ANTICANCER RESEARCH 30: 4075-4080 (2010)

1Department of Otolaryngology, Drew University of Medicine and Science, Los Angeles, CA 90059, U.S.A.;

2Department of Chemistry and Biochemistry, UCLA, Los Angeles, CA 90095, U.S.A.;
3California NanoSystems Institute (CNSI) at UCLA, Los Angeles, CA 90095, U.S.A.

Abstract. Background: The influence of nanoparticles on
the immune system is poorly understood. It was recently
shown that exposure to a mixture of nanodiamond (ND)- and
nanoplatinum (NP)-coated material (DPV576-C) activates
murine T-cells. This study examined the role of a dispersed
aqueous mixture of ND/NP (DPV576) in activating human
dendritic cells (DCs) in vitro. Materials and Methods:
Human monocyte-derived DCs were treated with DPV576 at
various concentrations (50, 100 and 200 μg/ml) for 24 hours
in vitro. Activation of DCs was determined by assessing the
expression of co-stimulatory and maturation markers (CD80,
CD83, CD86, HLADR), production of cytokines, and
induction of proliferation of naïve CD4 T-cells. Expression
of co-stimulatory molecules and cell proliferation were
analysed by flow cytometry and cytokine secretion by ELISA.
Results: DPV576 treatment of DCs resulted in: (i) increased
CD83 and CD86 expression on DCs, (ii) up-regulation in the
levels of DC-secreted cytokines IL-6, TNF and IL-10, and
(iii) increased ability to induce proliferation in CD4+ T-cells
which is associated with increased expression of T-cell
activation marker CD25. Conclusion: Solution containing
ND/NP (DPV576) activated human DCs and DCs-driven
CD4 naive T-cell proliferation in vitro, which may be useful
in boosting immune responses in cancer treatment.
Nanomaterials have recently become the focus of research for
their use in biomedical fields including, but not limited to,
cancer treatment and diagnosis (1, 2). Polymeric micelles,
ceramic nanoparticles, viral-derived capsid nanoparticles, and
silica nanoparticles are all promising candidates for biological

Correspondence to: Mamdooh Ghoneum, Ph.D., Charles Drew
University of Medicine and Science, Department of Otolaryngology,
1621 E. 120th Street, Los Angeles, California 90059, U.S.A. Tel: +1
3235635953, Fax: +1 3104746724, e-mail:
Key Words: Nanodiamond, dendritic cells, CD4+ cells, in vitro,

applications. Recently, a mixture of two nanomaterials,
nanodiamond (ND) and nanoplatinum (NP), was introduced
and studied for their immune modulatory effect.
NDs were first synthesized approximately 50 years ago via
a detonation synthesis by explosive decomposition of highly
explosive mixtures in a non-oxidizing medium. In this type of
synthesis, the explosive dictates the detonation characteristics
and the composition of the detonation products. NDs
synthesized via this route have a chemically inert diamond
core and a shell containing reactive functional group (3).
Recently, dispersed aqueous solutions of ND have been
synthesized. The availability of these newly produced aqueous
dispersed forms facilitates their possible use in nanomedicine
and biorelated studies (4). Current studies regarding the
medical properties of NDs in animals and humans with cancer
are motivated by positive results, observed in both in vitro
drug delivery and cell targeting experiements (5, 6). In
addition, metal nanoparticles for biotechnological applications
are increasingly becoming a focus of research. In particular,
NP particles have recently emerged as a new candidate for use
in bionanotechnology. Recent studies have shown that the
physicochemical properties of NP make it suitable for the
medical treatment of oxidative stress diseases (7),
photoactivated anticancer therapy (8) and targeted controlled
release cancer drug delivery systems (9).
Although ND/NP are promising candidates for medical
purposes, the effect of these nanoparticles on the immune
system is poorly understood. It was recently shown that aged
mice exposed to ND/NP (DPV576-C)-coated garments exhibit
increased T lymphocyte responses ex vivo (10). The present
study was undertaken to examine the ability of the ND/NP
liquid mixture (DPV576) to activate human dendritic cells
(DCs), and the DC-directed T-cell response in an in vitro culture
model. This study is focused on DCs because these cells are the
most active antigen-presenting cells capable of activating naive
T-cells, and initiating antigen-specific immune responses against
pathogens (11). These cells are capable of processing both
exogenous and endogenous antigens, and present peptides in the
context of either MHC class I or II molecules.

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