International journal of nanomedicine
A Multifunctional Metal-Based Nanomedicine for Copper Sequestration, in situ Toxification, and Immune Activation Against Metastatic Cancer
By Meng Y, Wang W, Guo W and 3 others.
Abstract
Objective
Tumor metastasis remains the principal cause of cancer-related mortality. However, current therapies often fail to effectively control both primary and disseminated lesions. Copper ions (Cu2⁺) are increasingly being recognized as key regulators of tumor progression, metastasis, and immune evasion. Leveraging their tumor-promoting properties as therapeutic targets is a promising anticancer strategy.
Methods
In this study, a multifunctional nanoplatform based on hyaluronic acid (HA)-stabilized and manganese-diethyldithiocarbamate (MnET) complex-loaded manganese dioxide (MnO2) nanosheets, denoted as MMH (MnET@MnO2-HA), was designed to deplete Cu2⁺ in the tumor microenvironment and simultaneously generate bioactive copper-diethyldithiocarbamate (CuET) in situ. MMH was systematically evaluated in terms of drug release, Cu2+ sequestration, in situ toxicity, and immune activation against primary and metastatic tumors, through both in vitro and in vivo experiments using animal models.