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<p>The cross-cutting field of cancer immunotherapy triggered by immunogenic cell death (ICD) has made encouraging achievements; however, such a research field is often hampered by deficient ICD-inducing efficacy due to low tumor-targeting and insufficient drug concentration in tumor cells. With these issues in mind, an active tumor targeting hydrogen-bonded (H-bonded) intelligent supramolecular polymeric nanomedicine FT/FOF@PDOB is constructed, featuring synergetic sonodynamic and chemotherapy (SDT/CT), and amplified ICD-inducing efficacy with strengthened immunological potency. To do so, an active-targeting six-arm star-shaped amphiphilic random copolymer vehicle, PDOB, is developed, comprising a biotin-mediated active tumor targeting regime, and diaminopyridine (DAP) motifs bearing hetero-complementary H-bonding array towards 5-fluorouracil (FU) moieties. The high-fidelity of H-bonding modularity from privileged DAP/FU pair enables specific binding interaction and co-loading of both FU-functionalized tetraphenylporphyrin-based sonosensitizer FT, and α,ω-FU-functionalized oxaliplatin-based symmetrical fuplatin dual-prodrug FOF. Consequently, H-bonded active-targeting nanomedicine FT/FOF@PDOB is readily fabricated, characterized by enhanced cargo uploading content and pH-responsive drug release, therefore endowing the synergetic therapy via FT-induced SDT and FOF-based CT, also facilitating the enhanced ICD effect and stronger anti-tumor immunity. Both <i>in vitro</i> and <i>in vivo</i> therapeutic regimes with outstanding anti-tumor outcomes are truly accomplished. The privileged advantages offered by H-bond design constitute a rising arsenal towards multimodal combination immunotherapy.</p>

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Allies against the adversary: active-targeting hydrogen-bonded immunogenic nanomedicine for multimodal conquering of cancer cells

  • 期刊论文

  • 发表日期：

    2026年4月7日

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  • Yanggui Wu,
  • Ting Li,
  • Zeke Li,
  • Senbin Chen,
  • Jintao Zhu

摘要

The cross-cutting field of cancer immunotherapy triggered by immunogenic cell death (ICD) has made encouraging achievements; however, such a research field is often hampered by deficient ICD-inducing efficacy due to low tumor-targeting and insufficient drug concentration in tumor cells. With these issues in mind, an active tumor targeting hydrogen-bonded (H-bonded) intelligent supramolecular polymeric nanomedicine FT/FOF@PDOB is constructed, featuring synergetic sonodynamic and chemotherapy (SDT/CT), and amplified ICD-inducing efficacy with strengthened immunological potency. To do so, an active-targeting six-arm star-shaped amphiphilic random copolymer vehicle, PDOB, is developed, comprising a biotin-mediated active tumor targeting regime, and diaminopyridine (DAP) motifs bearing hetero-complementary H-bonding array towards 5-fluorouracil (FU) moieties. The high-fidelity of H-bonding modularity from privileged DAP/FU pair enables specific binding interaction and co-loading of both FU-functionalized tetraphenylporphyrin-based sonosensitizer FT, and α,ω-FU-functionalized oxaliplatin-based symmetrical fuplatin dual-prodrug FOF. Consequently, H-bonded active-targeting nanomedicine FT/FOF@PDOB is readily fabricated, characterized by enhanced cargo uploading content and pH-responsive drug release, therefore endowing the synergetic therapy via FT-induced SDT and FOF-based CT, also facilitating the enhanced ICD effect and stronger anti-tumor immunity. Both in vitro and in vivo therapeutic regimes with outstanding anti-tumor outcomes are truly accomplished. The privileged advantages offered by H-bond design constitute a rising arsenal towards multimodal combination immunotherapy.