Functionalized Graphene Platforms for Anticancer Drug Delivery

Figures & data

Figure 1 Graphite and different allotropic forms of carbon.

Notes: Used with permission of Future Medicine Ltd from Tonelli FM, Goulart VA, Gomes KN, et al. Graphene-based nanomaterials: biological and medical applications and toxicity. Nanomedicine. 2015;10:2423–2450; permission conveyed through Copyright Clearance Center, Inc. ⁴⁰

Figure 2 Structure of graphene and its oxidized derivatives.

Notes: Reproduced with permission from Priyadarsini S, Mohanty S, Mukherjee S, Basu S, Mishra M. Graphene and graphene oxide as nanomaterials for medicine and biology application. Journal of Nanostructure in Chemistry. 2018;8:123–137.⁴¹ Copyright © 2018, The Authors. Creative Commons CC BY (https://creativecommons.org/licenses/by/4.0/legalcode).

Figure 3 The controlled functionalization of nanographene sheets through nitrene [2+1] cycloaddition reaction at ambient conditions.

Notes: The nucleophilic substitution of chlorine atoms in triazine groups with different polymers and (macro)molecules results in new platforms with defined structures. Reproduced with permission from Gholami MF, Lauster D, Ludwig K, et al. Functionalized graphene as extracellular matrix mimics: toward well‐defined 2D nanomaterials for multivalent virus interactions. Adv Funct Mater. 2017;27:1606477.¹¹² Copyright 2017, Advanced Functional Materials.

Figure 4 GO with PEI coverage coloaded with cisplatin and topotecan for mitochondria targeting of cancer cells.

Notes: Reproduced with permission from Mallick A, Nandi A, Basu S. Polyethylenimine coated graphene oxide nanoparticles for targeting mitochondria in cancer cells. ACS Applied Bio Mater. 2018;2:14–19.¹¹⁶ Copyright 2019, American Chemical Society.

Figure 5 Schematic representation of the synthesis and cellular uptake of GO nanoparticle/chitosan hybrids as drug delivery system.

Notes: This system was sensitive to changes in pH through which intracellular DOX delivery was controlled. Reproduced with permission from Zhao X, Wei Z, Zhao Z, et al. Design and development of graphene oxide nanoparticle/chitosan hybrids showing pH-sensitive surface charge-reversible ability for efficient intracellular doxorubicin delivery. ACS Appl Mater Interfaces. 2018;10:6608–6617.¹⁵⁰ Copyright 2018, American Chemical Society.

Figure 6 (A) The chemical structure of the polyglycerol-covered nanographene with the mitochondria-targeting ligands and charge conversional functional groups. (B) Multifunctional drug delivery system accumulates in mitochondria by targeting ligands and photothermal properties under NIR laser irradiation result in drug release and good therapeutic efficiency.

Notes: Reproduced with permission from Tu Z, Qiao H, Yan Y, et al. Directed Graphene‐based Nanoplatforms for hyperthermia: Overcoming multiple drug resistance. Angewandte Chemie. 2018;130:11368–11372.¹⁴ Copyright © 2018 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim.

Figure 7 Functionalized rGO with thiol-maleimide containing catechol (dopa-MAL) as a targeted drug delivery system for DOX to destroy human breast adenocarcinoma cancer cells (MDA-MB-231).

Notes: Reproduced with permission from Oz Y, Barras A, Sanyal R, Boukherroub R, Szunerits S, Sanyal A. Functionalization of reduced graphene oxide via thiol–maleimide “click” chemistry: facile fabrication of targeted drug delivery vehicles. ACS Appl Mater Interfaces. 2017;9:34194–34203.¹⁷⁰ Copyright © 2017, American Chemical Society.

Figure 8 Synthesis of folic acid-functionalized PEGylated GO (GO-PEG-Fol), with small size and narrow size distribution (∼30 ± 5 nm), and the ability of efficient converting NIR light into heat.

Notes: GO-PEG-Fol is able to actively target MCF7 and MDA-MB-231 cells. Reprinted from Materials Science and Engineering: C, Vol 107, Mauro N, Scialabba C, Agnello S, Cavallaro G, Giammona G, Folic acid-functionalized graphene oxide nanosheets via plasma etching as a platform to combine NIR anticancer phototherapy and targeted drug delivery, Pages No.,110201 Copyright (2020), with permission from Elsevier.¹⁷³

Figure 9 (A) Schematic representation of the synthesis of the polyglycerol amine functionalized graphene sheets (GA), polyglycerol sulfate-functionalized graphene sheets (GS) and conjugation of pH-sensitive dye to the GA and GS (GAD, GSD). Information regarding the synthesis these graphene platforms can be found in ref.¹⁶⁶ In vitro release profile of DOX from the GAD (B) and GSD (C) at 37 °C in various media.

Notes: Reproduced with permission of Royal Society of Chemistry from Tu Z, Wycisk V, Cheng C, Chen W, Adeli M, Haag R. Functionalized graphene sheets for intracellular controlled releaseof therapeutic agents. Nanoscale. 2017;9:18931–18939.¹³¹ Copyright 2017, Advanced Functional Materials; permission conveyed through Copyright Clearance Center,Inc.

Figure 10 Schematic presentation of the functionalization of QDs by poly(l-lactide)-PEG and their application for cell imaging.

Notes: A strong signal for the functionalized QDs can be seen in HeLa cells. Low toxicity has also been observed for this material. Gene probes were loaded onto the surface of functionalized QDs with π-π interaction. The uptake of probes by HeLa cells can be controlled by the intrinsic photoluminescence of QDs, while the fluorescence of the gene probe applied to identify the target is used to monitor gene regulation. Probe 1 is an inhibitor probe of miRNA-21 and probe 2 is survivin antisense oligodeoxynucleotide. Reproduced with permission from Dong H, Dai W, Ju H, et al. Multifunctional poly (l-lactide)–polyethylene glycol-grafted graphene quantum dots for intracellular microRNA imaging and combined specific-gene-targeting agents delivery for improved therapeutics. ACS Appl Mater Interfaces. 2015;7:11015–11023.²⁰⁸ Copyright © 2015, American Chemical Society.

