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Issue 31, 2015
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Folate decorated delivery of self assembled betulinic acid nano fibers: a biocompatible anti-leukemic therapy

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Abstract

The objective of this study was to develop folate receptor mediated delivery of self assembled betulinic acid nano fibers (SA-BA) to human leukemic cells and to investigate their specific induction of apoptosis. The physicochemical properties of PEG conjugated SA-BA followed by conjugated with folic acid (FA–PEG–SA-BA) were examined using Fourier transform infrared spectroscopy, thermogravimetry analysis, X-ray diffraction analysis, thin layer chromatography and scanning electron microscopy. The stability of folic acid with PEG–SA-BA conjugate was higher at acidic pH, which helps to maintain the conjugate structure for internalization of folate receptor over expressing cells. FA–PEG–SA-BA showed good compatibility with normal cells. The internalization of FA–PEG–SA-BA was significantly observed in folate receptor over expressing K562 cells while showing comparatively lower impact on folate receptor lower expressing KG-1A cells. This intracellular localization of conjugate facilitated the generation of excess reactive oxygen species (ROS), followed by elevation of tumor necrosis factor alpha (TNF-α) secretion. The effective contribution of ROS and TNF-α in FA–PEG–SA-BA mediated leukemic cell death was confirmed by pretreatment of cells with the ROS scavenger (N-acetyl-L-cysteine) and pentoxifylline, a potent TNF-α blocker. The mode of leukemic cell death was confirmed by flow-cytometric analysis. We also tested the possible involvement of caspase activation in TNF-α mediated leukemic cell death by immunoflouroscence staining of apoptotic marker proteins (caspase 8 and caspase 3).

Graphical abstract: Folate decorated delivery of self assembled betulinic acid nano fibers: a biocompatible anti-leukemic therapy

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Supplementary files

Article information


Submitted
19 Jan 2015
Accepted
25 Feb 2015
First published
25 Feb 2015

RSC Adv., 2015,5, 24144-24157
Article type
Paper
Author version available

Folate decorated delivery of self assembled betulinic acid nano fibers: a biocompatible anti-leukemic therapy

S. K. Dash, S. S. Dash, S. Chattopadhyay, T. Ghosh, S. Tripathy, S. K. Mahapatra, B. G. Bag, D. Das and S. Roy, RSC Adv., 2015, 5, 24144
DOI: 10.1039/C5RA01076D

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