Transforming malignant tumors into vulnerable phenotypes via nanoscale coordination polymer mediated cell senescence and photodynamic therapy

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials Pub Date : 2025-04-22 DOI:10.1016/j.biomaterials.2025.123355

Wenyao Zhen , Xiaomin Jiang , En Li , Tomas Germanas , Morten J. Lee , Taokun Luo , Xin Ma , Chaoyu Wang , Yimei Chen , Ralph R. Weichselbaum , Wenbin Lin

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引用次数: 0

Abstract

Induction of senescence in cancer cells can thwart the proliferation of malignant tumors. Herein we report the design of AZT-P/pyro nanoscale coordination polymer particles consisting of 3-azido-2,3-dideoxythymidine monophosphate (AZT-P) in the core and photosensitizing pyro-lipid (pyro) in the shell for potent antitumor treatment. Gradual release of AZT-P in response to an acidic tumor microenvironment transforms cancer cells with unlimited proliferation capacity into senescent cells that are vulnerable to reactive oxygen species (ROS). Pyro selectively induces ROS generation and immunogenic cell death of cancer cells upon light irradiation. Co-delivery of AZT-P and pyro in a single particle prolongs their blood circulation times and enhances their accumulation in tumors. Additionally, the induction of senescence and ROS generation both contribute to the recruitment of immune cells to the tumors, resulting in an effective immune response to inhibit the growth of large subcutaneous tumors and metastatic spread of orthotopic tumors.

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通过纳米配位聚合物介导的细胞衰老和光动力疗法将恶性肿瘤转化为易损表型

诱导癌细胞衰老可以阻止恶性肿瘤的增殖。在此，我们设计了AZT-P/pyro纳米级配位聚合物颗粒，该聚合物由3-叠氮-2,3-二脱氧胸腺嘧啶单磷酸（AZT-P）组成，其核心为光敏性热脂（pyro），具有有效的抗肿瘤治疗作用。AZT-P在酸性肿瘤微环境下的逐渐释放，将具有无限增殖能力的癌细胞转化为易受活性氧（ROS）攻击的衰老细胞。在光照射下，Pyro选择性地诱导癌细胞产生ROS和免疫原性细胞死亡。AZT-P和pyro在单个颗粒中共同递送，延长了它们的血液循环时间，并增加了它们在肿瘤中的蓄积。此外，衰老的诱导和ROS的产生都有助于免疫细胞向肿瘤募集，从而产生有效的免疫反应，抑制大皮下肿瘤的生长和原位肿瘤的转移扩散。

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.