Figure 11 Schematic representation of the synthesis of DOX-BSA-rGO as a light sensitive drug delivery system for chemo-photothermal therapy.

Notes: Albumin is attached onto the surface of exfoliated GO and DOX is loaded onto the surface of BSA-rGO nanosheets. This system has enhanced therapeutic efficacy of DOX drug due to the synergic effect of chemotherapy and photothermal therapy. Reproduced with permission from Cheon YA, Bae JH, Chung BG. Reduced graphene oxide nanosheet for chemo-photothermal therapy. Langmuir. 2016;32:2731–2736.²¹⁵ Copyright © 2016, American Chemical Society.

Figure 12 Schematic presentation of fabrication of GO-based gene delivery system through covalent attachment of LMW BPEI to this platform.

Notes: Conjugation of BPEI to GO enhances the photoluminescence properties of GO and improves the cellular uptake and transfection efficiency of the system. Therefore, BPEI-GO can be applied as bioimaging reagent and non-viral gene delivery vector simultaneously. Reproduced with permission from Kim H, Namgung R, Singha K, Oh IK, Kim WJ. Graphene oxide–polyethylenimine nanoconstruct as a gene delivery vector and bioimaging tool. Bioconjug Chem. 2011;22:2558–2567.²⁵⁰ Copyright © 2011, American Chemical Society.

Tonelli FM, Goulart VA, Gomes KN, et al. Graphene-based nanomaterials: biological and medical applications and toxicity. Nanomedicine. 2015;10:2423–2450. doi:10.2217/nnm.15.65

 PubMed Web of Science ®Google Scholar

Priyadarsini S, Mohanty S, Mukherjee S, Basu S, Mishra M. Graphene and graphene oxide as nanomaterials for medicine and biology application. J Nanostructure Chem. 2018;8:123–137. doi:10.1007/s40097-018-0265-6

 Web of Science ®Google Scholar

Gholami MF, Lauster D, Ludwig K, et al. Functionalized graphene as extracellular matrix mimics: toward well‐defined 2D nanomaterials for multivalent virus interactions. Adv Funct Mater. 2017;27:1606477. doi:10.1002/adfm.201606477

 Google Scholar

Mallick A, Nandi A, Basu S. Polyethylenimine coated graphene oxide nanoparticles for targeting mitochondria in cancer cells. ACS Applied Bio Mater. 2018;2:14–19. doi:10.1021/acsabm.8b00519

 PubMedGoogle Scholar

Zhao X, Wei Z, Zhao Z, et al. Design and development of graphene oxide nanoparticle/chitosan hybrids showing pH-sensitive surface charge-reversible ability for efficient intracellular doxorubicin delivery. ACS Appl Mater Interfaces. 2018;10:6608–6617. doi:10.1021/acsami.7b16910

 PubMed Web of Science ®Google Scholar

Tu Z, Qiao H, Yan Y, et al. Directed graphene‐based nanoplatforms for hyperthermia: overcoming multiple drug resistance. Angew Chem. 2018;130:11368–11372. doi:10.1002/ange.201804291

 Google Scholar

Oz Y, Barras A, Sanyal R, Boukherroub R, Szunerits S, Sanyal A. Functionalization of reduced graphene oxide via thiol–maleimide “click” chemistry: facile fabrication of targeted drug delivery vehicles. ACS Appl Mater Interfaces. 2017;9:34194–34203. doi:10.1021/acsami.7b08433

 PubMed Web of Science ®Google Scholar

Mauro N, Scialabba C, Agnello S, Cavallaro G, Giammona G. Folic acid-functionalized graphene oxide nanosheets via plasma etching as a platform to combine NIR anticancer phototherapy and targeted drug delivery. Mater Sci Eng C. 2020;107:110201. doi:10.1016/j.msec.2019.110201

 PubMed Web of Science ®Google Scholar

Tu Z, Achazi K, Schulz A, et al. Combination of surface charge and size controls the cellular uptake of functionalized graphene sheets. Adv Funct Mater. 2017;27:1701837. doi:10.1002/adfm.201701837

 Google Scholar

Tu Z, Wycisk V, Cheng C, Chen W, Adeli M, Haag R. Functionalized graphene sheets for intracellular controlled release of therapeutic agents. Nanoscale. 2017;9:18931–18939. doi:10.1039/C7NR06588D

 PubMedGoogle Scholar

Dong H, Dai W, Ju H, et al. Multifunctional poly (l-lactide)–polyethylene glycol-grafted graphene quantum dots for intracellular microRNA imaging and combined specific-gene-targeting agents delivery for improved therapeutics. ACS Appl Mater Interfaces. 2015;7:11015–11023. doi:10.1021/acsami.5b02803

 PubMed Web of Science ®Google Scholar

Cheon YA, Bae JH, Chung BG. Reduced graphene oxide nanosheet for chemo-photothermal therapy. Langmuir. 2016;32:2731–2736. doi:10.1021/acs.langmuir.6b00315

 PubMed Web of Science ®Google Scholar

Kim H, Namgung R, Singha K, Oh I-K, Kim WJ. Graphene oxide–polyethylenimine nanoconstruct as a gene delivery vector and bioimaging tool. Bioconjug Chem. 2011;22:2558–2567. doi:10.1021/bc200397j

 PubMed Web of Science ®Google Scholar