Tumor-targeted nanosystem with hypoxia inducible factor 1α inhibition for synergistic chemo-photodynamic therapy against hypoxic tumor

IF 5.4 2区医学 Q1 BIOPHYSICS

Colloids and Surfaces B: Biointerfaces Pub Date : 2024-12-12 DOI:10.1016/j.colsurfb.2024.114456

Ruifeng Zeng , Rui Zhou , Lu Zhen , Jinshuai Lan , Zhe Li , Donghao Gu , Wenlong Nie , Yi Shen , Minquan Zhang , Tong Zhang , Yue Ding

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引用次数: 0

Abstract

Photodynamic therapy (PDT) holds an essential role in the therapy of tumors. However, PDT consumes tissue oxygen and diminishes its own efficacy by inducing tumor hypoxia through the HIF-1α/VEGF pathway. Therefore, overcoming the photodynamic exacerbation of tumor hypoxia could reverse tumor microenvironment and enhance PDT. In this study, BC-PDA/HA loaded with bufalin (BUF) and chlorin e6 (Ce6) were developed for synergistic cancer chemo-photodynamic therapy. BC-PDA/HA, modified with hyaluronic acid (HA), exhibited CD44-targeting capability and enhanced cellular uptake in vitro. Moreover, in the acidic tumor microenvironment, BC-PDA/HA could on-demand release Ce6 and BUF, inducing PDT upon 660 nm irradiation. Simultaneously, the released BUF not only served as a chemotherapeutic agent, but also inhibited HIF-1α expression, reversing the PDT-induced tumor hypoxia. Furthermore, compared to free Ce6, BC-PDA/HA enhanced tumor accumulation and retention in vivo. BC-PDA/HA could also effectively improve hypoxia and inhibit tumor angiogenesis to enhance PDT efficacy, demonstrating synergistic chemo-PDT activity. In conclusion, this work provided a novel strategy for synergistic chemo-photodynamic therapy against breast cancer.

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具有缺氧诱导因子1α抑制的肿瘤靶向纳米系统对缺氧肿瘤的协同化学光动力治疗。

光动力疗法（PDT）在肿瘤治疗中起着至关重要的作用。然而，PDT通过HIF-1α/VEGF途径诱导肿瘤缺氧，消耗组织氧，降低自身疗效。因此，克服肿瘤缺氧的光动力恶化可以逆转肿瘤微环境，增强PDT。在这项研究中，BC-PDA/HA负载蟾毒灵（BUF）和氯e6 （Ce6）用于协同癌症化学光动力治疗。BC-PDA/HA经透明质酸修饰后，表现出靶向cd44的能力，并增强了体外细胞摄取。在酸性肿瘤微环境下，BC-PDA/HA可按需释放Ce6和BUF，在660 nm照射下诱导PDT。同时，释放的BUF不仅可以作为化疗药物，还可以抑制HIF-1α的表达，逆转pdt诱导的肿瘤缺氧。此外，与游离Ce6相比，BC-PDA/HA增强了肿瘤在体内的积累和滞留。BC-PDA/HA还能有效改善缺氧，抑制肿瘤血管生成，增强PDT疗效，具有协同化疗-PDT活性。总之，本研究为化疗-光动力协同治疗乳腺癌提供了一种新的策略。

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

Colloids and Surfaces B: Biointerfaces 生物-材料科学：生物材料

CiteScore

11.10

自引率

3.40%

发文量

730

审稿时长

42 days

期刊介绍： Colloids and Surfaces B: Biointerfaces is an international journal devoted to fundamental and applied research on colloid and interfacial phenomena in relation to systems of biological origin, having particular relevance to the medical, pharmaceutical, biotechnological, food and cosmetic fields. Submissions that: (1) deal solely with biological phenomena and do not describe the physico-chemical or colloid-chemical background and/or mechanism of the phenomena, and (2) deal solely with colloid/interfacial phenomena and do not have appropriate biological content or relevance, are outside the scope of the journal and will not be considered for publication. The journal publishes regular research papers, reviews, short communications and invited perspective articles, called BioInterface Perspectives. The BioInterface Perspective provide researchers the opportunity to review their own work, as well as provide insight into the work of others that inspired and influenced the author. Regular articles should have a maximum total length of 6,000 words. In addition, a (combined) maximum of 8 normal-sized figures and/or tables is allowed (so for instance 3 tables and 5 figures). For multiple-panel figures each set of two panels equates to one figure. Short communications should not exceed half of the above. It is required to give on the article cover page a short statistical summary of the article listing the total number of words and tables/figures.