Macrophage membrane-derived pH-responsive nanovesicles to target tumor cells with integrin α4β1 receptor

IF 2.8 4区工程技术 Q2 POLYMER SCIENCE

Macromolecular Research Pub Date : 2023-12-19 DOI:10.1007/s13233-023-00226-6

Jaehyun Kang, Eunsol Lee, Eun Seong Lee

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Abstract

In this study, we developed macrophage-derived nanovesicles (MNVs) to specifically target tumor cells. Initially, we chemically coupled hyaluronic acid (HA) with 3-(diethylamino)propylamine (DEAP; with a pK_b value of approximately 7.0) to confer pH-responsive properties. The resulting polymer (HDEA) and chlorin e6 (Ce6, serving as a photosensitizing model drug) were incorporated into MNVs using a sonication process, resulting in Ce6-loaded HDEA@MNVs. Our experiments demonstrated that the integrin α4β1 expressed in MNVs selectively interacted with vascular cell adhesion molecule-1 (VCAM-1) in SK-N-MC tumor cells, leading to enhanced accumulation of MNVs within the tumor cells. Consequently, HDEA@MNVs exhibited significant accumulation within tumor cells, underwent structural destabilization at endosomal pH due to the protonation of pH-responsive DEAP within the HDEA@MNVs, and facilitated the release of Ce6. The released free Ce6 from MNVs exhibited improved effectiveness in photodynamic tumor therapy when exposed to laser irradiation. In vitro cell experiments demonstrated efficient internalization of HDEA@MNVs into tumor cells and high efficacy in photodynamic therapy.

Graphical abstract

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利用整合素 α4β1 受体靶向肿瘤细胞的巨噬细胞膜源性 pH 响应纳米颗粒

摘要在这项研究中，我们开发了巨噬细胞衍生纳米囊泡 (MNVs)，用于特异性靶向肿瘤细胞。首先，我们将透明质酸（HA）与3-(二乙氨基)丙胺（DEAP，pKb值约为7.0）进行化学偶联，以赋予其pH响应特性。通过超声处理将得到的聚合物（HDEA）和作为光敏模型药物的氯素 e6（Ce6）加入到 MNV 中，得到了负载 Ce6 的 HDEA@MNV。我们的实验证明，MNVs 中表达的整合素 α4β1 能选择性地与 SK-N-MC 肿瘤细胞中的血管细胞粘附分子-1（VCAM-1）相互作用，从而增强 MNVs 在肿瘤细胞内的聚集。因此，HDEA@MNVs 在肿瘤细胞内显著积累，由于 HDEA@MNVs 内 pH 响应型 DEAP 的质子化作用，在内质体 pH 下发生结构失稳，并促进 Ce6 的释放。在激光照射下，从 MNVs 中释放的游离 Ce6 在光动力肿瘤治疗中表现出更好的效果。体外细胞实验表明，HDEA@MNVs能有效内化到肿瘤细胞中，在光动力治疗中具有很高的疗效。图表摘要

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来源期刊

Macromolecular Research 工程技术-高分子科学

CiteScore

4.70

自引率

8.30%

发文量

100

审稿时长

1.3 months

期刊介绍： Original research on all aspects of polymer science, engineering and technology, including nanotechnology Presents original research articles on all aspects of polymer science, engineering and technology Coverage extends to such topics as nanotechnology, biotechnology and information technology The English-language journal of the Polymer Society of Korea Macromolecular Research is a scientific journal published monthly by the Polymer Society of Korea. Macromolecular Research publishes original researches on all aspects of polymer science, engineering, and technology as well as new emerging technologies using polymeric materials including nanotechnology, biotechnology, and information technology in forms of Articles, Communications, Notes, Reviews, and Feature articles.