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Post-Synthetic Modification Nanoscale Metal-Organic Frameworks for Targeted Drug Delivery in Cancer Cells

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Abstract

Purpose

Metal-organic frameworks (MOFs) have shown great potentials as drug delivery carriers, but the conventional methods for MOFs synthesis limited their use in biomedicine. The aim of this study was engineered tumor-targeted zinc nanoscale MOFs encapsulating chemotherapy drug.

Methods

We employed post-synthetic modification to construct tumor cell-targeted nanoscale zinc MOFs (nanoMOFs) functionalized with folate as the targeting ligand that binds specifically to folate receptors on tumor cells. The cytoctoxicity of drug-loaded nanoMOFs was measured by MTT assay. The cell target was tested by cell compete assay.

Results

The successful synthesis of folate-targeted nanoMOFs was confirmed by FTIR, 1H-NMR and ESI-MS analysis. In the drug loading test, the zinc nanoMOFs functionalized with folate quickly adsorbed up to 24 wt % 5-fluorouracil (5-FU) without causing obvious changes in the supramolecular crystalline organization of the material. The in vitro drug release profile of this nanoMOFs in phosphate buffered saline exhibited a biphasic pattern. The drug sustained release is the effect mainly of diffusion of 5-FU molecules, while the degradation of the carrier itself plays a minor role in this process. The drug-loaded nanoMOFs showed a stronger cytotoxicity than free 5-FU against three cancer cell lines in vitro with a distinct selectivity between folate receptors positive and negative cells.

Conclusions

These results encourage further in vivo studies of this nanoMOFs as candidates for tumor-targeted, sustained-release delivery of chemotherapeutic agents.

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Abbreviations

5-FU:

5-fluorouracil

1 H NMR :

Proton nuclear magnetic resonance

ATCC :

American Type Culture Collection

CHCl 3 :

chloroform

DCC :

N,N’-dicyclohexylcarbodiimide

DMF :

Dimethyl formamide

DMSO :

Dimethylsulf-oxide

EA :

Elemental analysis

ESI-MS :

Electrospray ionization-mass spectrometry

FA-IRMOF-3 :

Folate-targeted zinc-based nanoMOFs

FBS :

Fetal bovine serum

FE-SEM :

Field emission scanning electron microscopy

FR :

Folate receptors

FT-IR :

Fourier transform infrared

HPLC :

High-performance liquid chromatography

IRMOF-3 :

Zn4O(C8H5NO4)3

MOFs:

Metal-organic frameworks

MTT :

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

nanoMOFs :

Nanosized MOFs

NH 2 -BDC :

2-Aminobenzene-1,4-dicarboxylic acid

PBS :

Phosphate buffered saline

PXRD :

Powder X-ray diffraction

SPSS :

Statistical Package for the Social Sciences

TGA :

Thermogravimetric analysis

UV :

Ultraviolet spectrophotometry

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Acknowledgments and Disclosures

This work was funded by a Grant from the Science and Technology Planning Project of Guangdong Province (2014A010105026). This work was partially supported by grants from the National Natural Science Foundation of China (Grant 21,201,044), the Chinese Training Plan of Guangdong Province Outstanding Young Professors in Higher Education Institutions (GrantYQ2013084).

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Author notes

  1. Baochun Yang and Mei Shen contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacy, Nanfang Hospital, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China

    Baochun Yang & Fei Ren

  2. Department of Inspection and Quarantine (Hygiene Detection Center), Southern Medical University, Guangzhou, 510515, China

    Mei Shen

  3. School of Pharmacy, Guangdong Medical University, Dongguan, 523808, China

    Jianqiang Liu

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  1. Baochun Yang
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Correspondence to Fei Ren.

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Yang, B., Shen, M., Liu, J. et al. Post-Synthetic Modification Nanoscale Metal-Organic Frameworks for Targeted Drug Delivery in Cancer Cells. Pharm Res 34, 2440–2450 (2017). https://doi.org/10.1007/s11095-017-2253-9

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  • DOI: https://doi.org/10.1007/s11095-017-2253-9

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