Issue 9, 2023

Cancer-associated fibroblast-targeted nanodrugs reshape colorectal tumor microenvironments to suppress tumor proliferation, metastasis and improve drug penetration

Abstract

Cancer-associated fibroblasts (CAFs) produce a critical tumor-promoting effect by cellular crosstalk with cancer cells and remodel the extracellular matrix (ECM) to form a protective physical barrier. The simple elimination of CAFs is not sufficient to govern the CAF-shaped aggressive tumor microenvironment (TME) because of the complexity of tumors. Herein, a CAF-targeted poly (lactic-co-glycolic acid) (PLGA) nanoemulsion is tailored to simultaneously deliver doxorubicin (DOX) and small interfering RNA (siRNA) targeting hepatocyte growth factor (HGF) for the combination of chemotherapy and gene therapy. The nanoemulsion (apt-Si/DNPs) shows a high specificity towards CAFs due to the aptamer modification and efficiently induces the apoptosis of CAFs, thus decreasing ECM deposition in the TME. Importantly, the delivered siRNA reduces the expression of the HGF in the remaining CAFs, which overcomes chemotherapy-induced upregulation of HGF mRNA and prevents the reproduction of CAFs through the autocrine HGF closed-loop. Owing to these synergetic effects, tumor proliferation, migration and invasion are prominently inhibited and tumor permeability is improved significantly. Overall, these results emphasize the potential of CAF-targeted combination treatments to inhibit tumor progression and metastasis, as well as overcome therapeutic resistance.

Graphical abstract: Cancer-associated fibroblast-targeted nanodrugs reshape colorectal tumor microenvironments to suppress tumor proliferation, metastasis and improve drug penetration

Supplementary files

Article information

Article type
Paper
Submitted
18 Okt. 2022
Accepted
19 Nov. 2022
First published
22 Nov. 2022

J. Mater. Chem. B, 2023,11, 1871-1880

Cancer-associated fibroblast-targeted nanodrugs reshape colorectal tumor microenvironments to suppress tumor proliferation, metastasis and improve drug penetration

W. Shen, P. Yao, W. Li, C. Gu, T. Gao, Y. Cao, Z. Wang, R. Pei and C. Xing, J. Mater. Chem. B, 2023, 11, 1871 DOI: 10.1039/D2TB02253B

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements