Targeting Cancer Stemness Using Nanotechnology in a Holistic Approach: A Narrative Review

Increasing evidence shows that a very small population of cancer stem cells (CSCs) is responsible for cancer recurrence, drug resistance, and metastasis. CSCs usually reside in hypoxic tumor regions and are characterized by high tumorigenicity. Their inaccessible nature allows them to avoid the effects of conventional treatments such as chemotherapy, radiotherapy, and surgery. In addition, conventional chemo- and radiotherapy is potentially toxic and could help CSCs to spread and survive. New therapeutic targets against CSCs are sought, including different signaling pathways and distinct cell surface markers. Recent advances in nanotechnology have provided hope for the development of new therapeutic avenues to eradicate CSCs. In this review, we present newly discovered nanoparticles that can be co-loaded with an apoptosis-inducing agent or differentiation-inducing agent, with high stability, cellular penetration, and drug release. We also summarize the molecular characteristics of CSCs and the signaling pathways responsible for their survival and maintenance. Controlled drug release targeting CSCs aims to reduce stemness-related drug resistance, suppress tumor growth, and prevent tumor relapse and metastases.