An alternative way to break the matrix barrier: an experimental study of a LIFU-mediated, visualizable targeted nanoparticle synergistic amplification for the treatment of malignant fibroblasts.

IF 4.3 3区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Frontiers in Bioengineering and Biotechnology Pub Date : 2024-11-05 eCollection Date: 2024-01-01 DOI:10.3389/fbioe.2024.1486369

Xiangzhi Zhao, Zhengchao Fan, Junan Zhou, Ying Li, Weiwei Zhu, Song Su, Jizhu Xia

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Abstract

Malignant fibroblasts (MFs) are widely present in various diseases and are characterized by connective tissue proliferation; these cells act as a physical barrier that severely limits drug delivery and affects disease outcomes. Based on this, we constructed the smart, integrated, theranostic, targeted lipid nanoprobe HMME-RG3@PFH to overcome the bottleneck in the early diagnosis and treatment of MF-related diseases. The protein glucose transporter protein 1 (GLUT-1) is overexpressed on MFs, and its ideal substrate, ginsenoside RG3 (RG3), significantly enhances the targeted uptake of HMME-RG3@PFH by MFs in a hypoxic environment and endows the nanomaterial with stealthiness to prolong its circulation. Perfluorohexane (PFH), a substance that can undergo phase change, was encapsulated in the lipid core and vaporized for ultrasound-enhanced imaging under low-intensity focused ultrasound (LIFU) irradiation. Moreover, hematoporphyrin monomethyl ether (HMME) was loaded into the lipid bilayer for photoacoustic molecular imaging and sonodynamic therapy (SDT) of MFs under the combined effects of LIFU. Additionally, HMME-RG3@PFH instantaneously burst during visualization to promote targeted drug delivery. In addition, the increased number of exposed RG3 fragments can regulate the MFs to enter a quiescent state. Overall, this nanoplatform ultimately achieves dual-modal imaging with targeted and precise drug release for visualization and synergistic amplification therapy, providing a new possibility for the early diagnosis and precise treatment of MF-related diseases.

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打破基质屏障的另一种方法：对 LIFU 介导的可视化靶向纳米粒子协同放大治疗恶性成纤维细胞的实验研究。

恶性成纤维细胞（MFs）广泛存在于各种疾病中，其特点是结缔组织增生；这些细胞作为一种物理屏障，严重限制了药物的输送并影响疾病的治疗效果。基于此，我们构建了智能、集成、治疗、靶向脂质纳米探针 HMME-RG3@PFH，以突破 MF 相关疾病早期诊断和治疗的瓶颈。葡萄糖转运蛋白1（GLUT-1）在中耳炎患者身上过度表达，而其理想底物人参皂苷RG3（RG3）能显著提高中耳炎患者在缺氧环境中对HMME-RG3@PFH的靶向吸收，并赋予纳米材料隐身性，延长其循环时间。全氟己烷（PFH）是一种能发生相变的物质，它被包裹在脂质核心中，并在低强度聚焦超声（LIFU）照射下气化，用于超声增强成像。此外，还将血卟啉单甲醚（HMME）载入脂质双分子层，在低强度聚焦超声（LIFU）的联合作用下对中耳炎进行光声分子成像和声动力治疗（SDT）。此外，HMME-RG3@PFH 在可视化过程中瞬时迸发，促进了药物的靶向输送。此外，暴露的 RG3 片段数量的增加还能调节中耳炎进入静息状态。总之，这种纳米平台最终实现了双模式成像，既能靶向精确释放药物进行显像，又能协同放大治疗，为中频相关疾病的早期诊断和精确治疗提供了新的可能。

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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来源期刊

Frontiers in Bioengineering and Biotechnology Chemical Engineering-Bioengineering

CiteScore

8.30

自引率

5.30%

发文量

2270

审稿时长

12 weeks

期刊介绍： The translation of new discoveries in medicine to clinical routine has never been easy. During the second half of the last century, thanks to the progress in chemistry, biochemistry and pharmacology, we have seen the development and the application of a large number of drugs and devices aimed at the treatment of symptoms, blocking unwanted pathways and, in the case of infectious diseases, fighting the micro-organisms responsible. However, we are facing, today, a dramatic change in the therapeutic approach to pathologies and diseases. Indeed, the challenge of the present and the next decade is to fully restore the physiological status of the diseased organism and to completely regenerate tissue and organs when they are so seriously affected that treatments cannot be limited to the repression of symptoms or to the repair of damage. This is being made possible thanks to the major developments made in basic cell and molecular biology, including stem cell science, growth factor delivery, gene isolation and transfection, the advances in bioengineering and nanotechnology, including development of new biomaterials, biofabrication technologies and use of bioreactors, and the big improvements in diagnostic tools and imaging of cells, tissues and organs. In today`s world, an enhancement of communication between multidisciplinary experts, together with the promotion of joint projects and close collaborations among scientists, engineers, industry people, regulatory agencies and physicians are absolute requirements for the success of any attempt to develop and clinically apply a new biological therapy or an innovative device involving the collective use of biomaterials, cells and/or bioactive molecules. “Frontiers in Bioengineering and Biotechnology” aspires to be a forum for all people involved in the process by bridging the gap too often existing between a discovery in the basic sciences and its clinical application.