gold nanoparticles was reported (40). Meanwhile,in the same year of 2003, another research group studied the threshold and thedynamics of thermal procedure required to effectively kill cancer cell K562using nano-second Nd-Yag laser at 532 nm (41). It was demonstratedthat only three pulses of 2-3 J/cm2 laser were necessary to killsuch cell engulfing 15-20 counts of 20 nm size gold nanoparticles. However, ifa lowered laser intensity were applied at 0.
5 J/cm2, at least 50pulses and each target cell would be required to take around 100 goldnanoparticles. The cell death was mainly credited by bubble formation aroundsingle or aggregated nanoparticles followed my underwater explosion. In 2006, laser light with a wavelength in visible region ofcontinuous wave (CW) was also demonstrated its applicability selectively fightingwith selected cancerous cells (42). The subjective nanodrugs wereswitched into 40 nm gold nanospheres conjugated with anti-EGFR antibodies. Thetargeted cancerous cells were malignant hematopoietic stem cells (HSC) and malignant human ovarian cancer cells (HOC) contrastingwith benign human skin HaCaT cells. Both cancerous cells were reportedoverexpressing in EGFR. Dark field light scattering images were taken after 30min incubation time when all three kinds of cells were carefully transferred intothe modified gold nanoparticle solutions.
Light scattering images showed thesegold nanostructures were preferentially clinging to the surface of two types ofmalignant cells while only a few spotted onto the surface of HaCat cell due toheterogeneous nonspecific distribution. Following CW visible laser treatmentagreed with the phenomena of gold nanosphere distributions: the killingthreshold for noncancerous HaCat cell was 57 W/cm2 while thethreshold for HSC and HOC were 25 W/cm2 and 19 W/cm2 respectively(Fig 5). Such significant difference between cancerous and noncancerous laserintensity requirement was mainly due to the loading ability of these threekinds of cells. As discussed in this review, gold nanosphere in diameter of 40nm had a absorbance peak around 530 nm and indubitably the more each cellcarrying such gold nanostructure, the lower laser intensity required to reachits self-destruction, as a later study indicated the temperature threshold wasin the range of 70 – 80 °C (37).
Even with these promising traits ofselectively introducing cell self-destruction, visible light itself wassuffered from high absorption rate by human body which prevented this methodapplying into curing most kinds of cancer originated from inner tissue of humanbeings, however, heat generated from light could still kill deep-seated tumorcells, not from visible light, but from NIR laser.For most in vivo therapy, targeted tumour cells were not alwayssuperficially available, which required the penetration ability to go throughthe human body with minimum energy loss and nonspecific heating. Not only goldnanoparticles but also carbon nanotubes could effectively convert NIR laserinto heat contributed to local hyperthermia. In 2005, one research group used carbonnanotube with folate moiety that preferably bound folate receptors on tumourcells with minimum binding to a nonspecific target. Such protocol followed byNIR laser treatment demonstrated its applicability of treating diseased cellsoverexpressing folate receptors (43).
Meanwhile, gold nanoshells andnanorods also approved their potential beating cancer upon exposing to NIRlaser. At least two research groups had reported they achieve promisingtargeted cell destruction via gold nanostructure specific binding and followedby CW NIR lasers treating (37) (44). Reported by El-Sayed HaCat, HSCand HOC cells pre-incubated with anti-EGFR modified gold nanorods, dark fieldlight scattering indicated these nanodrugs bound onto cancerous cellspreferably while noncancerous HaCat human skin cell only carried fewnanostructures via nonspecific binding (37).Fig 6: PTT introduced by NIR laser at 800 nm difference inkilling intensity threshold were reflected. It was found that HOC and HSC cells only required half of thelaser intensity to effectively introduce cell death of HaCat normal cells, thelaser was generated by a CW Ti: Sapphire source with a wavelength of 800 nmwhile the gold nanorods SPR peak was pre-designed to be near 800 nm (Fig 6).
Active target searching antibody bound gold nanodrugs hadbeen proved for its potential in PTT, while passive target searchingphosphatidylcholine modified gold nanorods were also demonstrated itsapplicability in a specifically heating cancerous cell to death in 2006 by aNd-Yag laser at 1064 nm (45). One year later, another research groupreported folate could not only lead carbon nanotube to find a tumor, but alsocould have the same function on gold nanorods, either (46). Afterdiseased cells were labelled under this method, a 30 J/cm2 laserbeam generated by Ti: Sapphire source was able to eradicate target with limiteddamage to surroundings. PEG conjugation (passive) and antibody conjugation (active)could also cooperate to achieve duel-targeting cancer searching mission andlead gold nanoshells to tumors with excellent selectivity (47).