Drug-Free Mesoporous Silica Nanoparticles Enable Suppression of Cancer Metastasis and Confer Survival Advantages to Mice with Tumor Xenografts

Yu Tse Lee, Si Han Wu, Cheng Hsun Wu, Yu Han Lin, Cong Kai Lin, Zih An Chen, Ting Chung Sun, Yin Ju Chen, Peilin Chen, Chung Yuan Mou, Yi Ping Chen*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

Abstract

Despite advancements in nanomedicine for drug delivery, many drug-loaded nanoparticles reduce tumor sizes but often fail to prevent metastasis. Mesoporous silica nanoparticles (MSNs) have attracted attention as promising nanocarriers. Here, we demonstrated that MSN-PEG/TA 25, with proper surface modifications, exhibited unique antimetastatic properties. In vivo studies showed that overall tumor metastasis decreased in 4T1 xenografts mice treated with MSN-PEG/TA 25 with a notable reduction in lung tumor metastasis. In vitro assays, including wound-healing, Boyden chamber, tube-formation, and real-time cell analyses, showed that MSN-PEG/TA 25 could modulate cell migration of 4T1 breast cancer cells and interrupt tube formation by human umbilical vein endothelial cells (HUVECs), key factors in suppressing cancer metastasis. The synergistic effect of MSN-PEG/TA 25 combined with liposomal-encapsulated doxorubicin (Lipo-Dox) significantly boosted mouse survival rates, outperforming Lipo-Dox monotherapy. We attributed the improved survival to the antimetastatic capabilities of MSN-PEG/TA 25. Moreover, Dox-loaded MSN-PEG/TA 25 suppressed primary tumors while retaining the antimetastatic effect, thereby enhancing therapeutic outcomes and overall survival. Western blot and qPCR analyses revealed that MSN-PEG/TA 25 interfered with the phosphorylation of ERK, FAK, and paxillin, thus impacting focal adhesion turnover and inhibiting cell motility. Our findings suggest that drug-free MSN-PEG/TA 25 is highly efficient for cancer treatment via suppressing metastatic activity and angiogenesis.

Original languageEnglish
Pages (from-to)61787-61804
Number of pages18
JournalACS Applied Materials and Interfaces
Volume16
Issue number45
DOIs
StatePublished - 13 11 2024
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2024 The Authors. Published by American Chemical Society.

Keywords

  • angiogenesis
  • cell motility
  • focal adhesion turnover
  • mesoporous silica nanoparticles (MSNs)
  • metastasis
  • Human Umbilical Vein Endothelial Cells
  • Silicon Dioxide/chemistry
  • Breast Neoplasms/pathology
  • Cell Movement/drug effects
  • Humans
  • Xenograft Model Antitumor Assays
  • Drug Carriers/chemistry
  • Animals
  • Polyethylene Glycols/chemistry
  • Lung Neoplasms/drug therapy
  • Nanoparticles/chemistry
  • Cell Line, Tumor
  • Female
  • Mice
  • Mice, Inbred BALB C
  • Porosity
  • Doxorubicin/pharmacology
  • Neoplasm Metastasis/prevention & control

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