Gold nanoparticles enhance cisplatin delivery and potentiate chemotherapy by decompressing colorectal cancer vessels
Open Access
- 1 October 2018
- journal article
- research article
- Published by Informa UK Limited in International Journal of Nanomedicine
- Vol. ume 13, 6207-6221
- https://doi.org/10.2147/ijn.s176928
Abstract
Background: Tumor vessels were persistently compressed by solid stress from tumor interstitial matrix, resulting in limited vessel perfusion and oxygen concentrations. Collagen within matrix participated in transmitting the solid stress to tumor vessels and limiting drug delivery. Purpose: The objective of this study was to identify whether gold nanoparticles (AuNPs) were able to decompress colorectal cancer vessels and enhance vessel perfusion as well as drug delivery in colorectal cancer. Methods: Colorectal cancer xenograft mice were treated with AuNPs or normal saline for 14 days. The cancer stromal collagen I level, cancer vessel perfusion, hypoxia of tumor were tested by histological examination. We also test the solid stress in the two groups. Furtherly, the effect and the drug delivery of combined using AuNPs and cisplatin were tested. The effect and the underlying mechanism of AuNPs on SW620 cells were tested by CCK8, flow cytometry, Western-blot and atomic force microscope. Results: AuNPs were able to decrease the density of colorectal cancer associated fibroblasts (CAFs), to reduce the production of tumor stromal collagen I, and to diminish the expression of profibrotic signals, including CTGF, TGF-β1 as well as VEGF in vivo and vitro via Akt signaling pathway. Consequently, AuNPs could alleviate solid stress in tumors, subsequently leading to enhanced vessel perfusion. Therefore, cisplatin as well as oxygen delivery to tumors were improved by AuNPs, which reduced hypoxia while sensitizing therapy of cisplatin in colorectal cancer model. Conclusion: AuNPs were effective agents in enhancing cisplatin delivery and potentiating inhibiting tumor growth by decompressing colorectal cancer vessels.Keywords
This publication has 49 references indexed in Scilit:
- Causes, consequences, and remedies for growth-induced solid stress in murine and human tumorsProceedings of the National Academy of Sciences of the United States of America, 2012
- The extracellular matrix: A dynamic niche in cancer progressionThe Journal of cell biology, 2012
- Increased Survival of Glioblastoma Patients Who Respond to Antiangiogenic Therapy with Elevated Blood PerfusionCancer Research, 2012
- Mechanism of anti-angiogenic property of gold nanoparticles: role of nanoparticle size and surface chargeNanomedicine: Nanotechnology, Biology and Medicine, 2011
- Biomechanical Remodeling of the Microenvironment by Stromal Caveolin-1 Favors Tumor Invasion and MetastasisCell, 2011
- Aligned Collagen Is a Prognostic Signature for Survival in Human Breast CarcinomaThe American Journal of Pathology, 2011
- Visfatin induces human endothelial VEGF and MMP-2/9 production via MAPK and PI3K/Akt signalling pathways: novel insights into visfatin-induced angiogenesisCardiovascular Research, 2007
- Mammographic Density and the Risk and Detection of Breast CancerNew England Journal of Medicine, 2007
- Fibroblasts in cancerNature Reviews Cancer, 2006
- VEGF induces proliferation, migration, and TGF-β1 expression in mouse glomerular endothelial cells via mitogen-activated protein kinase and phosphatidylinositol 3-kinaseBiochemical and Biophysical Research Communications, 2005