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Intravital Microscopy Reveals Endothelial Transcytosis Contributing to Significant Tumor Accumulation of Albumin Nanoparticles
The principle of enhanced permeability and retention (EPR) effect has been used to design anti-cancer nanomedicines over decades. However, it is being challenged due to the poor clinical outcome of nanoparticles and controversial physiological foundation. Herein, we use a near-infrared-II (1000–1700...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9960641/ https://www.ncbi.nlm.nih.gov/pubmed/36839841 http://dx.doi.org/10.3390/pharmaceutics15020519 |
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author | Wei, Guoguang Zhang, Sihang Yu, Sheng Lu, Wei |
author_facet | Wei, Guoguang Zhang, Sihang Yu, Sheng Lu, Wei |
author_sort | Wei, Guoguang |
collection | PubMed |
description | The principle of enhanced permeability and retention (EPR) effect has been used to design anti-cancer nanomedicines over decades. However, it is being challenged due to the poor clinical outcome of nanoparticles and controversial physiological foundation. Herein, we use a near-infrared-II (1000–1700 nm, NIR-II) fluorescence probe BPBBT to investigate the pathway for the entry of human serum albumin-bound nanoparticles (BPBBT-HSA NPs) into tumor compared with BPBBT micelles with phospholipid-poly (ethylene glycol) of the similar particle size about 110 nm. The plasma elimination half-life of BPBBT micelles was 2.8-fold of that of BPBBT-HSA NPs. However, the area under the BPBBT concentration in tumor-time curve to 48 h post-injection (AUC(tumor0→48h)) of BPBBT-HSA NPs was 7.2-fold of that of BPBBT micelles. The intravital NIR-II fluorescence microscopy revealed that BPBBT-HSA NPs but not BPBBT micelles were transported from the tumor vasculature into tumor parenchyma with high efficiency, and endocytosed by the tumor cells within 3 h post-injection in vivo. This effect was blocked by cross-linking BPBBT-HSA NPs to denature HSA, resulting in the AUC(tumor0→48h) decreased to 22% of that of BPBBT-HSA NPs. Our results demonstrated that the active process of endothelial transcytosis is the dominant pathway for albumin-bound nanoparticles’ entry into tumor. |
format | Online Article Text |
id | pubmed-9960641 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99606412023-02-26 Intravital Microscopy Reveals Endothelial Transcytosis Contributing to Significant Tumor Accumulation of Albumin Nanoparticles Wei, Guoguang Zhang, Sihang Yu, Sheng Lu, Wei Pharmaceutics Article The principle of enhanced permeability and retention (EPR) effect has been used to design anti-cancer nanomedicines over decades. However, it is being challenged due to the poor clinical outcome of nanoparticles and controversial physiological foundation. Herein, we use a near-infrared-II (1000–1700 nm, NIR-II) fluorescence probe BPBBT to investigate the pathway for the entry of human serum albumin-bound nanoparticles (BPBBT-HSA NPs) into tumor compared with BPBBT micelles with phospholipid-poly (ethylene glycol) of the similar particle size about 110 nm. The plasma elimination half-life of BPBBT micelles was 2.8-fold of that of BPBBT-HSA NPs. However, the area under the BPBBT concentration in tumor-time curve to 48 h post-injection (AUC(tumor0→48h)) of BPBBT-HSA NPs was 7.2-fold of that of BPBBT micelles. The intravital NIR-II fluorescence microscopy revealed that BPBBT-HSA NPs but not BPBBT micelles were transported from the tumor vasculature into tumor parenchyma with high efficiency, and endocytosed by the tumor cells within 3 h post-injection in vivo. This effect was blocked by cross-linking BPBBT-HSA NPs to denature HSA, resulting in the AUC(tumor0→48h) decreased to 22% of that of BPBBT-HSA NPs. Our results demonstrated that the active process of endothelial transcytosis is the dominant pathway for albumin-bound nanoparticles’ entry into tumor. MDPI 2023-02-03 /pmc/articles/PMC9960641/ /pubmed/36839841 http://dx.doi.org/10.3390/pharmaceutics15020519 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wei, Guoguang Zhang, Sihang Yu, Sheng Lu, Wei Intravital Microscopy Reveals Endothelial Transcytosis Contributing to Significant Tumor Accumulation of Albumin Nanoparticles |
title | Intravital Microscopy Reveals Endothelial Transcytosis Contributing to Significant Tumor Accumulation of Albumin Nanoparticles |
title_full | Intravital Microscopy Reveals Endothelial Transcytosis Contributing to Significant Tumor Accumulation of Albumin Nanoparticles |
title_fullStr | Intravital Microscopy Reveals Endothelial Transcytosis Contributing to Significant Tumor Accumulation of Albumin Nanoparticles |
title_full_unstemmed | Intravital Microscopy Reveals Endothelial Transcytosis Contributing to Significant Tumor Accumulation of Albumin Nanoparticles |
title_short | Intravital Microscopy Reveals Endothelial Transcytosis Contributing to Significant Tumor Accumulation of Albumin Nanoparticles |
title_sort | intravital microscopy reveals endothelial transcytosis contributing to significant tumor accumulation of albumin nanoparticles |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9960641/ https://www.ncbi.nlm.nih.gov/pubmed/36839841 http://dx.doi.org/10.3390/pharmaceutics15020519 |
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