Femtosecond laser pulse assisted photoporation for drug delivery in Chronic myelogenous leukemia cells

Abstract

Chronic myelogenous leukemia (CML) is a myeloproliferative disorder occurs in the pluripotent hematopoietic stem cell. Currently, first-generation tyrosine kinase inhibitor (TKI) imatinib is the mainstay for the treatment of CML. Second generation TKI's like ponatinib, dasatinib, nilotinib, and bafetinib were treated against resistant CML. However, several CML patients develop resistance towards all existing inhibitors. Curcumin (Curcuma longa) a plant-derived natural compound is an effective bioactive component against various cancers including CML. Many studies have shown that curcumin induces time- and dose-dependent apoptosis in CML cells by regulating various downstream molecular regulators. Despite curcumin's selective cytotoxicity towards cancer cells, it has very poor bioavailability both in in-vitro and in-vivo conditions. In this present study, we have used femtosecond laser (fs-laser) pulses to ablate the cell membrane and standardized the conditions required for creating a cell membrane pores with less lethality. Following fs-laser pulse irradiation, K562 cells were incubated along with curcumin 30 μM for 0 h, 6 h,12 h and 24 h. Interestingly irradiated cells have shown higher sensitivity towards curcumin than non-irradiated cells. Immunoblotting studies showed higher induction levels of cleaved caspase 3 and 9 in irradiated population than non-irradiated. In summary, the results prove that irradiation by fs-laser pulses enhanced the bioavailability of curcumin and shows caspase-mediated cell death in irradiated CML cells than other populations.