Cancer stem cells-emanated therapy resistance: Implications for liposomal drug delivery systems

It is verified that failure in cancer therapy by conventional chemotherapeutic agents arise from cancer heterogeneity. That, a small subpopulation of cancer cells known as "cancer stem cells" (CSCs) are shown to be responsible for deriving clonal heterogeneity/diversity in tumors, which render them resistant to conventional treatment regimes. So far, efficient targeted cancer therapy by nanotechnology-based drug delivery approaches is well established. Among various introduced nanocarriers, the non-toxic nature and biocompatibility of liposome make it highly desirable for human studies. In addition, liposomal nanocarriers can be used to protect entrapped therapeutic agents against chemical and biological degradation, improve solubility of the encapsulated drugs, provide sustained drug release, extend in vivo half-life, reduce side effects, improve drug pharmacokinetic and pharmacodynamic profiles, reduce drug dosage and administration frequency. Further, multifunctional liposomes can be envisioned that are simultaneously loaded with different theranostics and chemically-modified with different tumor-specific surface ligands for targeted therapy. Such versatile nanocarrier can influence the physicochemical characteristics, immunological mechanisms, and uptake mechanisms following systemic delivery. Other strategies to improve tumor-specific tropism include delivery systems involving immune cells or their modulators. Here, we describe mechanisms by which CSC can promote drug resistance to impair the efficacy of cancer therapies. Then, we summarize the implication of each of these mechanisms as potential therapeutics ways to overcome the therapeutically-resistant CSCs. Further, we discuss the status, therapeutic potential and prospect of different liposomal drug delivery systems in overcoming CSC drug resistance in the clinic.