Nanoparticles for Targeted Drug Delivery to Cancer Stem Cells: A Review of Recent Advances

Abstract

Cancer stem cells (CSCs) are a subpopulation of cells that can initiate, self-renew, and sustain tumor growth. CSCs are responsible for tumor metastasis, recurrence, and drug resistance in cancer therapy. CSCs reside within a niche maintained by multiple unique factors in the microenvironment. These factors include hypoxia, excessive levels of angiogenesis, a change of mitochondrial activity from aerobic aspiration to aerobic glycolysis, an upregulated expression of CSC biomarkers and stem cell signaling, and an elevated synthesis of the cytochromes P450 family of enzymes responsible for drug clearance. Antibodies and ligands targeting the unique factors that maintain the niche are utilized for the delivery of anticancer therapeutics to CSCs. In this regard, nanomaterials, specifically nanoparticles (NPs), are extremely useful as carriers for the delivery of anticancer agents to CSCs. This review covers the biology of CSCs and advances in the design and synthesis of NPs as a carrier in targeting cancer drugs to the CSC subpopulation of cancer cells. This review includes the development of synthetic and natural polymeric NPs, lipid NPs, inorganic NPs, self-assembling protein NPs, antibody-drug conjugates, and extracellular nanovesicles for CSC targeting.

Nano-Based Approved Pharmaceuticals for Cancer Treatment: Present and Future Challenges

“…Combining CSC marker targeting and drugs loaded onto nanomaterials can be effective against CSCs, increasing specificity and selectivity. Novel tools that aim to detect, characterize, and eliminate CSCs with enhanced efficacy are ongoing [ 139 , 140 ]. A considerable number of different nanoparticles have been evaluated, from anti-CSC ADCs [ 141 ], to nanoparticle-based RNAi [ 142 ], to nano-based thermotherapy [ 143 ].…”

The Promise of Nanotechnology in Personalized Medicine

“…Due to their high plasticity after radiotherapy and chemotherapy, cancer stem cells can adopt a different phenotype that allows them to survive and give rise to a new subpopulation of tumor cells [ 144 , 145 ]. The identification of specific TME and cancer stem cells biomarkers is of particular importance for new personalized anticancer therapies [ 146 , 147 ]. Within this framework, Gaio and co-workers designed hyaluronic acid-coated polymeric nanoparticles for the delivery of docetaxel and the photosensitizer meso-tetraphenyl chlorine di-sulfonate targeting breast cancer stem cells over-expressing the CD44 glycoprotein, combining within a single nano construct chemotherapy and photodynamic therapy [ 148 ].…”

Targeting cancer stem cells with polymer nanoparticles for gastrointestinal cancer treatment

“…Current research shows the main signaling pathways related to GI malignancies: Notch signaling pathway, WNT/-beta-catenin pathway, Hedgehog (Hh) pathway, etc. These pathways play an important role in the occurrence, growth, differentiation, metastasis, invasion, and other processes of CSCs [ 32 ]. Although different signal pathways have different roles, they are also inextricably linked.…”