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<p>Cyclic molecular architectures offer unparalleled functional diversity and assembly advantages, holding significant promise for applications in nanomedicine. Herein, we propose a cyclic molecular engineering strategy designed to address the hydrophobicity of organic dyes while simultaneously enhancing their phototherapeutic efficacy. Through esterification of the boron dipyrromethene (BDP) core with adipic acid (CB-c) or dithiodiacetic acid (CB-s), we developed self-assembling nanoparticles (NPs) with exceptional colloidal stability (&gt;60 d) and microenvironment-responsive dissociation. CB-s NPs exhibited unique antiparallel dimeric packing in crystallographic studies, enabling robust H-aggregation. The redox-sensitive disulfide bonds in CB-s NPs conferred tumor-selective disassembly (90% dissociation within 30 h), facilitating spatiotemporally controlled therapeutic activation. <i>In vivo</i> studies demonstrated superior synergistic photodynamic/photothermal therapy (PDT/PTT) efficacy, achieving 92% tumor suppression. This work establishes cyclic architecture-driven supramolecular organization as a paradigm-shifting approach for developing multifunctional nanomaterials.</p>

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Intrinsic cyclic boron dipyrromethene nanoparticles with tumor-activated disassembly for enhanced phototherapeutic stability and efficacy

  • 期刊论文

  • 发表日期：

    2026年3月10日

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  • Aoqing Jia,
  • Zhen Yang,
  • Zhigang Xie,
  • Min Zheng

摘要

Cyclic molecular architectures offer unparalleled functional diversity and assembly advantages, holding significant promise for applications in nanomedicine. Herein, we propose a cyclic molecular engineering strategy designed to address the hydrophobicity of organic dyes while simultaneously enhancing their phototherapeutic efficacy. Through esterification of the boron dipyrromethene (BDP) core with adipic acid (CB-c) or dithiodiacetic acid (CB-s), we developed self-assembling nanoparticles (NPs) with exceptional colloidal stability (>60 d) and microenvironment-responsive dissociation. CB-s NPs exhibited unique antiparallel dimeric packing in crystallographic studies, enabling robust H-aggregation. The redox-sensitive disulfide bonds in CB-s NPs conferred tumor-selective disassembly (90% dissociation within 30 h), facilitating spatiotemporally controlled therapeutic activation. In vivo studies demonstrated superior synergistic photodynamic/photothermal therapy (PDT/PTT) efficacy, achieving 92% tumor suppression. This work establishes cyclic architecture-driven supramolecular organization as a paradigm-shifting approach for developing multifunctional nanomaterials.