Enhanced Tumor Diagnostic and Therapeutic Effect of Mesoporous Silica Nanoparticle-Mediated Pre-targeted Strategy.

Abstract

PURPOSE:

Improving the targeting efficiency of imaging agents or anticancer drugs has become essential in the current primary mission to enhance the diagnostic or therapeutic effects. To improve the tumor diagnosis and therapy effect, a promising drug-delivery and targeting strategy was established based on the bioorthogonal chemistry.

METHOD:

The delivery system was composed of the pre-targeting carrier Biotin-MSNs-DBCO nanoparticles and the azido cargoes. The fluorescence probe 1-(3-azidopropyl) fluorescein (FITC-N3) and ruthenium N-heterocyclic carbene complex N3-S-S-NHC-Ru were synthesized and served as the tumor imaging and therapy probes, respectively. The cell imaging and viability was investigated by the Biotin-MSNs-DBCO pre-targeted for 4 h in colonic carcinoma (HeLa) cells.

RESULTS:

For the tumor cell imaging, Biotin-MSNs-DBCO could react with FITC-N3 rapidly and completely in 20 min with 93% yields. The fluorescence intensity of tumor cells was obviously increased by the Biotin-MSNs-DBCO pre-targeted. The cytotoxicity of the ruthenium complex N3-S-S-NHC-Ru was significantly improved appropriately three times with the IC50 (half inhibitory concentration) value of 6.68 ± 1.29 μM and enhancement of the mitochondrial dysfunction.

CONCLUSIONS:

The pre-targeting nanoparticle Biotin-MSNs-DBCO could selectively capture the azido compounds in tumor cells, which provided a site-specific target for the cargoes and then resulted in an enhancement of diagnostic or therapeutic effects.

• Authors: Gaochao Lv, Ke Li, Ling Qiu, Ying Peng, Xueyu Zhao, Xi Li, Qingzhu Liu, Shanshan Wang, Jianguo Lin
• Journal: Pharmaceutical research (Pharm Res) Vol. 35 Issue 3 Pg. 63 (Feb 14 2018) ISSN: 1573-904X [Electronic] United States
• PMID: 29450652 (Publication Type: Journal Article)

Chemical References

• Aza Compounds
• Cyclooctanes
• Drug Carriers
• Fluorescent Dyes
• Ruthenium Compounds
• Biotin
• Silicon Dioxide
• Fluorescein-5-isothiocyanate

Topics

• Aza Compounds (chemistry)
• Biotin (chemistry)
• Cell Survival (drug effects)
• Cyclooctanes (chemistry)
• Drug Carriers (chemistry)
• Fluorescein-5-isothiocyanate (administration & dosage)
• Fluorescent Dyes (administration & dosage)
• HeLa Cells
• Humans
• Inhibitory Concentration 50
• Intravital Microscopy (methods)
• Membrane Potential, Mitochondrial (drug effects)
• Microscopy, Fluorescence (methods)
• Nanoparticles (chemistry)
• Neoplasms (diagnostic imaging, drug therapy)
• Porosity
• Ruthenium Compounds (administration & dosage)
• Silicon Dioxide (chemistry)