Human Omental Mature Adipocytes used as Paclitaxel Reservoir for Cell-Based Therapy in Ovarian Cancer.

Primary human omental adipocytes and ovarian cancer cells establish a bidirectional communication in which tumor driven lipolysis is induced in adipocytes and the resulting fatty acids are delivered to cancer cells within the tumor microenvironment. Despite meaningful improvement in the treatment of epithelial ovarian cancer, its efficacy is still limited by the hydrophobicity and the untargeted effects related to the standard regimen chemotherapeutics such as paclitaxel. Herein, we firstly use omental adipocytes as a reservoir for paclitaxel, named Living Paclitaxel Bullets and secondly benefit from the established dialogue between adipocytes and cancer cells to engineer a drug delivery process that target specifically cancer cells. Our results show that mature omental adipocytes can successfully uptake paclitaxel and deliver it to ovarian cancer cells in a transwell co-culture based in vitro model. In addition, the efficacy of this proof-of-concept has been demonstrated in vivo and induces a significant inhibition of tumor growth when applied to a xenograft tumor model. The use of mature adipocytes could be suitable for clinical prospection in a cell-based therapy system, due to their mature and differentiated state, to avoid risks related to uncontrolled cell de novo proliferation capacity after the delivery of the antineoplastic drug as observed with other cell types when employed as drug carriers. This article is protected by copyright. All rights reserved.