Redox-activatable inhalable mucoadhesive proteinic nanotherapeutics for targeted treatment of lung cancer

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials Pub Date : 2024-12-09 DOI:10.1016/j.biomaterials.2024.123004

Yeonsu Jeong , Yun Seop Shim , Yun Kee Jo , Hyung Joon Cha

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引用次数: 0

Abstract

Inhalation delivery has been considered a promising choice for treating lung cancer because it can shuttle therapeutic payloads directly to cancer tissues via simple and noninvasive procedures while reducing systemic toxicity. However, its clinical application still faces challenges, especially for delivering hydrophobic chemotherapeutic drugs, due to poor absorption on mucosal tissues and limited therapeutic performance. Herein, we propose inhalable mucoadhesive proteinic nanoparticles (NPs) capable of facilitating reliable pulmonary drug delivery and redox-responsive anticancer therapeutic effects to realize noninvasive, localized treatment of lung cancer in a highly biocompatible, site-specific manner. Thiolated mussel adhesive protein (MAP)-based NPs (thMAP NPs) can be administered to target tissues via an easy and facile nebulization process due to their superior MAP-driven adhesion ability and sufficient structural integrity. Curcumin (Cur)-loaded thMAP NPs (thMAP@Cur NPs) demonstrated efficient cellular uptake through the thiol-mediated pathway and controlled the intracellular release of Cur in response to the reductive environment in cancer cells. The nebulized thMAP@Cur NPs elicited prolonged retention in lung tissue without causing any detectable adverse effects, leading to significant inhibition of metastatic lung cancer in vivo. Thus, these protein-based redox-responsive mucoadhesive NPs hold great promise as robust inhalable drug delivery platforms to achieve effective, localized treatment of pulmonary cancer and other respiratory diseases.

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用于肺癌靶向治疗的可氧化还原激活可吸入黏附蛋白纳米疗法。

吸入给药被认为是治疗肺癌的一个很有前途的选择，因为它可以通过简单和无创的程序将治疗有效载荷直接输送到癌症组织，同时降低全身毒性。然而，由于其对粘膜组织的吸收较差，治疗效果有限，其临床应用仍面临挑战，特别是在递送疏水化疗药物方面。在此，我们提出了一种可吸入的黏附蛋白纳米颗粒（NPs），它能够促进可靠的肺部药物输送和氧化还原反应性抗癌治疗效果，以高度生物相容性和部位特异性的方式实现肺癌的无创、局部治疗。巯基贻贝粘附蛋白（MAP）为基础的NPs （thMAP NPs）由于其优越的MAP驱动的粘附能力和足够的结构完整性，可以通过简单易用的雾化过程给药到目标组织。姜黄素（Cur）负载的thMAP NPs （thMAP@Cur NPs）通过巯基介导的途径显示出有效的细胞摄取，并在癌细胞中响应还原环境控制细胞内Cur的释放。雾化的thMAP@Cur NPs在肺组织中引起长时间滞留，而不会引起任何可检测到的不良反应，导致体内转移性肺癌的显著抑制。因此，这些基于蛋白质的氧化还原反应黏附NPs作为强大的可吸入药物递送平台，有望实现肺癌和其他呼吸系统疾病的有效、局部治疗。

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

Biomaterials 工程技术-材料科学：生物材料

CiteScore

26.00

自引率

2.90%

发文量

565

审稿时长

46 days

期刊介绍： Biomaterials is an international journal covering the science and clinical application of biomaterials. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. It is the aim of the journal to provide a peer-reviewed forum for the publication of original papers and authoritative review and opinion papers dealing with the most important issues facing the use of biomaterials in clinical practice. The scope of the journal covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. These sciences include polymer synthesis and characterization, drug and gene vector design, the biology of the host response, immunology and toxicology and self assembly at the nanoscale. Clinical applications include the therapies of medical technology and regenerative medicine in all clinical disciplines, and diagnostic systems that reply on innovative contrast and sensing agents. The journal is relevant to areas such as cancer diagnosis and therapy, implantable devices, drug delivery systems, gene vectors, bionanotechnology and tissue engineering.