gold studied the threshold and the dynamics of

gold nanoparticles was reported (40). Meanwhile,
in the same year of 2003, another research group studied the threshold and the
dynamics of thermal procedure required to effectively kill cancer cell K562
using nano-second Nd-Yag laser at 532 nm (41). It was demonstrated
that only three pulses of 2-3 J/cm2 laser were necessary to kill
such cell engulfing 15-20 counts of 20 nm size gold nanoparticles. However, if
a lowered laser intensity were applied at 0.5 J/cm2, at least 50
pulses and each target cell would be required to take around 100 gold
nanoparticles. The cell death was mainly credited by bubble formation around
single or aggregated nanoparticles followed my underwater explosion.

In 2006, laser light with a wavelength in visible region of
continuous wave (CW) was also demonstrated its applicability selectively fighting
with selected cancerous cells (42). The subjective nanodrugs were
switched into 40 nm gold nanospheres conjugated with anti-EGFR antibodies. The
targeted cancerous cells were malignant hematopoietic stem cells (HSC) and malignant human ovarian cancer cells (HOC) contrasting
with benign human skin HaCaT cells. Both cancerous cells were reported
overexpressing in EGFR. Dark field light scattering images were taken after 30
min incubation time when all three kinds of cells were carefully transferred into
the modified gold nanoparticle solutions. Light scattering images showed these
gold nanostructures were preferentially clinging to the surface of two types of
malignant cells while only a few spotted onto the surface of HaCat cell due to
heterogeneous nonspecific distribution. Following CW visible laser treatment
agreed with the phenomena of gold nanosphere distributions: the killing
threshold for noncancerous HaCat cell was 57 W/cm2 while the
threshold for HSC and HOC were 25 W/cm2 and 19 W/cm2 respectively
(Fig 5). Such significant difference between cancerous and noncancerous laser
intensity requirement was mainly due to the loading ability of these three
kinds of cells. As discussed in this review, gold nanosphere in diameter of 40
nm had a absorbance peak around 530 nm and indubitably the more each cell
carrying such gold nanostructure, the lower laser intensity required to reach
its self-destruction, as a later study indicated the temperature threshold was
in the range of 70 – 80 °C (37). Even with these promising traits of
selectively introducing cell self-destruction, visible light itself was
suffered from high absorption rate by human body which prevented this method
applying into curing most kinds of cancer originated from inner tissue of human
beings, however, heat generated from light could still kill deep-seated tumor
cells, not from visible light, but from NIR laser.

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For most in vivo therapy, targeted tumour cells were not always
superficially available, which required the penetration ability to go through
the human body with minimum energy loss and nonspecific heating. Not only gold
nanoparticles but also carbon nanotubes could effectively convert NIR laser
into heat contributed to local hyperthermia. In 2005, one research group used carbon
nanotube with folate moiety that preferably bound folate receptors on tumour
cells with minimum binding to a nonspecific target. Such protocol followed by
NIR laser treatment demonstrated its applicability of treating diseased cells
overexpressing folate receptors (43). Meanwhile, gold nanoshells and
nanorods also approved their potential beating cancer upon exposing to NIR
laser. At least two research groups had reported they achieve promising
targeted cell destruction via gold nanostructure specific binding and followed
by CW NIR lasers treating (37) (44). Reported by El-Sayed HaCat, HSC
and HOC cells pre-incubated with anti-EGFR modified gold nanorods, dark field
light scattering indicated these nanodrugs bound onto cancerous cells
preferably while noncancerous HaCat human skin cell only carried few
nanostructures via nonspecific binding (37).

Fig 6: PTT introduced by NIR laser at 800 nm difference in
killing intensity threshold were reflected.

 

It was found that HOC and HSC cells only required half of the
laser intensity to effectively introduce cell death of HaCat normal cells, the
laser was generated by a CW Ti: Sapphire source with a wavelength of 800 nm
while the gold nanorods SPR peak was pre-designed to be near 800 nm (Fig 6).

Active target searching antibody bound gold nanodrugs had
been proved for its potential in PTT, while passive target searching
phosphatidylcholine modified gold nanorods were also demonstrated its
applicability in a specifically heating cancerous cell to death in 2006 by a
Nd-Yag laser at 1064 nm (45). One year later, another research group
reported folate could not only lead carbon nanotube to find a tumor, but also
could have the same function on gold nanorods, either (46). After
diseased cells were labelled under this method, a 30 J/cm2 laser
beam generated by Ti: Sapphire source was able to eradicate target with limited
damage to surroundings. 

PEG conjugation (passive) and antibody conjugation (active)
could also cooperate to achieve duel-targeting cancer searching mission and
lead gold nanoshells to tumors with excellent selectivity (47).