Exosomes in development, metastasis and drug resistance of breast cancer.
Bottom Line: Exosome-delivered nucleic acid and proteins partly facilitate the tumorigenesis, metastasis and resistance of breast cancer.However, exosomes are effective tools for transportation of anti-cancer drugs with lower immunogenicity and toxicity.This is a promising way to establish a drug delivery system.
Affiliation: The First Clinical School of Nanjing Medical University, Nanjing, China.Show MeSH
Related in: MedlinePlus
Mentions: Exosomes that are endogenous nano-sized membrane vesicles can be used to carry drugs with low immunogenicity and toxicity.66 Exosomes after modification to target breast cancer cells could be used to deliver doxorubicin (dox).67 Purified exosomes loaded with dox via electroporation, produced by mouse immature dendritic cells to reduce immunogenicity and toxicity, are highly efficient at targeting and dox delivery, leading to significant inhibition of breast cancer without obvious toxicity. As reported, exosomes derived from epigallocatechin gallate are able to inhibit infiltration of tumor-associated macrophage and polarization of M2 macrophages, thereby suppressing breast cancer growth.68 Exosomes have the potential to worsen the tumor microenvironment for cancer growth. Immunity escape is an important characteristic of breast cancer. Curcumin-pretreated exo-BCa could reverse immune suppression of NK cell activation, which may account for anti-cancer properties of curcumin. In other words, exosomes are able to transmit anti-tumor substances to recover the surveillance of immune system. Exosomes released by adenoviral vector (AdVHER2)-transfected dendritic cells proved capable of inducing HER2-specific cytotoxic T lymophocyte responses and protective immunity against trastuzumab-resistant breast cancer in vitro.69 This novel HER2-TEXO vaccine may offer a better therapeutic choice for HER2-positive breast cancer patients, especially trastuzumab-resistant patients. Nevertheless, there are also some unsolved problems in the clinical application of exosomes. The acquisition of plenty of exosomes is inconvenient owing to the low number of exosomes. Thus, researchers must seek better methods to produce plenty of exosomes without great cost. The way in which exosomes should enter the body is also controversial. Intravenous injection is convenient but the exosomes should be targeted to breast cancer cells, which is a challenge for exosome design. Local injection avoids the problem of targeted delivery design, but it faces new problems. Whether locally injected exosomes are absorbed effectively and cover all breast cancer cells remains unresolved. Figure4 presents a summary diagram of exosomes in breast cancer therapeutics.
Affiliation: The First Clinical School of Nanjing Medical University, Nanjing, China.