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<p>Since proximal enzymes promote cancer metabolism, proximal enzymes-targeted polymers can be an attractive strategy in nanomedicine. We previously reported the chain length of polymers targeting carbonic anhydrase IX and matrix metalloproteinase 14 (PGA-UTs) contributed to the synergistic inhibition of cancer cell proliferation in 2D culture. Here, we investigated the influence of PGA-UT chain length on the targeting efficiency, cytotoxicity, and selectivity on heterotypic three-dimensional multicellular tumor spheroids composed of human breast cancer cells and fibroblasts. PGA-UT with 200-mer showed higher spheroid penetration and cytotoxicity compared to an 800-mer. This study provides insights into designing polymer-based multivalent ligands for cancer therapy.</p> Graphical Abstract <p></p>

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Contribution of chain length of proximal enzymes-targeted polymers to inhibitory effect on three-dimensional multicellular tumor spheroids

  • 期刊论文

  • 发表日期：

    2025年7月25日

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  • Yuki Koba,
  • Masahiko Nakamoto,
  • Séverine Domenichini,
  • Juliette Vergnaud,
  • Mélanie Hery,
  • Simona Mura,
  • Michiya Matsusaki

摘要

Since proximal enzymes promote cancer metabolism, proximal enzymes-targeted polymers can be an attractive strategy in nanomedicine. We previously reported the chain length of polymers targeting carbonic anhydrase IX and matrix metalloproteinase 14 (PGA-UTs) contributed to the synergistic inhibition of cancer cell proliferation in 2D culture. Here, we investigated the influence of PGA-UT chain length on the targeting efficiency, cytotoxicity, and selectivity on heterotypic three-dimensional multicellular tumor spheroids composed of human breast cancer cells and fibroblasts. PGA-UT with 200-mer showed higher spheroid penetration and cytotoxicity compared to an 800-mer. This study provides insights into designing polymer-based multivalent ligands for cancer therapy.

Graphical Abstract