title: Can nanomedicines kill cancer stem cells?
abstract: Most tumors are heterogeneous and many cancers contain small population of highly tumorigenic and intrinsically drug resistant cancer stem cells (CSCs). Like normal stem cell, CSCs have the ability to self-renew and differentiate to other tumor cell types. They are believed to be a source for drug resistance, tumor recurrence and metastasis. CSCs often overexpress drug efflux transporters, spend most of their time in non-dividing G0 cell cycle state, and therefore, can escape the conventional chemotherapies. Thus, targeting CSCs is essential for developing novel therapies to prevent cancer relapse and emerging of drug resistance. Nanocarrier-based therapeutic agents (nanomedicines) have been used to achieve longer circulation times, better stability and bioavailability over current therapeutics. Recently, some groups have successfully applied nanomedicines to target CSCs to eliminate the tumor and prevent its recurrence. These approaches include 1) delivery of therapeutic agents (small molecules, siRNA, antibodies) that affect embryonic signaling pathways implicated in self-renewal and differentiation in CSCs, 2) inhibiting drug efflux transporters in an attempt to sensitize CSCs to therapy, 3) targeting metabolism in CSCs through nanoformulated chemicals and field-responsive magnetic nanoparticles and carbon nanotubes, and 4) disruption of multiple pathways in drug resistant cells using combination of chemotherapeutic drugs with amphiphilic Pluronic block copolymers. Despite clear progress of these studies the challenges of targeting CSCs by nanomedicines still exist and leave plenty of room for improvement and development. This review summarizes biological processes that are related to CSCs, overviews the current state of anti-CSCs therapies, and discusses state-of-the-art nanomedicine approaches developed to kill CSCs.
authors.affiliation: Center for Nanotechnology in Drug Delivery and Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7362, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.forename: Daria Y
authors.initials: DY
authors.lastname: Alakhova
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Kabanov
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D001692:Biological Transport; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008954:Models, Biological; D050997:Nanomedicine / Q000379:methods* / Q000639:trends; D049329:Nanostructures / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010316:Particle Size
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers
keywords: Cancer; Cancer stem cells; Drug delivery; Nanomedicine; Polymer therapeutics