Iteratively Designed Nanocarrier for Cell Cycle Arrest, Immune Boost, and T Cell Access
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Recent advancements in cancer therapy have highlighted the dual role of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in both cell cycle regulation and immune activation. However, applying CDK4/6i to immunologically unfavorable tumors is challenging due to the complex tumor microenvironment (TME), characterized by inadequate T cell recruitment and exclusion mechanisms that hinder an effective anti-tumor immunity. Here, we iteratively designed prodrug liposomal nanocarriers that integrate multiple functions: cell cycle inhibition through CDK4/6i encapsulation, immune activation via concurrent delivery of an immunogenic cell death-inducing chemotherapy agent, and overcoming T cell exclusion through the incorporation of a cholesterol prodrug. This iterative nanocarrier design effectively improves the pharmacokinetic profile of CDK4/6i, overcomes the immunosuppressive TME, achieves superior anti-tumor efficacy, and synergizes with immune checkpoint inhibitors to provide lasting effects in various colon cancer animal models.