Regulating lactate-related immunometabolism and EMT reversal for colorectal cancer liver metastases using shikonin targeted delivery.

ABSTRACT:

Background

There are few effective medications for treating colorectal cancer and liver metastases (CRLM). The interactions among glycolysis, epithelial-mesenchymal transition (EMT), and immune microenvironment contribute to the progression of CRLM. A main glycolytic enzyme pyruvate Kinase M2 (PKM2) is highly expressed in colorectal cancer and CRLM, and thus can be a potential therapeutic target.

Methods

A therapeutic strategy was proposed and the shikonin-loaded and hyaluronic acid-modified MPDA nanoparticles (SHK@HA-MPDA) were designed for CRLM therapy via PKM2 inhibition for immunometabolic reprogramming. The treatment efficacy was evaluated in various murine models with liver metastasis of colorectal tumor.

Results

SHK@HA-MPDA achieved tumor-targeted delivery via

SUBMITTER: Long L 

PROVIDER: S-EPMC10170793 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature