Lipid Nanoparticle Delivery System for Normalization of Tumor Microenvironment and Tumor Vascular Structure.

IF 8.1 Q1 ENGINEERING, BIOMEDICAL

Biomaterials research Pub Date : 2025-02-11 eCollection Date: 2025-01-01 DOI:10.34133/bmr.0144

Heejin Ha, Yonghyun Choi, Na-Hyeon Kim, Jiwon Kim, Jaehee Jang, Tagbo H R Niepa, Masayoshi Tanaka, Hee-Young Lee, Jonghoon Choi

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Abstract

Tumors grow by receiving oxygen and nutrients from the surrounding blood vessels, leading to rapid angiogenesis. This results in functionally and structurally abnormal vasculature characterized by high permeability and irregular blood flow, causing hypoxia within the tumor microenvironment (TME). Hypoxia exacerbates the secretion of pro-angiogenic factors such as vascular endothelial growth factor (VEGF), further perpetuating abnormal vessel formation. This environment compromises the efficacy of radiotherapy, immunotherapy, and chemotherapy. In this study, we developed a pH-sensitive liposome (PSL) system, termed OD_PSL@AKB, to co-deliver oxygen (OD) and razuprotafib (AKB-9778) to tumors. This system rapidly responds to the acidic TME to alleviate hypoxia and inhibit VEGF secretion, restoring VE-cadherin expression in hypoxic endothelial cell/cancer cell cocultures. Our findings highlight the potential of OD_PSL@AKB in normalizing tumor vasculature and improving therapeutic efficacy.

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脂质纳米颗粒输送系统用于肿瘤微环境和肿瘤血管结构的正常化。

肿瘤通过接受周围血管的氧气和营养物质生长，导致血管快速生成。这导致功能和结构上的血管异常，其特征是高通透性和不规则血流，导致肿瘤微环境（TME）内缺氧。缺氧加剧了促血管生成因子如血管内皮生长因子（VEGF）的分泌，进一步延续了异常血管的形成。这种环境影响了放疗、免疫治疗和化疗的疗效。在这项研究中，我们开发了一种ph敏感脂质（PSL）系统，称为OD_PSL@AKB，用于将氧（OD）和razuprotafib （AKB-9778）共同递送到肿瘤。该系统快速响应酸性TME，缓解缺氧，抑制VEGF分泌，恢复缺氧内皮细胞/癌细胞共培养VE-cadherin的表达。我们的研究结果强调OD_PSL@AKB在肿瘤血管正常化和提高治疗效果方面的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Biomaterials research

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