# The Exploitation of Lysosomes in Cancer Therapy with Graphene-Based Nanomaterials
## 1 Introduction  
Despite significant efforts and resources invested in cancer research, cancer is still the second leading cause of death [1]. The main problems in cancer therapy are drug resistance and the harmful side effects of drug therapy. Uncontrolled cell proliferation and a high mutation rate enable a rapid selection of drug-resistant cell clones. Chemotherapeutic agents often interfere with signaling pathways found in both malignant and healthy cells, leading to undesirable of-target effects. To reduce side effects and increase the effectiveness of cancer therapy, scientists are looking for specific characteristics of cancer cells that can be targeted [2]. Lysosomes are the membrane-enclosed digestive organelles, with a putative role in tumor growth and metastasis. Cancer cells have a large number of lysosomes, while their lysosomes have increased enzyme content and unstable membranes. These characteristics, along with the unique features of the lysosomal compartment (low pH and presence of acid hydrolases), can be effectively exploited for cancer therapy [3].  
As highly biocompatible materials with unique physicochemical properties, graphene-based nanomaterials (GNMs) are widely studied for the development of innovative anticancer therapeutics. GNMs exhibit direct anti-cancer effects by inducing tumor cell death or inhibiting angiogenesis. Their selectivity against cancer cells can be improved by functionalization with targeting moieties that bind to specific receptors on tumor cells. Additionally,owing to their extensive surface area, GNMs can serve as carriers for anticancer drugs, forming graphene-based drug delivery systems (DDSs) that enhance the targeting and delivery of drugs to tumor cells. The optical properties of GNMs can be harnessed for both photothermal therapy (PTT) and real-time monitoring of cancer treatment [4; 5].  
GNMs are predominantly internalized in tumor cells via endocytosis, and in cases where they fail to escape from endosomes, they ultimately enter lysosomes [6; 7; 8]. Their lysosomal accumulation may suppress the activity of lysosomal enzymes [9], leading to a reduction in autophagic degradation, which typically serves as a protective mechanism [9; 10; 11], thereby contributing to tumor cell death. The sequestration of graphene-based DDSs in the lysosomal lumen prevents drugs from reaching their target site. Various functionalizations of GNMs have been developed to enable lysosomal drug escape [12; 13; 14; 15]. Finally, GNMs can induce lysosomal membrane permeabilization (LMP) [15] and lysosomal cell death (LCD) [16; 17]. This could be a promising strategy for cancer therapy due to the inherent instability of lysosomes in cancer cells.  
While numerous studies in the literature have demonstrated the critical role of lysosomes in the anticancer effects of GNMs, there has been no summary review. The purpose of this article is to recapitulate the studies that have demonstrated positive and negative involvement of lysosomes in the anticancer effects of GNMs, and to explain the underlying mechanisms. To identify relevant articles, we conducted a comprehensive search of the PubMed database using the search terms \"graphene,\" \"lysosomes,\" and \"cancer.\"