Hierarchically Released Liquid Metal Nanoparticles for Mild Photothermal Therapy/Chemotherapy of Breast Cancer Bone Metastases via Remodeling Tumor Stromal Microenvironment,Advanced Healthcare Materials

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Hierarchically Released Liquid Metal Nanoparticles for Mild Photothermal Therapy/Chemotherapy of Breast Cancer Bone Metastases via Remodeling Tumor Stromal Microenvironment
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2023-07-12 , DOI: 10.1002/adhm.202301080
Yaping Shen ₁ , Yang Zou ₂ , Binglin Bie ₃ , Yonggang Lv ₃

Affiliation

Currently, the treatment strategy for bone metastasis is mainly to inhibit the growth of tumor cells and the activity of osteoclasts, while ignoring the influence of the tumor stromal microenvironment (TSM) on the progression of bone metastasis. Herein, a dual-target liquid metal (LM)-based drug delivery system (DDS) with favorable photothermal performance is designed to spatially program the delivery of multiple therapeutic agents to enhance the treatment of bone metastasis through TSM remodeling. Briefly, mesoporous silicon-coated LM is integrated into zeolitic imidazolate framework-8 (ZIF-8) with both bone-seeking and tumor-targeting capacities. Curcumin (Cur), a tumor microenvironment modulator, is encapsulated into ZIF-8, and doxorubicin (DOX) is enclosed inside mesoporous silicon. Specific accumulation of the LM-based DDS in bone metastases first relieves the tumor stroma by releasing Cur in response to the acidic tumor microenvironment and then releases DOX deep into the tumor under near-infrared light irradiation. The combined strategy of the LM-based DDS and mild photothermal therapy has been shown to effectively restrain cross-talk between osteoclasts and tumor cells by inhibiting the secretion of transforming growth factor-β, degrading extracellular matrix components, and increasing infiltration of CD4⁺ and CD8⁺ T cells, which provides a promising strategy for the treatment of bone metastases.

中文翻译：

分层释放的液态金属纳米粒子通过重塑肿瘤基质微环境用于乳腺癌骨转移的温和光热治疗/化疗

目前骨转移的治疗策略主要是抑制肿瘤细胞的生长和破骨细胞的活性，而忽视了肿瘤基质微环境（TSM）对骨转移进展的影响。在此，设计了一种具有良好光热性能的双靶点液态金属（LM）药物递送系统（DDS），可对多种治疗药物的递送进行空间编程，通过TSM重塑增强骨转移的治疗。简而言之，介孔硅涂层LM被集成到沸石咪唑酯骨架-8（ZIF-8）中，具有骨寻找和肿瘤靶向能力。肿瘤微环境调节剂姜黄素 (Cur) 被封装在 ZIF-8 中，阿霉素 (DOX) 被封装在介孔硅内。基于LM的DDS在骨转移中的特异性积累首先通过响应酸性肿瘤微环境释放Cur来缓解肿瘤基质，然后在近红外光照射下将DOX释放到肿瘤深处。^{基于LM的DDS和温和光热疗法的联合策略已被证明可以通过抑制转化生长因子-β的分泌、降解细胞外基质成分以及增加CD4 +}和CD4+和肿瘤细胞的浸润来有效抑制破骨细胞和肿瘤细胞之间的串扰。CD8 ⁺ T细胞，这为骨转移的治疗提供了一种有前景的策略。

更新日期：2023-07-12

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