Graphene and Graphene Oxide-Based Nanocarriers for Targeted Delivery of Mitoxantrone in Cancer Therapy

Mitoxantrone (MTX) is limited by cardiotoxicity and MDR. At the same time, graphene oxide (GO) and nano-graphene oxide (NGO) offer ultrahigh surface area, strong π-π interactions with aromatic drugs, and versatile surface chemistry, making them superior to many conventional nanocarriers for high-capacity, stimuli-responsive MTX delivery. Conventional chemotherapy remains constrained by nonspecific biodistribution, dose-limiting toxicity, and the frequent emergence of multidrug resistance. This review surveys recent advances in GO- and NGO-based nanocarriers developed for targeted delivery of mitoxantrone. The platforms examined include hyaluronic acid-Pluronic functionalization for CD44-mediated targeting and P-glycoprotein inhibition, biomimetic coatings derived from mesenchymal stem cells or cancer-cell exosomes, magnetic graphene oxide systems designed for mitochondrial delivery, hybrid gold-graphene constructs, and multi-stimuli-responsive designs that respond to acidic pH, near-infrared light, or external magnetic fields. Combination strategies that integrate chemotherapy with photothermal therapy, nitric oxide release, or immunotherapy are also considered. Molecular dynamics simulations together with in vitro and limited in vivo studies indicate high drug-loading capacities (commonly reaching 40-45 wt% and higher in selected systems), stimulus-triggered release within acidic microenvironments, improved intracellular accumulation in resistant cell lines, and enhanced antitumor activity relative to free MTX in preclinical models, frequently accompanied by reduced systemic exposure. Nevertheless, long-term biocompatibility, immunogenicity, biodegradation and clearance pathways, batch-to-batch reproducibility, scalable manufacturing, and the complete absence of clinical data remain major translational barriers. Further progress will require safer, more biodegradable graphene derivatives and rigorous toxicological characterization before these platforms can advance toward clinical evaluation.