Enhanced anti-metastatic therapy with down-regulation of heparinase expression by ROS-responsive micellar nanoparticles. Issue 36 (3rd September 2021)

• Record Type: Journal Article
• Authors: Zhang, Yicong; Li, Yuai; Huang, Shiqi; Zhang, Hanming; Lin, Qing; Gong, Tao; Sun, Xun; Zhang, Zhirong; Zhang, Ling
• Is Part Of: Nanoscale. Volume 13:Issue 36(2021)
• Page Start: 15267
• Page End: 15277
• Publication Date: 2021-09-03
• Subjects: Nanoscience -- Periodicals; Nanotechnology -- Periodicals; 620.505
• DOI: 10.1039/d1nr02964a
• Languages: English
• ISSNs: 2040-3364

Abstract

Abstract : Schematic illustration of DOX-nPLPs targeting a melanoma solid tumor and inhibiting lung metastasis. Abstract : Metastasis is a major sign of malignant tumors which plays a vital role in cancer-related death. Suppressing metastasis is an important way to improve the survival rate of cancer patients. Herein, multifunctional PEG–LAM–PPS nanoparticles (nPLPs) are fabricated as both nanocarriers and anti-metastatic agents for tumor treatment. In this system, laminarin sulfate (LAM) suppresses metastasis by reducing heparinase and protecting the extracellular matrix; the ROS-sensitive polypropylene sulfide (PPS) improves the release of the loaded drug in the tumor microenvironment. This is the first time that laminarin sulfate has been used as a carrier to inhibit the expression of heparinase and treat melanoma lung metastasis. The blank nanoparticles are excellently safe and showed high anti-metastatic efficacy in melanoma lung metastatic mouse models, reducing metastatic nodules by 60%. They significantly improved the anti-tumor efficacy of the loaded drug doxorubicin, provided ∼33% further reduction of the tumor volume and 50% further reduction of the metastatic nodule number compared with free doxorubicin. Thus, these simple and versatile micellar nanoparticles composed of biocompatible materials offer a promising vehicle for treating invasive solid tumors and metastases.