RNAi-Loaded Exosomes for the Management of Breast Cancer: Emerging Paradigms in Precision Therapy

Breast cancer is a heterogeneous disease and is characterized by desmoplastic tumors. Conventional nanocarriers are unable to accumulate in the tumor microenvironment owing to their inability to extravasate through tumor vessels and the high density of the desmoplastic breast tumor. In addition, the exogenous nature of nanocarriers makes them susceptible to recognition by the reticuloendothelial system and therefore leads to short systemic half-life. Exosomes, also known as the body's natural nanocarriers, have an inherent ability to carry nucleic acids. Due to their endogenous nature, they can bypass the macrophages and thus, show prolonged systemic half-life. Exosomes isolated from sources such as macrophages, neutrophils, and mesenchymal stem cells have demonstrated the ability to penetrate and accumulate in breast tumors. Thus, in the present review article, we have highlighted advantages and challenges associated with the delivery of RNAi-loaded exosomes for the precision therapy of breast cancer. Additionally, it reviews various oncogenic targets and the ability of RNAi-loaded exosomes to modulate them. We have also mentioned the common bottlenecks and challenges faced by formulation scientists in the clinical translation of RNAi-loaded exosomes.