title: Potential therapeutic application of gold nanoparticles in B-chronic lymphocytic leukemia (BCLL): enhancing apoptosis.
abstract: B-Chronic Lymphocytic Leukemia (CLL) is an incurable disease predominantly characterized by apoptosis resistance. We have previously described a VEGF signaling pathway that generates apoptosis resistance in CLL B cells. We found induction of significantly more apoptosis in CLL B cells by co-culture with an anti-VEGF antibody. To increase the efficacy of these agents in CLL therapy we have focused on the use of gold nanoparticles (GNP). Gold nanoparticles were chosen based on their biocompatibility, very high surface area, ease of characterization and surface functionalization. We attached VEGF antibody (AbVF) to the gold nanoparticles and determined their ability to kill CLL B cells. Gold nanoparticles and their nanoconjugates were characterized using UV-Visible spectroscopy (UV-Vis), transmission electron microscopy (TEM), thermogravimetric analysis (TGA) and X-ray photoelectron spectroscopy (XPS). All the patient samples studied (N = 7) responded to the gold-AbVF treatment with a dose dependent apoptosis of CLL B cells. The induction of apoptosis with gold-AbVF was significantly higher than the CLL cells exposed to only AbVF or GNP. The gold-AbVF treated cells showed significant down regulation of anti-apoptotic proteins and exhibited PARP cleavage. Gold-AbVF treated and GNP treated cells showed internalization of the nanoparticles in early and late endosomes and in multivesicular bodies. Non-coated gold nanoparticles alone were able to induce some levels of apoptosis in CLL B cells. This paper opens up new opportunities in the treatment of CLL-B using gold nanoparticles and integrates nanoscience with therapy in CLL. In future, potential opportunities exist to harness the optoelectronic properties of gold nanoparticles in the treatment of CLL.
authors.affiliation: Department of Biochemistry and Molecular Biology, 200 1st Street, Mayo Clinic Rochester, MN 55905, USA. mukherjee.priyabrata@mayo.edu
authors.forename: Priyabrata
authors.initials: P
authors.lastname: Mukherjee
authors.forename: Resham
authors.initials: R
authors.lastname: Bhattacharya
authors.forename: Nancy
authors.initials: N
authors.lastname: Bone
authors.forename: Yean K
authors.initials: YK
authors.lastname: Lee
authors.forename: Chitta Ranjan
authors.initials: CR
authors.lastname: Patra
authors.forename: Shanfeng
authors.initials: S
authors.lastname: Wang
authors.forename: Lichun
authors.initials: L
authors.lastname: Lu
authors.forename: Charla
authors.initials: C
authors.lastname: Secreto
authors.forename: Pataki C
authors.initials: PC
authors.lastname: Banerjee
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Yaszemski
authors.forename: Neil E
authors.initials: NE
authors.lastname: Kay
authors.forename: Debabrata
authors.initials: D
authors.lastname: Mukhopadhyay