology
Nanomedicine
Cell Biology

Background:

The established concept in cancer nanomedicine posits that nanoparticles extravasate through inter-endothelial gaps in tumor vasculature.
These gaps, measuring up to 2,000 nm, were thought to facilitate nanoparticle access to the tumor microenvironment.
This paradigm has driven the development of nanoparticles for solid tumor treatment.

Purpose of the Study:

To investigate the primary mechanism of nanoparticle transport into solid tumors.
To challenge the prevailing hypothesis that inter-endothelial gaps are the main route for nanoparticle extravasation.
To identify alternative pathways for nanoparticle delivery in cancer therapy.

Main Methods:

Analysis of four distinct mouse models with solid tumors.

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Inclusion of three different human tumor types for broader relevance.

Application of mathematical simulation and modeling.

Utilisation of two distinct imaging techniques for nanoparticle tracking.

Main Results:

Contrary to the established view, inter-endothelial gaps are not the primary pathway for nanoparticle entry into tumors.
Up to 97% of nanoparticles were found to enter tumors via an active process mediated by endothelial cells.
This finding was consistent across multiple models and techniques.

Conclusions:

The current understanding of nanoparticle transport in cancer nanomedicine requires revision.
Active endothelial cell-mediated transport is the dominant mechanism for nanoparticle entry into solid tumors.
Understanding and targeting these active pathways holds potential for enhancing nanoparticle accumulation in tumors.