Pharmaceutical Research

, 35:63 | Cite as

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

Research Paper
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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.

Key words

anticancer bioorthogonal chemistry mesoporous silica nanoparticle pre-targeting ruthenium complex 

Abbreviations

BJH

Barrett–Joyner–Halenda

DAPI

4′,6-diamidino-2-phenylindole

DBCO

Aza-dibenzocyclooctynes

EPR

Enhanced permeability and retention

ESI-MS

Electrospray ionization mass

FITC-N3

1-(3-azidopropyl) fluorescein

FT-IR

Flourier transform infrared spectra

GSH

Glutathione

HPLC

High performance liquid chromatography

MMP

Mitochondrial membrane potential

MSNs

Mesoporous silica nanoparticles

MTT

3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide

N3-OH

2-Azidoethanol

N3-S-S-NHC-Ru

2-azidoethyl (2-((2-hydroxyethyl)disulfanyl)ethyl) N-heterocyclic carbene ruthenium complex

NHC-Ru

N-heterocyclic carbene ruthenium complex

NMR

Nuclear magnetic resonance

PBS

Phosphate-buffered saline

SPAAC

Strain-promoted alkyne azide cycloaddition

TEM

Transmission electron microscopy

Notes

ACKNOWLEDGMENTS AND DISCLOSURES

This work was financially supported by National Natural Science Foundation of China (21501074 and 21371082), Natural Science Foundation of Jiangsu Province (BK20151118), the 333 Project of Jiangsu Province (BRA2016518) and the Key Youth Medical Talent Project of Jiangsu Province (QNRC20162016626 and QNRC20162016629).

Supplementary material

11095_2017_2338_MOESM1_ESM.docx (1.5 mb)
ESM 1 (DOCX 1507 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear MedicineJiangsu Institute of Nuclear MedicineWuxiChina

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