Antileukemic potential of PEGylated gold nanoparticle conjugated with protein toxin (NKCT1) isolated from Indian cobra (Naja kaouthia) venom

[摘要] Limited efficacy of current first-line treatment for leukemia calls attention for further development of efficient strategies. Recently, much attention has been given to nanoparticle-based drug delivery systems loaded with dual drugs to improve current disease therapies by overcoming toxicity. In the present study, we document to explore an approach to conjugate gold nanoparticles (GNPs) with protein toxin (NKCT1), a protein toxin from the Indian cobra (Naja kaouthia) venom, and to establish its antileukemic activity. GNP was prepared by NaBH4 reduction method. UV–vis spectroscopy of GNP showed the absorbance at 530 nm for plasma resonance. Dynamic light scattering (DLS) size of GNPs was 2–8 nm and the GNP-NKCT1 was 68–122 nm. CD spectra of GNP-NKCT1 showed change in percentage of β-turn as compared with NKCT1. GNP-NKCT1 significantly inhibited leukemic cell growth in dose- and time-dependent manner by two- to threefold more than NKCT1. For human leukemic lymphoma cell line and human myelogenous leukemic cell line, the IC50 dose was found to be 1.2 and 0.75 μg/ml, respectively, observed by trypan blue exclusion method and tetrazolium bromide reduction assay. Flow cytometric analysis showed appreciable number of both cell lines in early and late apoptotic stages and arrested cell cycle in the G1 phase by GNP-NKCT1. Resilient power of leukemic cell line after wound healing and migration or invasive power of the cell line was significantly low in GNP-NKCT1-treated plate than the control plate. These analyses reveal that GNP-NKCT1 possesses significant and selective anticancer activity, likely by inducing programmed cell death through mitochondrial and/or lysosomal pathway.

[发布日期] 2013-04-10

[关键词] GNP-NKCT1;Nanoparticle;Leukemic cell;Apoptosis;Flow cytometry;Cell cycle