A Biodegradable Multifunctional Graphene Oxide Platform for Targeted Cancer Therapy

被引:57
作者
Martin, Cristina [1 ]
Ruiz, Amalia [1 ]
Keshavan, Sandeep [2 ]
Reina, Giacomo [1 ]
Murera, Diane [1 ]
Nishina, Yuta [3 ,4 ]
Fadeel, Bengt [2 ]
Bianco, Alberto [1 ]
机构
[1] Univ Strasbourg, CNRS, Immunol Immunopathol & Therapeut Chem, UPR 3572, F-67000 Strasbourg, France
[2] Karolinska Inst, Inst Environm Med, S-17177 Stockholm, Sweden
[3] Okayama Univ, Grad Sch Nat Sci & Technol, Kita Ku, Okayama 7008530, Japan
[4] Okayama Univ, Res Core Interdisciplinary Sci, Kita Ku, Okayama 7008530, Japan
关键词
biodegradation; cancer; chemoattractants; drug delivery; graphene; WALLED CARBON NANOTUBES; CONTROLLED-RELEASE; DOXORUBICIN; DEGRADATION; STABILITY; DELIVERY; NANOTECHNOLOGY; NANOMATERIALS; NEUTROPHILS; MECHANISMS;
D O I
10.1002/adfm.201901761
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The design of multifunctional materials able to both selectively deliver a drug into cells in a targeted manner and display an enhanced propensity for biodegradation is an important goal. Here, graphene oxide (GO) is functionalized with the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP) known to interact with the formyl peptide receptor, which is expressed in different cancer cells, including cervical carcinoma cells. This study highlights the ability of GOfMLP for targeted drug delivery and cancer cell killing and the subsequent degradation capacity of the hybrid. Biodegradation is assessed via Raman spectroscopy and transmission electron microscopy. The results show that GOfMLP is susceptible to faster myeloperoxidase-mediated degradation. The hybrid material, but not GO, is capable of inducing neutrophil degranulation with subsequent degradation, being the first study showing inducible neutrophil degradation by the nanomaterial itself with no prior activation of the cells. In addition, confocal imaging and flow cytometry using HeLa cells demonstrate that GOfMLP is able to deliver the chemotherapeutic agent doxorubicin faster into cells, inducing higher levels of apoptosis, when compared to nonfunctionalized GO. The results reveal that GOfMLP is a promising carrier able to efficiently deliver anticancer drugs, being endowed with the ability to induce its own biodegradation.
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页数:11
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