S.
No Research work done
1 3 weeks after intravenous administration analysed for
following tests Serum alanine aminotransferase (ALT),
aspartate aminotransferase (AST), alkaline phosphatase
(AKP) levels, and total iron-binding capacity (TIBC)
Selected tissues were also analyzed for oxidative stress
and studied histologically to determine biocompatibility
of MNPs.
2 To assess the biocompatibility of SPION, their interaction
with two cell lines (adhesive and suspended) was
investigated using an MTT assay. Primary mouse
fibroblasts (L929, adhesive) and human leukemia cells
(K562, suspended) were used for this study
Since published reports confirm that use of the MTT
assay for measuring the toxicity of magnetite
nanoparticles has high variability and non-specificity, the
outlier detection method was applied to minimize
variability
hypothesis of this study is to make a direct correlation
between in vitro and in vivo studies by understanding the
effect of nanoparticles on the cell medium, in particular
the interaction of nanoparticles with biomolecules
Result of the study
Greater fraction of the injected iron localized in the liver and
spleen than in the brain, heart, kidney, and lung.
Serum showed a transient increase in ALT, AST, AKP levels, and
TIBC over a period of 6−24 h following MNP injection
Histological analyses of liver, spleen, and kidney samples
collected at 1 and 7 days showed no apparent abnormal changes.
SPION can cause significant changes in the cell medium, such as
denaturation of proteins, which in turn can cause toxicity.
The toxicity of uncoated SPION is found to decrease significantly
Coated nanoparticles induce lower toxicity not only due to the
presence of the biocompatible coating, but also due to the lower
adsorption sites for proteins, ions and other components in
medium.
Acceptable levels of cell viability were maintained after exposure
to PVA-coated SPION for up to 72 h at 80 mM, whereas the cells
exhibited toxic effects after exposure to bare SPION
The morphology of the treated cells differed in comparison with
the controls, particularly in the case of bare SPION
Cell clustering was observed at high SPION concentrations likely
due to the magnetostatic effect. Significant apoptosis was not
observed in cells treated with PVA-coated SPION, although
considerable levels of apoptosis were detected in cells exposed to
the bare nanoparticles.

3 Synthesized a series of SPIOs. In this report, single- and
repeat-dose toxicity were performed with SPIO to
preliminary evaluate the toxicity of SPIO. SPIO that we
manufactured has a mean particle diameter of 30 nm.
Male KM mice were used for this study.
Since no significant traces of cell death were observed with coated
SPION at low concentration,
The SPIO nanoparticle exhibited a low toxicity profile, with no
treatment-related deaths and few transient clinical signs.
SPIO was taken up and distributed in heart, spleen, liver, lung,
kidney, brain decreasingly within 24 hours after injection.

Analyses of all samples were carried out by flame atomic After repeated injections for 10days, the
absorptionspectrometry accumulation of iron on organs studied is slight, indicating that
iron is eliminated fast at 100mg/kg given subcutaneously in mice.
In the single-dose toxicity study, the mice were were
given a single subcutaneous (SC) injection of SPIO at At histopathology, no iron-positive pigment was observed in
100mg/kg. All animals were examined for mortality and macrophages of multiple organs (mainly heart, liver, spleen, lung,
clinical signs once per 2 hours.All of the animals were kidney, brain).
sacrificed 24 hours after injection and received a
complete necropsy. The iron contained in heart, spleen,
liver, lung, kidney, brain was evaluated with AAS after
Pretreatment

In the repeated dose studyt, the mice in SPIO group

received 100 mg/kg by SC injection of SPIO once a day
for 10 days.All animals were examined for mortality
and clinical signs daily. The mice were sacrificed 24
hours after last injection and received a complete
necropsy. A small part of organ tissues (heart, spleen,
liver, lung, kidney, brain) were prepared for
pathology, the rest were prepared for AAS.

4 In the present study the effect of iron oxide magnetic In animals given Fe3O4-PVP-POES-Doxo and treated with
nanoparticles (Fe3O4 nanoparticles with PVP coating) magnet, there was a visible reduction of tumor growth, during the
 complexed with Doxorubicin (Doxo) in DLA cells and
murine solid tumour was evaluated. The antitumour effect
of the complex with an externally applied magnetic field
to target the complex to the tumour site after oral
administration was also studied.
Fe3O4-PVP nanoparticles were coated with poly oxy
ethylene 25 propylene glycol stearate (POES) and then
complexed with doxorubicin to obtain Fe3O4-PVP-POES-
Doxo nanoparticles.
Male Swiss albino mice bearing transplanted DLA solid
tumor on hind legs were administered with the drug and
nanoparticle complex, orally and treated with a magnet on
the tumour for 15 min for 7 days. The hind leg
thicknesses were measured using a vernier caliper once in
three days and the tumor volume was calculated.
5 Two types of Iron Oxide, Fe3O4 and γ-Fe2O3,
were encapsulated with Chitosan by polymerizing IO
associated methacrylic acid monomer (MAA) in
the presence of CS at [NH2]/[COOH] molar ratios of 0.2.
The internalization, iron uptake, and cytotoxicity were
investigated systematically in order to explore their
potential bioapplications. Kusa O cells, mesenchymal
stem cell lines, was used for this study.
treatment period and there was no reappearance of tumour in this
group after the treatment duration, whereas animals treated with
Doxo, Fe3O4-PVP-POES, Fe3O4-PVP-POES-Doxo without
magnet exposure showed a comparable reduction in tumour
growth during the treatment period but later the tumor showed a
logarithmic growth.
Fe3 O4 - PVP POES- Doxorubicin complex showed more
cytotoxicity on DLA cells compared to Fe3 O4 - PVP or
Doxorubicin alone. Treatment of DLA cells with the nanoparticle-
doxorubicin complex resulted in higher apoptotic index than that
of treatment with doxorubicin or nanoparticles alone.
In the heart tissue of tumour bearing mice treated with Fe3 O4 -
PVP-POES- Doxorubicin without magnetic field application there
was decrease in levels of GSH and increase in the levels peroxides
of lipids ( monitored as TBARS) due to the oxidative stress
induced by the drug in heart tissue while in the animals subjected
to the applicatiotion of magnetic field following Fe3 O4 - PVP-
POES-Doxorubicin treatment the levels were similar to the control
animals suggesting alleviation of cardiotoxicity due to magnetic
targeting.
The internalization and uptake of IO nanoparticle more in the cell
incubated with magnetic field.
Viability of the cells more in the cells incubated with the Magnetic
field which doesn’t cause any morphological changes in the cells.
The chitosan-coated magnetic nanoparticles can facilitate adhesion
to the membrane of Kusa O stem cells and the cellular uptake of
IO-entrapped CS nanoparticles was enhanced under magnetization
 Prior to the internalization experiment, the with no morphology change and no toxic effect.
nanoparticles were labeled with fluorescein
isothiocyanate (FITC). Then the cells were cultured and
treated with the nanoparticle(0.005mg) and cells then
incubated at 37 oC for 3 h in the presence and absence of
a magnetic field.The cellular entry of FITC-labeled
particles was monitored by confocal laser scanning
microscopy.

