The Dark Side of Nanomedicines: Unintended Consequences in Cancer Therapy

Nanomedicine has emerged as a powerful strategy in cancer therapy, enabling targeted drug delivery, enhanced imaging, and improved therapeutic indices through nanoscale engineering. Despite these advantages, increasing evidence highlights unintended biological effects associated with nanoparticle exposure that raise important safety concerns. This review critically examines the adverse consequences of nanomedicine in oncology, with emphasis on mechanistic pathways underlying nanotoxicity. Key processes discussed include oxidative stress generation, mitochondrial dysfunction, lysosomal membrane permeabilization, immune activation, genotoxicity, and dysregulation of redox-sensitive signalling pathways such as NF-κB and MAPKs. The influence of nanoparticle physicochemical properties—composition, size, surface chemistry, and biodistribution—on toxicological outcomes is also evaluated. By integrating findings from in vitro and in vivo studies, this review highlights the dualistic nature of nanomedicine, where therapeutic efficacy may coexist with off-target toxicity and long-term biological risks. Understanding these mechanisms is critical for the rational design of safer nanomaterials and for advancing the responsible clinical translation of nanomedicine-based cancer therapies.