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Biomimetic Nano-delivery of Small-Molecule Piceatannol Modulates Tumor Stemness and Suppresses Colorectal Cancer

Minfeng Zhou1, Huifang Niu2,3, Guoquan Huang4,5

  • 1Department of Integrative Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Small (Weinheim an Der Bergstrasse, Germany)
|November 11, 2024
PubMed

Insights

A novel biomimetic nanoparticle system effectively delivers piceatannol (PTL) to inhibit colorectal cancer stem cell metastasis. This targeted therapy suppresses tumor growth by modulating the Hippo/YAP1/SOX9 pathway, offering a promising new strategy.

Area of Science:

  • Biomedical Engineering
  • Oncology
  • Nanotechnology

Background:

  • Colorectal cancer (CRC) metastasis, driven by cancer stem cells (CSCs), significantly reduces patient survival.
  • Current therapies targeting CSCs are limited, and their underlying molecular mechanisms require further elucidation.
  • Developing effective delivery systems for CSC-targeting agents is crucial for improving CRC treatment outcomes.

Purpose of the Study:

  • To develop a biomimetic nanoparticle delivery system for piceatannol (PTL) to suppress colorectal cancer stem cell (CSC) metastasis.
  • To investigate the molecular mechanisms by which PTL affects CSCs and tumor metastasis.
  • To validate the therapeutic efficacy of the developed nanoparticle system in preclinical models.

Main Methods:

  • A biomimetic nanoparticle system (CMD-BHQ3-PTL/DOX@RBCM) was engineered using carboxymethyl dextran (CMD), Black Hole Quencher 3 (BHQ3), PTL, doxorubicin (DOX), and red blood cell membranes (RBCm).
  • Molecular biology experiments, plasmid construction, and high-throughput sequencing were employed to study PTL's effects on CSCs and elucidate molecular pathways.
  • Therapeutic efficacy was assessed in subcutaneous and metastatic tumor models in human and murine systems.

Main Results:

  • The CMD-BHQ3-PTL/DOX@RBCM system demonstrated enhanced specificity and biocompatibility in vivo, effectively inhibiting CSC-related tumor metastasis.
  • PTL's inhibitory effect on metastasis was found to be closely associated with the modulation of the Hippo/YAP1/SOX9 pathway.
  • The pH-responsive nanoparticle system facilitated targeted PTL delivery to tumor sites, highlighting its therapeutic potential.

Conclusions:

  • The developed pH-responsive biomimetic nanoparticle system (CMD-BHQ3-PTL/DOX@RBCM) is effective in delivering PTL for suppressing colorectal cancer stem cell metastasis.
  • The Hippo/YAP1/SOX9 pathway, particularly SOX9, plays a critical role in the mechanism of PTL-mediated anti-metastatic effects.
  • This study presents a promising nanodelivery strategy for targeting CSCs and overcoming therapeutic challenges in colorectal cancer treatment.
Keywords:
biomimetic nano‐delivery systemcancer metastasis Hippo/YAP1/SOX9 pathwaycolorectal cancer stemnesspiceatannol (PTL)

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