A Self‐Assembling LYTAC Mediates CTGF Degradation and Remodels Inflammatory Tumor Microenvironment for Triple‐Negative Breast Cancer Therapy DOI Creative Commons
Jiayi Lin, Ye Wu, Xiao‐Hui Liang

и другие.

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Май 11, 2025

Abstract As a multifunctional extracellular protein, connective tissue growth factor (CTGF/CCN2) is significantly associated with the progression and prognosis of triple‐negative breast cancer (TNBC). However, current blockade therapies targeting CTGF's multiple domains are limited, creating substantial challenges in treatment. Lysosome‐targeting chimeras (LYTACs) have emerged as promising approach for achieving complete protein degradation inhibiting various bioactivities. In this study, self‐assembling LYTAC nanoplatform, NanoCLY, designed to tumor microenvironment (TME)‐responsively degrade CTGF presented. The downregulates TGF‐β signaling pathway disrupts CTGF‐IL‐6 cell crosstalk within TME, which further inhibits activation inflammatory cancer‐associated fibroblasts (CAFs) alleviates TME. Notably, anti‐TNBC effect LYTAC‐based therapy surpasses that antibody‐based both vitro vivo models. findings provide proof concept TNBC introduce first CTGF‐LYTAC nanoplatform aimed at TME‐directed therapy.

Язык: Английский

A Self‐Assembling LYTAC Mediates CTGF Degradation and Remodels Inflammatory Tumor Microenvironment for Triple‐Negative Breast Cancer Therapy DOI Creative Commons
Jiayi Lin, Ye Wu, Xiao‐Hui Liang

и другие.

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Май 11, 2025

Abstract As a multifunctional extracellular protein, connective tissue growth factor (CTGF/CCN2) is significantly associated with the progression and prognosis of triple‐negative breast cancer (TNBC). However, current blockade therapies targeting CTGF's multiple domains are limited, creating substantial challenges in treatment. Lysosome‐targeting chimeras (LYTACs) have emerged as promising approach for achieving complete protein degradation inhibiting various bioactivities. In this study, self‐assembling LYTAC nanoplatform, NanoCLY, designed to tumor microenvironment (TME)‐responsively degrade CTGF presented. The downregulates TGF‐β signaling pathway disrupts CTGF‐IL‐6 cell crosstalk within TME, which further inhibits activation inflammatory cancer‐associated fibroblasts (CAFs) alleviates TME. Notably, anti‐TNBC effect LYTAC‐based therapy surpasses that antibody‐based both vitro vivo models. findings provide proof concept TNBC introduce first CTGF‐LYTAC nanoplatform aimed at TME‐directed therapy.

Язык: Английский

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