Abstract
Drug resistance, difficulty in specific targeting and self-renewal properties of cancer stem cells (CSCs) all contribute to cancer treatment failure and relapse. CSCs have been suggested as both the seeds of the primary cancer, and the roots of chemo- and radio-therapy resistance. The ability to precisely deliver drugs to target CSCs is an urgent need for cancer therapy, with nanotechnology-based drug delivery system being one of the most promising tools to achieve this in the clinic. Exosomes are cell-derived natural nanometric vesicles that are widely distributed in body fluids and involved in multiple disease processes, including tumorigenesis. Exosome-based nanometric vehicles have a number of advantages: they are non-toxic, non-immunogenic, and can be engineered to have robust delivery capacity and targeting specificity. This enables exosomes as a powerful nanocarrier to deliver anti-cancer drugs and genes for CSC targeting therapy. Here, we will introduce the current explorations of exosome-based delivery system in cancer therapy, with particular focus on several exosomal engineering approaches that have improved their efficiency and specificity for CSC targeting.
Highlights
Cancer remains one of the leading causes of death due to the late diagnosis, poor prognosis, and frequent occurrence of drug resistance and metastasis (Colak and Medema, 2014)
Dendritic cells (DCs) were engineered to express αv integrin-specific iRGD peptide and lysosome-associated membrane glycoprotein 2b (Lamp2b) fusion protein, allowing the engineered dendritic cells (DCs) to secret exosomes with the iRDG peptide on their surface. These engineered exosomes have dramatically increased drug delivery efficiency and anti-tumor effect on αv integrin-positive breast cancer cells in a mouse model (Tian et al, 2014)
Exosomes with the neuron-specific rabies viral glycoprotein (RVG) peptide can bind to the acetylcholine receptor on neuronal cells and selectively knockdown certain genes in neurons, microglia, and oligodendrocytes by specific delivery of small interfering RNA into those cells (Alvarez-Erviti et al, 2011). These results indicated that adapted exosomes can serve as a powerful tool for neural cancer treatment
Summary
Cancer remains one of the leading causes of death due to the late diagnosis, poor prognosis, and frequent occurrence of drug resistance and metastasis (Colak and Medema, 2014). These engineered exosomes have dramatically increased drug delivery efficiency and anti-tumor effect on αv integrin-positive breast cancer cells in a mouse model (Tian et al, 2014). The best exosome cancer therapy is to have chemotherapeutic drug-loaded exosomes targeting CSCs in vivo.
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