Iterative Design of a Prodrug Nanocarrier for Cell Cycle Arrest, Immune Modulation, and Enhanced T Cell Infiltration for Colon Cancer Therapy

IF 9.6 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Letters Pub Date : 2025-02-10 DOI:10.1021/acs.nanolett.4c06018

Zhenhan Feng, Mengmeng Qin, Jinhong Jiang, Meng Wang, Tianyu Zhang, Yibo Li, Xiangsheng Liu, Jinfang Zhang, Hubing Shi, Yuliang Zhao, Huan Meng

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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 antitumor immunity. In this work, we iteratively designed prodrug liposomal nanocarriers that integrate multiple functions: cell cycle inhibition through encapsulation of CDK4/6i, immune activation via concurrent delivery of an oral gavage-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 antitumor efficacy, and synergizes with immune checkpoint inhibitors to provide lasting effects in various colon cancer animal models.

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来源期刊

Nano Letters 工程技术-材料科学：综合

CiteScore

16.80

自引率

2.80%

发文量

1182

审稿时长

1.4 months

期刊介绍： Nano Letters serves as a dynamic platform for promptly disseminating original results in fundamental, applied, and emerging research across all facets of nanoscience and nanotechnology. A pivotal criterion for inclusion within Nano Letters is the convergence of at least two different areas or disciplines, ensuring a rich interdisciplinary scope. The journal is dedicated to fostering exploration in diverse areas, including: - Experimental and theoretical findings on physical, chemical, and biological phenomena at the nanoscale - Synthesis, characterization, and processing of organic, inorganic, polymer, and hybrid nanomaterials through physical, chemical, and biological methodologies - Modeling and simulation of synthetic, assembly, and interaction processes - Realization of integrated nanostructures and nano-engineered devices exhibiting advanced performance - Applications of nanoscale materials in living and environmental systems Nano Letters is committed to advancing and showcasing groundbreaking research that intersects various domains, fostering innovation and collaboration in the ever-evolving field of nanoscience and nanotechnology.