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<p>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(CO<sub>3</sub>)<sub><i>x</i></sub>(PO<sub>4</sub>)<sub>2(1−<i>x</i>)/3</sub> (CaCPs, 0 &lt; <i>x</i> &lt; 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(CO<sub>3</sub>)<sub>1/2</sub>(PO<sub>4</sub>)<sub>1/3</sub> 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(CO<sub>3</sub>)<sub>1/2</sub>(PO<sub>4</sub>)<sub>1/3</sub> 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.</p>

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

  • 期刊论文

  • 发表日期：

    2025年6月10日

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

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.