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Lentinan-functionalized selenium nanosystems with high permeability infiltrate solid tumors by enhancing transcellular transport

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Abstract

The delivery of nanomedicines into internal areas of solid tumors is a great challenge for the design of chemotherapeutic drugs and the realization of their successful application. Herein, we synthesized stable and efficient selenium nanoparticles (SeNPs) with an ideal size and a transcellular transport capability for the penetration and treatment of a solid tumor, utilizing Tw-80 as a dispersing agent and mushroom polysaccharide lentinan (LET) as a decorator. In vitro cellular experiments demonstrated that this nanosystem, LET-Tw-SeNPs, renders significant cellular uptake of HepG2 by receptor-mediated endocytosis and exhibits predominant transcellular transport and penetration capacity towards HepG2 tumor spheroids. Moreover, this therapeutic agent simultaneously inhibits the proliferation and migration of HepG2 cells via a cell cycle arrest pathway. Internalized LET-Tw-SeNPs give rise to the overproduction of intracellular reactive oxygen species (ROS), thus inducing mitochondrial rupture. Meanwhile, pharmacokinetic analysis showed that LET-Tw-SeNPs displayed a long half-life in blood. Altogether, this study demonstrates an inventive strategy for designing nanosystems with high permeability and low blood clearance, in order to achieve efficient in-depth tumor drug delivery and future clinical treatment of solid tumors.

Graphical abstract: Lentinan-functionalized selenium nanosystems with high permeability infiltrate solid tumors by enhancing transcellular transport

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Supplementary files

Article information


Submitted
17 Mar 2020
Accepted
18 Jun 2020
First published
19 Jun 2020

Nanoscale, 2020, Advance Article
Article type
Paper

Lentinan-functionalized selenium nanosystems with high permeability infiltrate solid tumors by enhancing transcellular transport

F. Yang, J. Huang, H. Liu, W. Lin, X. Li, X. Zhu and T. Chen, Nanoscale, 2020, Advance Article , DOI: 10.1039/D0NR02171G

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