文章目录

长效IL-2通过压力融合生物矿化片剂缓释增强抗肿瘤免疫应答

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

原文发布日期: 2025-06-10

英文摘要:

摘要翻译：

原文链接:

文章 :

长效IL-2通过压力融合生物矿化片剂缓释增强抗肿瘤免疫应答

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

原文发布日期: 2025-06-10

英文摘要:

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.

摘要翻译：

长效可控药物递释制剂对于增强疗效和降低给药频率具有重要临床价值。本研究通过碳酸钙与磷酸钙非晶相的融合及界面消除，构建了一种动力学可控的白介素-2（IL-2）长期缓释平台。与简单混合物不同，我们在2 GPa高压下制备出一组化学式为Ca(CO3)x(PO4)2(1−x)/3（CaCPs，0 < x < 1）的杂化生物矿物。该材料通过结晶驱动释放的特性优化了IL-2的体内命运，其中Ca(CO3)1/2(PO4)1/3能动态重塑免疫抑制性肿瘤微环境：通过改善IL-2的体内再分布，优先激活细胞毒性T细胞和记忆T细胞，在实现肿瘤部位IL-2数周滞留的同时保持良好耐受性和生物安全性。在雌性小鼠黑色素瘤模型中，该材料展现出卓越的抗肿瘤效果——不仅能抑制局部肿瘤复发、阻滞远端未治疗肿瘤的生长，还能维持针对再攻击转移瘤的长期T细胞免疫应答。