加压生物矿物质片释放长效IL-2促进抗肿瘤免疫反应。

IF 23.5 1区医学 Q1 ONCOLOGY

Nature cancer Pub Date : 2025-06-10 DOI:10.1038/s43018-025-00993-4

Jinpeng Han, Shenqiang Wang, Weifeng Fang, Yinxian Yang, Ruyi Zhou, Yuqi Zhang, Jicheng Yu, Ruikang Tang, Zhaoming Liu, Zhen Gu

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引用次数: 0

摘要

人们迫切需要长效控释制剂，以增强疗效和减少给药频率。在这里，我们提出了一个动态可控的长期白介素-2 （IL-2）释放平台，通过融合和边界消除碳酸钙和磷酸钙的非晶态相。与混合物不同，一组化学式为Ca(CO3)x(PO4)2(1-x)/3 (CaCPs, 0.3)1/2(PO4)1/3的混合生物矿物质动态重塑了免疫抑制的肿瘤微环境，通过改善IL-2再分配优先激活细胞毒性和记忆性T细胞，并在具有高耐受性和生物安全性的肿瘤中实现了长达数周的IL-2保留。在雌性小鼠黑色素瘤模型中，Ca(CO3)1/2(PO4)1/3显示出优异的抗肿瘤作用，可以抑制局部肿瘤复发，阻碍远处未治疗肿瘤的生长，并维持长期的T细胞对再挑战转移性肿瘤的反应。

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Long-acting IL-2 release from pressure-fused biomineral tablets promotes antitumor immune response.

Long-acting controlled drug release formulations are highly desired for potentiating efficacy and reducing administration frequency. Here we present a kinetically controllable long-term interleukin-2 (IL-2) release platform by the fusion and boundary elimination of calcium carbonate and calcium phosphate amorphous phases. Unlike mixtures, a group of hybrid biominerals with the chemical formula Ca(CO₃)_x(PO₄)_2(1-x)/3 (CaCPs, 0 < x < 1) was fabricated under high pressure (2 GPa), and the CaCPs showed crystallization-driven release behaviors to optimize the in vivo fate of IL-2. Ca(CO₃)_1/2(PO₄)_1/3 dynamically remodeled immunosuppressive tumor microenvironments, preferentially activated cytotoxic and memory T cells by improving IL-2 redistribution and achieved weeks-long IL-2 retention in tumors with high tolerance and biosafety. In a melanoma model in female mice, Ca(CO₃)_1/2(PO₄)_1/3 revealed superior antitumor effects to inhibit local tumor recurrence, hinder the growth of distant untreated tumors and maintain long-term T cell responses against the rechallenged metastatic tumors.

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来源期刊

Nature cancer Medicine-Oncology

CiteScore

31.10

自引率

1.80%

发文量

129

期刊介绍： Cancer is a devastating disease responsible for millions of deaths worldwide. However, many of these deaths could be prevented with improved prevention and treatment strategies. To achieve this, it is crucial to focus on accurate diagnosis, effective treatment methods, and understanding the socioeconomic factors that influence cancer rates. Nature Cancer aims to serve as a unique platform for sharing the latest advancements in cancer research across various scientific fields, encompassing life sciences, physical sciences, applied sciences, and social sciences. The journal is particularly interested in fundamental research that enhances our understanding of tumor development and progression, as well as research that translates this knowledge into clinical applications through innovative diagnostic and therapeutic approaches. Additionally, Nature Cancer welcomes clinical studies that inform cancer diagnosis, treatment, and prevention, along with contributions exploring the societal impact of cancer on a global scale. In addition to publishing original research, Nature Cancer will feature Comments, Reviews, News & Views, Features, and Correspondence that hold significant value for the diverse field of cancer research.