Latest developments in advanced exosome engineering for optimized site-specific drug delivery by modulating exosome functionalities in breast cancer

Breast cancer (BC), the second most common cancer worldwide, is frequently treated with chemotherapeutic agents as part of neoadjuvant therapies. However, the major drawback of chemotherapy comes at the cost of nonspecific drug targets. This could be minimized by developing site-specific targeted therapy. Exosomes, nano-sized naturally secreted extracellular vesicles, are being investigated as potential candidates for a targeted drug delivery platform. The ease of surface engineering and drug-loading capabilities make exosomes an excellent carrier for targeted drug delivery. Since Doxorubicin was used for exosome-mediated drug delivery in BC, numerous drug loading and packaging strategies were reported towards targeted therapy of BC. In this article, we have discussed the recent developments in exosome engineering strategies and approaches for exosome modifications to target BC cells. Exosome surface modifications could be achieved by biological, immunological, and chemical methods. In addition to site specific targeting, the use of exosomes as drug carriers have also been discussed. We have tried to find out the reason behind unsuccessful clinical trials worldwide, despite of tremendous progress over a decade, and why so few made it to the bedside and those only as biomarkers not as therapeutic interventions. Substantial clinical trials, further refinement of drug loading and targeting strategies are warranted for clinical success of exosomes as nano-carriers and drug delivery agents.