机构：[1]CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China.[2]University of Chinese Academy of Sciences, Beijing 100049, China.[3]Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China.浙江省肿瘤医院[4]Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China.[5]Department of Hepatobiliary and Pancreatic Surgery, Medical Research Institute, Frontier Science Center of Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.[6]Institute of Breast Health Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, Sichuan 610041, China.四川大学华西医院[7]College of Chemistry and Materials Science, Jinan University, Guangzhou 510632, China.
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.
基金：
This work was supported by the National Key Research and
Development Program of China (2022YFA1207300 and
2021YFA1200902), the National Natural Science Foundation
of China (82204300, 32271452, and 32201143), the Basic
Science Center Project of the National Natural Science
Foundation of China (22388101), and the CAS Project for
Young Scientists in Basic Research (Grant YSBR-036).
第一作者机构：[1]CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China.[2]University of Chinese Academy of Sciences, Beijing 100049, China.
通讯作者：
通讯机构：[1]CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China.[2]University of Chinese Academy of Sciences, Beijing 100049, China.[7]College of Chemistry and Materials Science, Jinan University, Guangzhou 510632, China.
推荐引用方式(GB/T 7714)：
Feng Zhenhan,Qin Mengmeng,Jiang Jinhong,et al.Iterative Design of a Prodrug Nanocarrier for Cell Cycle Arrest, Immune Modulation, and Enhanced T Cell Infiltration for Colon Cancer Therapy[J].Nano Letters.2025,25(7):2820-2830.doi:10.1021/acs.nanolett.4c06018.
APA：
Feng Zhenhan,Qin Mengmeng,Jiang Jinhong,Wang Meng,Zhang Tianyu...&Meng Huan.(2025).Iterative Design of a Prodrug Nanocarrier for Cell Cycle Arrest, Immune Modulation, and Enhanced T Cell Infiltration for Colon Cancer Therapy.Nano Letters,25,(7)
MLA：
Feng Zhenhan,et al."Iterative Design of a Prodrug Nanocarrier for Cell Cycle Arrest, Immune Modulation, and Enhanced T Cell Infiltration for Colon Cancer Therapy".Nano Letters 25..7(2025):2820-2830
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