Manganese mineralization based stromal depleter priming nanomedicine penetration for robust cancer therapy

作者：Yunyang Zhang, Siying Chen, Yuxin Wang, Jingjing Zhang, Xinyan Yang, Haoran Li, Hong-Xia Dai, Shibo Wang, M. Zubair Iqbal, Yao Li, Xiangdong Kong, Ruibo Zhao · 发表于：Nano Research · 年份：2025 · DOI：10.26599/nr.2025.94908058 · 被引用次数：4 · 研究领域：Nanoparticle-Based Drug Delivery、Graphene and Nanomaterials Applications、Cancer Research and Treatments

Poor tumor penetration is a significant challenge for using nanoliposome-based chemotherapy for triple-negative breast cancer (TNBC). Recently, a milieu of biological cues downregulating tumor stroma has been associated with biological metal ions, primarily such as Mn 2+ . Inspired by this, we hypothesized that Mn 2+ could serve as a functional component in designing an alternative modulator for the tumor stroma microenvironment by reducing its extracellular matrix, further decreasing its stromal density. Herein, we presented a novel extracellular matrix (ECM) depleter within a tumor involving manganese-based mineralization materials that primed inhibition of the extracellular matrix of cancer cells, demonstrating a facile strategy for improving drug penetration, delivery and therapy efficiency of DOX-loaded liposomes (Dox-LNP). As a result, the manganese mimetic mineralization material, manganese phosphate (MnP), demonstrated controlled biodegradation and biocompatibility within tumor microenvironments. The release of Mn 2+ from MnP within the cell lysosome or tumor microenvironment inhibited TGF-β expression and its downstream profibrotic signaling pathways, thereby reducing the tumor stroma density by suppressing the expression of α-smooth actin (α-SMA) and collagen I (COL-I), and inducing tumor stromal disruption both in vitro and in vivo . The typical nanomedicines, Dox-LNP, were subsequently used to check their penetration. The MnP pretreated tumor could significan...