The exploitation of lysosomes in cancer therapy with graphene-based nanomaterials
2023
Authors:
Ristić, BiljanaBošnjak, Mihajlo
Misirkić Marjanović, Maja
Stevanović, Danijela
Janjetović, Kristina
Harhaji-Trajković, Ljubica
Document Type:
Article (Published version)
Metadata
Show full item recordAbstract:
Graphene-based nanomaterials (GNMs), including graphene, graphene oxide, reduced
graphene oxide, and graphene quantum dots, may have direct anticancer activity or be used as
nanocarriers for antitumor drugs. GNMs usually enter tumor cells by endocytosis and can accumu late in lysosomes. This accumulation prevents drugs bound to GNMs from reaching their targets,
suppressing their anticancer effects. A number of chemical modifications are made to GNMs to
facilitate the separation of anticancer drugs from GNMs at low lysosomal pH and to enable the
lysosomal escape of drugs. Lysosomal escape may be associated with oxidative stress, permeabi lization of the unstable membrane of cancer cell lysosomes, release of lysosomal enzymes into the
cytoplasm, and cell death. GNMs can prevent or stimulate tumor cell death by inducing protective
autophagy or suppressing autolysosomal degradation, respectively. Furthermore, because GNMs
prevent bound fluorescent agents from emitting light, their separation in lysosomes may enable
tumor cell identification and therapy monitoring. In this review, we explain how the characteristics
of the lysosomal microenvironment and the unique features of tumor cell lysosomes can be exploited
for GNM-based cancer therapy.
Keywords:
graphene-based nanomaterials; graphene-based drug delivery systems; lysosomes; cancer; endosomal/lysosomal escape; lysosomal cell deathSource:
Pharmaceutics, 2023, 15, 7, 1846-Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200110 (University of Belgrade, Faculty of Medicine) (RS-MESTD-inst-2020-200110)
DOI: 10.3390/pharmaceutics15071846
ISSN: 1999-4923
PubMed: 37514033