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Updated: Feb 4, 2026

Microfluidic-based Synthesis of Covalent Organic Frameworks COFs: A Tool for Continuous Production of COF Fibers and Direct Printing on a Surface
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Microfluidic-based Synthesis of Covalent Organic Frameworks COFs: A Tool for Continuous Production of COF Fibers and Direct Printing on a Surface

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Overcoming Chemoresistance via an AIEgen-Based Covalent Organic Framework

An Song1,2, Qing Wang1, Bo-Yu Liu3

  • 1State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan 430079, China.

Nano Letters
|February 2, 2026
PubMed

Insights

A novel covalent organic framework (COF) nanomedicine effectively targets chemoresistant cancers by suppressing cancer stemness and immune suppression. This breakthrough nanomedicine shows significant potential for treating recurrent tumors and improving patient outcomes.

Area of Science:

  • Biomedical Engineering
  • Materials Science
  • Cancer Research

Background:

  • Chemoresistance is a significant obstacle in cancer therapy, leading to treatment failure, tumor recurrence, and increased mortality.
  • Effective strategies are urgently needed to overcome chemoresistance and improve patient survival rates.

Purpose of the Study:

  • To develop and evaluate a novel covalent organic framework (COF) nanomedicine, 3N-DPQ-COF, for targeting and treating chemoresistant cancers.
  • To investigate the mechanisms by which 3N-DPQ-COF overcomes chemoresistance, including its effects on cancer stemness, the tumor microenvironment (TME), and immune activation.

Main Methods:

  • Synthesis and characterization of the AIEgen-based COF nanomedicine, 3N-DPQ-COF.
  • In vitro and in vivo evaluation of 3N-DPQ-COF in chemoresistant 4T1 and CT26 cancer models.
  • Assessment of 3N-DPQ-COF's impact on cancer stemness, TME composition (CD8+ T cells, myeloid-derived suppressor cells, erythroid progenitor cells), and pyroptosis induction (GSDME-dependent).

Main Results:

  • 3N-DPQ-COF demonstrated efficient accumulation in resistant tumor cells and suppressed cancer stemness, outperforming doxorubicin in 4T1 and CT26 models.
  • The nanomedicine promoted CD8+ T-cell infiltration, reduced immunosuppressive cells, and induced GSDME-dependent pyroptosis, effectively remodeling the TME.
  • Remarkably, 3N-DPQ-COF suppressed metastasis and recurrence in chemoresistant tumors, achieving over 90% tumor inhibition and cure rates exceeding 80% without checkpoint blockade.

Conclusions:

  • AIEgen-based COF nanomedicines, exemplified by 3N-DPQ-COF, offer a promising strategy for overcoming chemoresistance.
  • Concurrent modulation of tumor stemness, pyroptosis, and immune activation by 3N-DPQ-COF presents a potent approach for cancer treatment.
  • This study underscores the therapeutic potential of advanced nanomedicines in addressing critical challenges in oncology, including metastasis and recurrence.
Keywords:
aggregation-induced emissioncancer immunotherapychemoresistancecovalent organic frameworkpyroptosis

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