Rucaparib-bearing NanoGhosts as a potential tumor-suppressing agent

According to the International Agency for Research on Cancer, 19.3 million new cancer cases were seen in the world for 2020, including 495,773 cases of pancreas cancer, which has one of the highest mortality rates (94%)[1]. The ultimate goal in cancer therapy nowadays is a ‘magic bullet’ that provides a versatile drug-delivery vehicle for site-specific targeting of multiple cancers implemented in a clinically relevant and non-toxic design[2]. This approach allows to reject traditional therapeutics’ disadvantages and has already been attempted in clinical trials. The design of the NanoGhosts (NGs) drug delivery platform is based upon nanovesicles from the cytoplasmatic membrane of mesenchymal stem cells (MSCs), which are known by tumor-targeting abilities[3]. Lipophilic rucaparib, the poly (ADP-ribose) polymerase inhibitor, has high potential in cancer therapy and has already received global approval for cancer treatment[4]. Despite the efficient inhibition of cell growth, the application of rucaparib is still limited by its high toxicity and side effects such as neutropenia, fever, thrombocytopenia, etc[5]. Here we develop the targeted delivery system of rucaparib through its incorporation in NanoGhosts for the selective therapy of cancer.

NGs were fabricated via high-pressure extrusion of isolated MSCs membranes and had mode size ~180 nm and narrow size distribution. Pancreas cancer cells were used as an in vitro model. The targeting ability of NGs was shown on pancreas cancer cells in comparison with normal somatic cells. Rucaparib was encapsulated into NGs via the modified coincubation method with high encapsulation efficiency. Rucaparib-NGs demonstrated a concentration-dependent cytotoxicity inhibition effect on pancreas cancer cells at different exposure times. Even after 1 hour of exposure (active NGs uptake), significant inhibition of cell growth was observed.

The current NGs-based delivery system of rucaparib has strong potential for further application in cancer treatment and will be investigated on in vivo cancer models.

[1] H.Sung, et al. Global Cancer Statistics 2020, Vol. 71, 2021, pp. 209–249.

[2] T.M.Fahmy, et al. Mater. Today 2005, 8, 18.

[3] A.Hmadcha, et al. Front. Bioeng. Biotechnol. 2020, 8, 43.

[4] Y.Y.Syed, Drugs 2017, 77, 585.

[5] Y.Drew, et al. Br. J. Cancer 2016 1147 2016, 114, 723.