Manufacturing of exosome mimetic nanovesicles
Exosomes, the endogenous nanocarriers that can deliver biological information between cells, were recently introduced as a novel drug delivery system. However, mammalian cells release relatively low quantities of exosomes, and purification of exosomes is difficult.
We have developed bioinspired exosome-mimetic nanovesicles that deliver chemotherapeutics to the tumor tissue after systemic administration. The chemotherapeutics-loaded nanovesicles were produced by the breakdown of monocytes or macrophages using our unique centrifugation technology.
These cell-derived nanovesicles have similar characteristics with the exosomes but have 300-fold higher production yield. Furthermore, the nanovesicles have natural targeting ability of cells by maintaining the topology of plasma membrane proteins. in vitro
, chemotherapeutic drug-loaded nanovesicles induced TNF-R-stimulated endothelial cell death in a dose-dependent manner.
, experiments in mice showed that the chemotherapeutic drug-loaded nanovesicles traffic to tumor tissue and reduce tumor growth without the adverse effects observed with equipotent free drug. Furthermore, compared with chemotherapeutic loaded exosomes, chemotherapeutic loaded nanovesicles showed similar in vivo
antitumor activity. However, chemotherapeutic loaded liposomes that did not carry targeting proteins were inefficient in reducing tumor growth.
Importantly, removal of the plasma membrane proteins by trypsinization eliminated the therapeutic effects of the nanovesicles both in vitro
and in vivo
It is clear that the bioengineered nanovesicles can serve as novel exosome-mimetics to effectively deliver chemotherapeutics to treat malignant tumors.
Now we establish the encapsulation and stabilization process of some of cytotoxic agents to exosome-mimetic nanovesicles. Once the process is validated, we will carried out efficacy and toxicity study for the final drug formulations.