Issue 21, 2023

Surface chemistry mediates the tumor entrance of nanoparticles probed using single-molecule dual-imaging nanodots

Abstract

The active transport of nanoparticles into solid tumors through transcytosis has been recognized as a promising way to enhance tumor accumulation and penetration, but the effect of the physicochemical properties of nanoparticles remains unclear. Herein, we develop a type of single-molecule dual imaging nanodot by divergent growth of perylenediimide (PDI)-dye-cored polylysine dendrimers and internal orthogonal conjugation of Gd(III)-based macrocyclic probes for fluorescence imaging and magnetic resonance imaging (MRI) of surface chemistry-dependent tumor entrance. The MRI and fluorescence imaging show that sixth-generation nanodots with acetylated (G6-Ac) and oligo ethylene glycol (G6-OEG) surfaces exhibit similar high tumor accumulation but different intratumor distribution. Cellular uptake and transport experiments suggest that G6-Ac nanodots have lower lysosomal entrapment (61% vs. 83%) and a higher exocytotic rate (47% vs. 29%) than G6-OEG. Therefore, G6-Ac is more likely to undergo intercellular transport through cell transcytosis, and is able to reach a tumor area distant from blood vessels, while G6-OEG mainly enters the tumor through enhanced permeability and retention (EPR) effect-based passive transport, and is not able to deliver to distant tumor areas. This study suggests that it is possible to boost the tumor entrance of nanoparticles by engineering surface chemistry for active transport.

Graphical abstract: Surface chemistry mediates the tumor entrance of nanoparticles probed using single-molecule dual-imaging nanodots

Supplementary files

Article information

Article type
Paper
Submitted
13 7 2023
Accepted
20 8 2023
First published
22 8 2023

Biomater. Sci., 2023,11, 7051-7061

Surface chemistry mediates the tumor entrance of nanoparticles probed using single-molecule dual-imaging nanodots

H. Ren, Q. Hu, Y. Sun, X. Zhou, Y. Zhu, Q. Dong, L. Chen, J. Tang, H. Hu, Y. Shen and Z. Zhou, Biomater. Sci., 2023, 11, 7051 DOI: 10.1039/D3BM01171B

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