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Background <p>Radioactive isotopes, such as Indium-111 (<sup>111</sup>In), are pivotal for highly sensitive noninvasive imaging and targeted radiotherapy. However, achieving stable in vivo retention remains a critical barrier. Conventional nanocarriers typically rely on surface-bound chelators, exposing the isotopes to biological transchelation and detachment, while potentially altering the carrier’s surface properties and pharmacokinetics. To address these limitations, this study evaluates a polyionic complex micelle (PICm) platform designed to encapsulate <sup>111</sup>In within a crosslinked core using DOTA chelation. This approach aims to enhance radiochemical stability while preserving the micelle’s native, engineered surface characteristics.</p> Results <p>DOTA-functionalized PICm were fabricated through electrostatic self-assembly of PEG-based polymers and subsequent core crosslinking. The resulting micelles exhibited a highly uniform size (32.6 ± 6.3 nm) and a modestly negative surface charge (−&#xa0;4.9 ± 1.0 mV). Stability assays demonstrated that under the acidic conditions required for <sup>111</sup>In chelation (pH 5.5), the micelles undergo reversible size swelling driven by polymer protonation without aggregating or collapsing, confirming that core crosslinking successfully maintains micellar integrity. In vivo biodistribution in CT26 tumor-bearing mice revealed that <sup>111</sup>In-loaded PICm displayed prolonged systemic presence, with tumor accumulation peaking at 2.3 ± 0.4%ID/g at 24&#xa0;h post-injection via the enhanced permeability and retention effect. Hepatic and splenic uptakes aligned with typical nanoparticle clearance pathways.</p> Conclusions <p>The core-loading of PICm may offer advantages over surface-chelated nanocarriers. By maintaining structural integrity during radiolabeling and extending systemic circulation in vivo, these results validate the platform’s robustness and passive tumor accumulation, highlighting its potential as a versatile vehicle for the delivery of diagnostic radionuclides.</p>

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Stable core-encapsulation of indium-111 in crosslinked polyionic complex micelles and assessment of its biodistribution

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月4日

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  • Hayato Laurence Mizuno,
  • Sotaro Miyao,
  • Hiroyuki Takahashi,
  • Nobuyoshi Akimitsu,
  • Yasutaka Anraku

摘要

Background

Radioactive isotopes, such as Indium-111 (111In), are pivotal for highly sensitive noninvasive imaging and targeted radiotherapy. However, achieving stable in vivo retention remains a critical barrier. Conventional nanocarriers typically rely on surface-bound chelators, exposing the isotopes to biological transchelation and detachment, while potentially altering the carrier’s surface properties and pharmacokinetics. To address these limitations, this study evaluates a polyionic complex micelle (PICm) platform designed to encapsulate 111In within a crosslinked core using DOTA chelation. This approach aims to enhance radiochemical stability while preserving the micelle’s native, engineered surface characteristics.

Results

DOTA-functionalized PICm were fabricated through electrostatic self-assembly of PEG-based polymers and subsequent core crosslinking. The resulting micelles exhibited a highly uniform size (32.6 ± 6.3 nm) and a modestly negative surface charge (− 4.9 ± 1.0 mV). Stability assays demonstrated that under the acidic conditions required for 111In chelation (pH 5.5), the micelles undergo reversible size swelling driven by polymer protonation without aggregating or collapsing, confirming that core crosslinking successfully maintains micellar integrity. In vivo biodistribution in CT26 tumor-bearing mice revealed that 111In-loaded PICm displayed prolonged systemic presence, with tumor accumulation peaking at 2.3 ± 0.4%ID/g at 24 h post-injection via the enhanced permeability and retention effect. Hepatic and splenic uptakes aligned with typical nanoparticle clearance pathways.

Conclusions

The core-loading of PICm may offer advantages over surface-chelated nanocarriers. By maintaining structural integrity during radiolabeling and extending systemic circulation in vivo, these results validate the platform’s robustness and passive tumor accumulation, highlighting its potential as a versatile vehicle for the delivery of diagnostic radionuclides.