Exosome Guided Nanoparticles as Therapeutic Anticancer Agents

Cancer is a complex disease and is very difficult to treat. Multidrug resistance, metastasis, low tumor specificity, and the absence of efficient targeting mechanisms are major challenges for anticancer drugs. Cancer is the leading cause of mortality worldwide. Metallic nanoparticles of silver and copper are studied for their anticancer activity. However, toxicity in healthy tissues associated with naïve metallic nanoparticles limits their therapeutic use in humans. One of the widely recognized shortcomings for applying naïve metallic nanoparticles in cancer therapy is the lack of effective strategies for targeted delivery. Exosomes are nanoscopic, low immunogenic, highly biocompatible, non-toxic, and are known for intercellular communication. Recently, exosomes emerged as novel carriers for anticancer therapeutics. We developed a method for targeting the therapeutic nanoparticles to cancer sites by exosomes that would significantly improve therapeutic efficiency. In this study, we investigated the role of wheat germ agglutinin functionalized nanoparticles in endocytosis for the self-assembly of nanoparticles in late endosomes during the biogenesis of exosomes in MCF10A cells and osteoblast cells. Our findings also showed the proof of concept of how functionalized nanoparticles bypass the lysosomal pathway and maintain the native metallic form of silver-copper nanoparticles in exosomes. The Exosomes containing silver-copper nanoparticles were isolated, characterized, and tested for their specificity and toxicity in cancer cells. Our results demonstrate that MCF10A derived exosomes loaded with cargo nanoparticles were specific and toxic to its homologous cancer cells, whereas the healthy and heterologous cancer cells did not show toxicity. In conclusion, this is the first study to show the self-assembly of nanoparticles in exosomes to target and deliver breast cancer therapeutics.