Novel silk fibroin nanoparticles incorporated silk fibroin hydrogel for inhibition of cancer stem cells and tumor growth.

Abstract

BACKGROUND:

A multi-drug delivery platform is needed as the intra-tumoral heterogeneity of cancer leads to different drug susceptibility. Cancer stem cells (CSCs), a small population of tumor cells responsible for tumor seeding and recurrence, are considered chemotherapy-resistant and have been reported to be sensitive to salinomycin (Sal) instead of paclitaxel (Ptx). Here we report a novel silk fibroin (SF) hydrogel-loading Sal and Ptx by incorporating drug-loaded silk fibroin nanoparticles (SF-NPs) to simultaneously kill CSCs and non-CSCs.

METHODS:

Using the method we have previously reported to prepare Ptx-loaded SF-NPs (Ptx-SF-NPs), Sal-loaded SF-NPs (Sal-SF-NPs) were fabricated under mild and non-toxic conditions. The drug-loaded SF-NPs were dispersed in the ultrasound processed SF solution prior to gelation.

RESULTS:

The resulting SF hydrogel (Sal-Ptx-NP-Gel) retained its injectable properties, exhibited bio-degradability and demonstrated homogeneous drug distribution compared to the non-NP incorporated hydrogel. Sal-Ptx-NP-Gel showed superior inhibition of tumor growth compared to single drug-loaded hydrogel and systemic dual drug administration in the murine hepatic carcinoma H22 subcutaneous tumor model. Sal-Ptx-NP-Gel also significantly reduced CD44+CD133+ tumor cells and demonstrated the least tumor formation in the in vivo tumor seeding experiment, indicating superior inhibition of cancer stem cells.

CONCLUSION:

These results suggest that SF-NPs incorporated SF hydrogel is a promising drug delivery platform, and Sal-Ptx-NP-Gel could be a novel and powerful locoregional tumor treatment regimen in the future.

• Authors: Puyuan Wu, Qin Liu, Qin Wang, Hanqing Qian, Lixia Yu, Baorui Liu, Rutian Li
• Journal: International journal of nanomedicine (Int J Nanomedicine) Vol. 13 Pg. 5405-5418 ( 2018) ISSN: 1178-2013 [Electronic] New Zealand
• PMID: 30271137 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Hydrogels
• Pyrans
• salinomycin
• Fibroins
• Paclitaxel

Topics

• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Drug Delivery Systems
• Drug Liberation
• Fibroins (chemistry)
• Humans
• Hydrogels (chemistry)
• Male
• Mice, Inbred ICR
• Nanoparticles (chemistry, toxicity, ultrastructure)
• Neoplastic Stem Cells (drug effects, pathology)
• Paclitaxel (pharmacology, therapeutic use)
• Pyrans (pharmacology, therapeutic use)
• Toxicity Tests