University of Science and Technology of China  South China University of Technology 中文|English

Cancer Stem Cell Therapy

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The discovery of cancer stem cells (CSCs) has changed the view of cancer therapy. CSCs are thought to be responsible for the origin, metastasis and recurrence of cancers. Increasing evidence supports the idea that, instead of merely targeting the bulk non-CSCs, successful cancer curation may require both undifferentiated CSCs and differentiated non-CSCs to be efficiently eliminated. To this end, several promising strategies have been developed for CSC-targeted therapy. These include direct inhibition of CSCs by blocking their vital self-renewal signaling, induction of CSCs to differentiate into bulk tumor cells that are susceptible to standard therapies, and screening and identification of drug candidates that are able to specifically kill CSCs. The standard chemotherapy towards CSCs using conventional chemotherapeutic agents is unfortunately ineffective as it leads to the enrichment of CSCs and ends up with tumor relapse. With novel well-designed drug delivery systems, conventional chemotherapeutic agents still hold promise for cancer stem cell therapy.

1. We previously developed PPC-Hyd-DOX-DA and demonstrated that the nanoparticle can respond to both extracellular and intracellular pH environments, and hence simultaneously augment cellular uptake and promote acid-triggered intracellular drug release. With dual pH sensitivities, the nanoparticle has shown enhanced inhibition of the progression of drug-resistant cancer stem cells. 

2. We further reported that DOX-Hyd@AuNPs nanoparticles can deliver more Doxorubicin (DOX) into the breast CSCs by overcoming the intrinsic resistance through the evasion of the efflux of P-gp.

3. We also developed several effective strategies for cancer stem cell therapy, including targeting CSCs-related metabolism, combination treatment through simultaneous delivery of two or more drugs with the nanoparticles.

We are continuing to explore novel strategies by optimizing drug delivery systems, screening new targets of CSCs, and developing more advanced CSC-targeting approaches for enhanced cancer therapies.