Biomedical Engineering Reference
In-Depth Information
6.3.5
Annexin 5 - Directed MNP s
Bimodal contrast agents were developed to permit the detection of apoptotic cells
with both MRI and optical techniques [143]. MR contrast was provided either by the
entrapment of iron oxide particles within PEGylated micelles, or by the incorpora-
tion of Gd - DTPA - bis(stearylamide) (Gd - DTPA - BSA) lipids within the lipid bilayer
of PEGylated liposomes. Apoptosis (programmed cell death) plays an important
role in the etiology of a variety of diseases, including cancer and myocardial infarc-
tion. The visualization of apoptosis would allow both the early detection of therapy
effi ciency and an evaluation of disease progression. These contrast agents were
approximately 10 and 100nm in diameter, respectively. Additional fl uorescent
lipids were incorporated into the lipid (bi)layer of the contrast agents so as to allow
parallel detection with optical methods. Multiple human recombinant annexin A5
molecules were covalently coupled to direct the NPs specifi cally towards apoptotic
cells. Both annexin A5-conjugated contrast agents were shown to signifi cantly
increase the relaxation rates of apoptotic cell pellets compared to untreated control
cells and apoptotic cells treated with nonfunctionalized nanoparticles. Increased
relaxation rates were confi rmed, by using confocal microscopy, to originate from
an association of the contrast agents with apoptotic cells. The targeted nanoparti-
cles presented in this study, which differed both in their size and in their magnetic
properties, may have applications for the
in vivo
detection of apoptosis [143].
6.3.6
Chemotherapeutic Drugs Loaded with MNPs for Cancer Therapy
Bacterial magnetosomes (BMs) as magnetic-targeted drug carriers were used to
load antitumor doxorubicin (DOX-loaded BMs; DBMs), and the latter evaluated in
EMT-6 and HL60 cell lines [144]. The antineoplastic effects of DBMs on hepatic
cancer were evaluated both
in vitro
and
in vivo
. The administration of DBMs, DOX
and BMs led to tumor suppression rates of 86.8%, 78.6% and 4.3%, respectively,
in H22 cell-bearing mice, while mortality rates were 20%, 80% and 0%, respec-
tively. A pathological examination of the hearts and tumors revealed that both
DBMs and DOX effectively inhibited tumor growth, although DBMs displayed a
much lower cardiac toxicity compared to DOX. The DBMs were cytotoxic to H22
cells; this manifested as an inhibition of cell proliferation and c-myc expression,
and was consistent with DOX. The antitumor properties of DBMs were similar to
those of DOX, while cardiac toxicity was signifi cantly reduced in DBMs compared
to DOX. Overall, these studies provided an evaluation of the therapeutic potential
of DBMs for targeted therapy against liver cancer.
Magnetic poly(ethyl - 2 - cyanoacrylate) ( PECA ) nanoparticles containing antican-
cer drugs (cisplatin and gemcitabine) were prepared by interfacial polymerization
[145]. The amount of magnetite encapsulated inside the polymer matrix was
increased to 14.26% (w/w) by controlling the initial weight ratio of monomer/
magnetite. The amount of cisplatin encapsulated in the magnetic nanoparticle was
