TY - JOUR
T1 - A Biodegradable Multifunctional Graphene Oxide Platform for Targeted Cancer Therapy
AU - Martín, Cristina
AU - Ruiz, Amalia
AU - Keshavan, Sandeep
AU - Reina, Giacomo
AU - Murera, Diane
AU - Nishina, Yuta
AU - Fadeel, Bengt
AU - Bianco, Alberto
N1 - Funding Information:
The authors gratefully acknowledge the financial support from the EU GRAPHENE Flagship project (no. 785219) and the Agence Nationale de la Recherche (ANR) through the LabEx project Chemistry of Complex Systems (ANR-10-LABX-0026_CSC). This work was partly supported by the Centre National de la Recherche Scientifique (CNRS), the International Center for Frontier Research in Chemistry (icFRC), the JST PRESTO, and the JSPS KAKENHI (Science of Atomic Layers (SATL), Grant No. 16H00915). The authors thank C. Royer and V. Demais for TEM analysis at the Plateforme Imagerie in Vitro at the Center of Neurochemistry (Strasbourg, France). The authors also thank Mizanur Rahman, Karolinska Institutet, for advice on the flow cytometry data analysis, and Dr. Olivier Chaloin for the synthesis of fMLP performed at the Institut de Biologie Mol?culaire et Cellulaire (Strasbourg, France).
Publisher Copyright:
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2019/9/1
Y1 - 2019/9/1
N2 - 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.
AB - 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.
KW - biodegradation
KW - cancer
KW - chemoattractants
KW - drug delivery
KW - graphene
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U2 - 10.1002/adfm.201901761
DO - 10.1002/adfm.201901761
M3 - Article
AN - SCOPUS:85073884629
SN - 1616-301X
VL - 29
JO - Advanced Functional Materials
JF - Advanced Functional Materials
IS - 39
M1 - 1901761
ER -