Nanomaterials Targeting Cancer Stem Cells to Overcome Drug Resistance and Tumor Recurrence

DIVYA VISHAMBHAR KUMBHAKAR¹Lucky Thakkar²Chetana Akhand³Shehna Sharaf¹Geeta K Vemuganti^1*

• ¹School of Medical Sciences, University of Hyderabad, Telengana, Andhra Pradesh, India
• ²Department of Applied Genetics, Karnatak University, Dharwad, Karnataka, India
• ³Environmental Biotechnology and Genomics Division, National Environmental Engineering Research Institute (CSIR), Nagpur, Maharashtra, India

A cancer stem cell (CSC) is an immortal cell that is capable of self -renewal, continuous proliferation, differentiation into various cancer cell lineages, metastatic dissemination, tumorigenesis, maintaining tumor heterogeneity and resistance to conventional treatments. Targeted therapies have made huge advances in the past few years, but resistance has still been a major roadblock to their success, in addition to their life-threatening side effects. Progressive treatments are now available, including immunotherapies, CRISPR-Cas 9, sonodynamic therapy, chemodynamic therapy, antibody-drug nanoconjugates, cell-based therapies, gene therapy, and ferroptosis-based therapy, which have replaced surgery, chemotherapy, and radiotherapy for cancer treatment. The challenge is to develop targeted treatment strategies that are effective in eradicating CSCs, as they are resistant to anti-cancer drugs, causing treatment failure, relapse and recurrence of cancer. An overview of the fundamental characteristics of CSCs, drug resistance, tumor recurrence, and signaling pathways as well as biomarkers associated with their metastatic potential of CSC, is elucidated in this review. The regulatory frameworks for manufacturing and conducting clinical trials on cancer therapy are explicated. Furthermore, we have summarized a variety of promising nanocarriers (NCs) that have been used directly and/or synergistic therapies coupled with therapeutic drug of choice for detection, targeting and imaging of CSCs, to surmount therapeutic resistance, stemness-related signaling pathways and eradication of CSCs, hence alleviating the limitation of conventional therapies. Nanoparticle-mediated ablation therapies (NMAT) are also being argued as a method for burning or freezing cancer cells without undergoing open surgery. Additionally, we discussed about the recent clinical trials testing exosomes, CRISPR/Cas9, and nanodrugs, which have already received approval for several new technologies, while others are still in the early stages of testing. The objective of this review is to elucidate the advantages of nanocarriers in conquering cancer drug resistance, and to discuss the most recent developments in this field.