Biomedical Engineering Reference
In-Depth Information
observed for all types of cells in the absence of nanoparticles at four times energy required to kill the
malignant cells with anti-EGFR/Au conjugates. Gold nanoparticles can thus offer a novel class of
selective photothermal agents using laser at low power.
Novel optically active reagents have been used for simultaneous molecular imaging and photo-
thermal cancer therapy. It is desirable to use these agents that are active in the near-infrared (NIR)
region of the radiation spectrum to minimize the light extinction by intrinsic chromophores in native
tissue. Gold nanorods with suitable aspect ratios (length/width) can absorb and scatter strongly in the
NIR region (650-900 nm). In an
in vitro
study
[29]
, gold nanorods were evaluated as novel contrast
agents for both molecular imaging and photothermal cancer therapy. Nanorods were synthesized and
conjugated to anti-EGFR monoclonal antibodies and incubated in cell cultures with a nonmalignant
epithelial cell line and two malignant oral squamous carcinoma cell lines. The anti-EGFR antibody-
conjugated nanorods bound specifically to the surface of the malignant-type cells with much higher
affinity due to the overexpressed EGFR on the cytoplasmic membrane of the malignant cells. As a
result of the strongly scattered red light from gold nanorods in dark field, the malignant cells were
clearly visualized and diagnosed from the nonmalignant cells. It was found that, after exposure to
continuous red laser at 800 nm, malignant cells required about half the laser energy to be photother-
mally destroyed than the nonmalignant cells. Thus, both efficient cancer cell diagnostics and selective
photothermal therapy of cancer cells were realized at the same time. The potential use of gold nano-
spheres in fluorescence-based detection and photothermal therapy of oral cancer cells was reported
later
[30,31]
. In a recent study
[32]
, it was shown that nuclear targeting of gold nanoparticles in can-
cer cells induced DNA damage, causing cytokinesis arrest and apoptosis (cell death). By properly
conjugating gold nanoparticles with specific targeting peptides, these nanoparticles were selectively
transported to the nuclei of cancer cells inducing DNA damage and cell death. In another study
[33]
,
it was shown that gold nanoparticles enhanced the radiation therapy of a radioresistant and highly
aggressive mouse head and neck squamous cell carcinoma model.
19.7.2
Liposomes in Oral Cancer Treatment
Liposomes are small artificial spherical vesicles made from naturally occurring nontoxic phospholip-
ids and cholesterol. There are four major types of liposomes
[34]
. Conventional liposomes are either
neutral or negatively charged. Sterically stabilized “stealth” liposomes carry polymer coatings to
obtain prolonged circulatory duration. Immunoliposomes have specific antibodies or antibody frag-
ments on their surface to enhance target-specific binding. Cationic liposomes interact with negatively
charged molecules and condense them to finer structure, thereby carrying them externally rather
than encapsulating the molecules within. Owing to their size, biocompatibility, hydrophobicity, and
ease of preparation, liposomes serve as promising systems for drug delivery. Their surfaces can be
modified by attaching poly(ethylene glycol) (PEG) units to enhance the circulation time in blood-
stream. Liposomes can also be conjugated with ligands or antibodies to improve their target specifi-
city (
Figure 19.2
). Liposomes have been shown to be excellent carriers for target-specific delivery
of tumor-specific antibodies, peptides, and anticarcinogenic drugs for treating head and neck carci-
noma cells. Drugs like doxorubicin
[35]
, all-trans retinoic acid (atRA)
[36]
, Gefitinib
[37]
, cetuxi-
mab
[38]
, tirapazamine
[38]
, tumor-specific antibodies like cetuximab
[37]
have been evaluated for
their efficacy using liposomes as carriers. Gene therapy is a new therapeutic approach in which defec-
tive genes are replaced with functional ones, or the delivered genes can specifically kill cancer cells.
