Gold nanoparticles enhance cisplatin delivery and potentiate chemotherapy by decompressing colorectal cancer vessels

Abstract

Xiaoxu Zhao,1,* Jinghua Pan,1,* Wei Li,1 Wende Yang,1 Li Qin,2 Yunlong Pan1 1Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China; 2Department of Histology and Embryology, Medical School of Jinan University, Guangzhou 510632, China *These authors contributed equally to this work 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: gold nanoparticles, colorectal cancer, vessel, decompression, solid stress, hypoxia 

Keywords

• gold nanoparticles
• colorectal cancer
• vessel
• decompression
• solid stress
• hypoxia