The current research on tumor fibrosis mainly focuses on cancer associated fibroblasts, which may play a dual role in promoting and inhibiting tumors. However, whether tumor cells themselves can undergo fibrosis transformation and inhibit parenchymal cells like pulmonary fibrosis to achieve the goal of inhibiting malignant progression of tumors has received less attention.
On August 29, 2024, Advanced Science reported that researchers used mesoporous silica nanoparticles (MSN) loaded with trehalose mycorrhizal ester (TDM) to induce tumor cell fibrosis through the dual effects of TDM induced inflammatory granulomas and MSN induced foreign body granulomas.

In this work, researchers prepared novel nanoparticles loaded with MSN and TDM, and utilized the dual induction of fibrosis by MSN and TDM to construct a mouse subcutaneous loaded tumor model. They observed its anti-tumor effect and the possibility of inhibiting tumor malignant progression by inducing tumor cell fibroblast transformation, in order to develop a new anti-tumor strategy.
Combining in vitro and in vivo studies, it has been shown that TDM/MSN (TM) can effectively enter solid tumors and induce tumor fibrosis, manifested by collagen internalization and inhibition of proliferation and invasion ability, suggesting a potential role in the treatment of tumor fibrosis.
But further research has found that extracellular DNA (ecDNA) mediates resistance to fibrosis induction. In order to comprehensively improve the therapeutic effect, WRN nuclease binds with TM to form a novel nanoparticle (TMW), which can effectively clear ecDNA and promote fibroblast like transformation of tumor cells. Its inhibitory effect on cancer progression has been verified in the PDX model.

This study reveals the potential of TDM/MSN-WRN (TMW) to induce fibroblast like transformation and related intracellular collagen deposition in tumor cells, thereby inhibiting malignant progression of tumors. It provides a new paradigm for anti-tumor therapy and offers a new theoretical basis and strategy for designing anti-tumor drugs.

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