Liver-Specific Nanoparticle-Mediated Delivery and MMP-Triggered Release of Veratridine to Effectively Target Metastatic Colorectal Cancer
Abstract
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Instrumentation
2.3. MSN Synthesis and Surface Functionalization
2.4. Drug Loading, Casein Attachment, and Stimuli-Triggered Drug Release with MSN-COOH
2.5. Synthesis of CaCO3 Particles, Drug Loading, Skim Milk Coating, and Drug Release
2.6. Cell Culture
2.7. Western Blot
2.8. Crystal Assay and Immunofluorescence Staining
2.9. Human Apoptosis Antibody Array
2.10. Assessment of Apoptosis
2.11. Nanoparticle Sterility
2.12. Animals and Preparation
2.13. Murine Mouse Model of Colorectal Cancer
2.14. Xenograft Mouse Model of Colorectal Cancer
2.15. Orthotopic Implantation of Cells for a Splenolepatic Mouse Model of Metastatic Colorectal Cancer (CRC)
2.16. Statistical Analysis
3. Results
3.1. Veratridine (VTD), a Novel Small Anti-Cancer Molecule, Induces Apoptosis via Intrinsic and Extrinsic Pathways
3.2. Veratridine Suppresses Tumor Progression in an AOM/DSS Mouse Colon Cancer Model in a UBXN2A-Dependent Manner
3.3. Pristine and Functionalized MSNs: Synthesis and Characterization
3.4. VTD Loading, Casein Coupling, and MMP-7 and 9-Responsive VTD Releasing
3.5. Tumor Suppressive Effect of MMP-Responsive Nanoparticles in a CRC Xenograft Model
3.6. MSN-COOH/VTD/CAS (VTD, 0.2 mg/kg) Target and Suppress Metastatic Tumors in an Orthotopic Splenolepatic Mouse Model of CRC
3.7. Calcium Carbonate Microparticles (CCMPs) and Calcium Carbonate Submicroparticles (CCSMPs): Improved Carriers for VTD Delivery
4. Discussion
5. Conclusions
6. Patents
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
VTD | Veratridine |
CAS | Casein |
MSNs | Mesoporous silica nanoparticles |
CCMPs | Calcium carbonate microparticles |
MMPs | Matrix Metalloproteinases |
CRC | Colorectal cancer |
NP-VTD | MSN-COOH/VTD/CAS |
NP-Empty | MSN-COOH/EMPTY/CAS |
CCSMPs | Calcium carbonate submicroparticles |
AOM/DSS | azoxymethane/dextran sodium sulfate |
UBXN2A (+/−) | heterozygous haploinsufficient UBXN2A |
MSN-NH2 | Aminated mesoporous silica nanoparticles |
MSN-COOH | Carboxylated mesoporous silica nanoparticles |
APTES | 3-aminopropyltriethoxysilane |
EDC | 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide |
CTAB | Cetyltrimethylammonium bromide |
TEOS | tetraethyl orthosilicate |
DMF | Dimethy formamide |
BSA | Bovine serum albumin |
BET | Brunauer–Emmett–Teller |
NIR | Near-infrared |
BJH | Barrett-Joyner-Halenda |
HPLC | High performance liquid chromatography |
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Hasan, M.; Eikanger, M.; Sane, S.; Wijewardhane, K.S.K.; Slunecka, J.L.; Freeling, J.; Rezvani, K.; Sereda, G. Liver-Specific Nanoparticle-Mediated Delivery and MMP-Triggered Release of Veratridine to Effectively Target Metastatic Colorectal Cancer. Cancers 2025, 17, 3253. https://doi.org/10.3390/cancers17193253
Hasan M, Eikanger M, Sane S, Wijewardhane KSK, Slunecka JL, Freeling J, Rezvani K, Sereda G. Liver-Specific Nanoparticle-Mediated Delivery and MMP-Triggered Release of Veratridine to Effectively Target Metastatic Colorectal Cancer. Cancers. 2025; 17(19):3253. https://doi.org/10.3390/cancers17193253
Chicago/Turabian StyleHasan, Mahadi, Morgan Eikanger, Sanam Sane, Krishantha S. K. Wijewardhane, John L. Slunecka, Jessica Freeling, Khosrow Rezvani, and Grigoriy Sereda. 2025. "Liver-Specific Nanoparticle-Mediated Delivery and MMP-Triggered Release of Veratridine to Effectively Target Metastatic Colorectal Cancer" Cancers 17, no. 19: 3253. https://doi.org/10.3390/cancers17193253
APA StyleHasan, M., Eikanger, M., Sane, S., Wijewardhane, K. S. K., Slunecka, J. L., Freeling, J., Rezvani, K., & Sereda, G. (2025). Liver-Specific Nanoparticle-Mediated Delivery and MMP-Triggered Release of Veratridine to Effectively Target Metastatic Colorectal Cancer. Cancers, 17(19), 3253. https://doi.org/10.3390/cancers17193253