Exosome-Based Cancer Therapy: Implication for Targeting Cancer Stem Cells

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.

Targeted exosome‐encapsulated erastin induced ferroptosis in triple negative breast cancer cells

“…Biomimetic nanomaterials have been extensively studied as drug delivery vectors, such as exosomes . Exosomes are a type of micro vesicle secreted by cells, which can transfer internal substances to surrounding cells efficiently through rich adhesion proteins interacting with cell membrane . Based on the above, we selected HFL‐1 cells as the maternal cells for the source of exosomes, which were characterized by DLS and TEM; the results showed that the average particle size was 88.45 ± 19.53 nm, with uniform size and typical vesicular structure.…”

Emerging role of exosome signalling in maintaining cancer stem cell dynamic equilibrium

“…Besides anti‐cancer therapeutic drugs, exosomes can also deliver various tumour antigens. Thus, exosomes could present CSC‐specific antigens to T cells and activate T cells for anti‐CSC immunization . In addition, exosomes can be used as natural nanovesicles to deliver exogenous small RNAs, including siRNA and microRNAs, which target CSC‐specific signal pathways, such as Wnt, Notch, Hippo, and Hedgehog, etc.…”

Extracellular vesicles as emerging targets in cancer: Recent development from bench to bedside

“…The advantage in size enables better biodistribution and bioavailability of exosomes in the human body. Escape of lung clearance and permeability across the blood-brain barrier were reported for exosome-based drug carriers (200, 254). In addition, exosomes could achieve targeted delivery compared to synthetic nanoparticles.…”

“…Cancer cells secrete more EVs than normal cells (193, 194), and consequently, patients with cancer have higher levels of EVs compared to healthy individuals (195–200). With the increased level of EVs in circulation and the packaging of cancer-related molecules, these vesicles may serve as promising biomarkers for cancer diagnoses.…”