Title : Nanomaterials for targeting stem cells
A major contributing factor to mortality in cancer patients is relapse after therapy. Cancer recurrence and resistance is related to the existence of a very small population of cancer stem cells (CSCs) in the tumor tissue with high expression of ATP-binding transporter proteins associated with drug resistance. After therapy, the bulk of tumor shrinks to <1% of its initial volume and the tumor tissue becomes enriched with CSCs that are highly resistant. Further, as much as 40% of the volume of solid tumors is occupied by tumor-associated macrophages (TAMs), specifically immunosuppressive M2-macrophages, which play a central role in cancer progression. One approach to overcome carrier-mediated drug resistance in CSCs is to use nanoparticles (NPs) for intracellular delivery. Unlike drug molecules in which their uptake is affected by up-regulation of ABC transporter proteins, NPs utilize endocytosis for transcellular cell uptake. Although the enhanced permeation and retention of NPs in the tumor tissue are extensively investigated, little is known about the role of TAMs on uptake and toxicity of drug-loaded NPs toward CSC sub-population of cancer cells. I will present results related to the effect of macrophages on toxicity of drug conjugated NPs toward CSCs within a novel three-dimensional CSC-enriching culture system.
Audience take away:
- Audience will learn about synthesis and drug conjugation to NPs
- Audience will learn about the effect of chemotherapeutic agents on cancer stem cells
- Audience will learn about the interaction and signaling between cancer stem cells and tissue macrophages
- Audience will learn about the effect of nanoparticles on drug delivery to stem cells