Prior to the iron uptake assay, the actual amount of IO in

IO-entrapped CS nanoparticles needed to be determined.
The actual concentration of loaded IO was quantified by
dissolving the nanoparticles in 7 ml 10% HNO3 and
analyzing using AAS.After cuture of cells the
nanoparticle (0.005mg) were added to the cells and
incubated for 3 hrs with and without magnetic field after
incubation the uptake of IO were analyzed by AAS.

Cytotoxicity of nanoparticles was evaluated by MTT

assay.

6 The aim of this study was to investigate and compare The results showed that there was a high variation among different
 different nanoparticles and nanotubes regarding
cytotoxicity and ability to cause DNA damage and
oxidative stress. The study was focused on different metal
oxide particles (CuO, TiO2, ZnO, CuZnFe2O4, Fe3O4,
Fe2O3), and the toxicity was compared to that of carbon
nanoparticles and multiwalled carbon nanotubes
(MWCNT). The human lung epithelial cell line A549 was
exposed to the particles, and cytotoxicity was analyzed
using trypan blue staining. DNA damage and oxidative
lesions were determined using the comet assay, and
intracellular production of reactive oxygen species (ROS)
was measured using the oxidation-sensitive fluoroprobe
2′,7′-dichlorofluorescin diacetate (DCFH-DA).
7
nanoparticles concerning their ability to cause toxic effects. CuO
nanoparticles were most potent regarding cytotoxicity and DNA
damage. The toxicity was likely not explained by Cu ions released
to the cell medium. These particles also caused oxidative lesions
and were the only particles that induced an almost significant
increase (p = 0.058) in intracellular ROS.
For iron oxide particles (Fe3O4, Fe2O3), no or low toxicity was
observed,
ZnO showed effects on cell viability as well as DNA damage,
whereas the TiO2 particles only caused DNA damage.
The carbon nanotubes showed cytotoxic effects and caused DNA
damage in the lowest dose tested.
Reference :

Tapan K. Jain, Maram K. Reddy, Marco A. Morales, Diandra L. Leslie-Pelecky and Vinod Labhasetwar, Biodistribution, Clearance,
and Biocompatibility of Iron Oxide Magnetic Nanoparticles in Rats, Mol. Pharmaceutics, 2008, 5 (2), pp 316–327

2) Morteza Mahmoudia,, Abdolreza Simchia,b, Mohammad Imanic, Mohammad A. Shokrgozard,,Abbas S. Milanie, Urs
O. Häfelif, Pieter Stroeveg, A new approach for the in vitro identification of the cytotoxicity of superparamagnetic iron oxide
nanoparticles, Colloids and Surfaces B: Biointerfaces 75 (2010) 300–309
3) Shiyuan Liu, Yu Han, Longping Yin, Ling Long and Rui Liu, Toxicology Studies of a Superparamagnetic iron oxide
nanoparticle in vivo, Advanced Materials Research Vols. 47-50 (2008) pp 1097-1100.

4) Cherupally Krishnan Nair and Dhanya Chandrasekharan, Targeted tumor therapy with doxorubicin bound to iron oxide
nanoparticles and alleviation of drug toxicity, cancer Prevention Research 1 (Meeting Abstract Supplement), B111, November
1, 2008

5) Internalization of Iron Oxide-Entrapped Chitosan Nanoparticles, Varissaporn Mayen, Saowaluk Chaleawlert-umpon,

Krissanapong Manotham, Nuttaporn Pimpha,, Journal of the Microscopy Society of Thailand xx (1 ), 6-8 (2010)

6) Hanna L. Karlsson, Pontus Cronholm, Johanna Gustafsson and Lennart M ller, Copper Oxide Nanoparticles Are Highly Toxic:
A Comparison between Metal Oxide Nanoparticles and Carbon Nanotubes, Chem. Res. Toxicol., 2008, 21 (9), pp 1726–1732