Gold nanoparticles in chemotherapy
Some of the properties that gold nanoparticles possess, such as small size, non-toxicity and non-immunogenicity make these molecules useful candidates for targeted drug delivery systems.
This procedure is known to treat small tumours that are difficult to access and avoids the drawbacks (adverse effects) of conventional methods, including the unnecessary destruction of healthy tissues.
Human breast carcinoma cells infused with metal nanoparticles in vitro have been shown to have an increase in morbidity with exposure to near infrared (NIR).
Hirsch et al observed that extreme heating in tumours would cause irreversible tissue damage including coagulation, cell shrinkage and loss of nuclear straining.
Surrounding cells were swabbed with PEG and exposed to laser treatment for detection of abnormal heating indicating areas where Au nanoshells may have gathered.
[8] Despite the unquestionable success of gold nanorods or nanoshells as photothermal agents in preclinical research, they have yet to obtain the approval for clinical use because their size is above the renal excretion threshold.
[9] In 2019, the first NIR-absorbing plasmonic ultrasmall-in-nano architecture has been reported, and jointly combine: (i) an efficient photothermal conversion suitable for multiple hyperthermia treatments, and (ii) renal excretion of the building blocks after the therapeutic action.
In certain radiological procedures such as Radiofrequency therapy, a contrast agent is injected into the targeted cancer tissue and result in increased x-ray attenuation.
This active stage leads to a state of cellular hypoxia, which causes an increased regulation of pro-angiogenesis proteins such as VEGF.
[7] As a consequence of angiogenesis, rheumatoid arthritis has been found to develop due to the greater ability to spread inflammatory proteins.
Studies by Rochelle R. Arvizo, et al. have shown that the use of AuNPs of various size and surface charge plays an important role in its inhibitory effects.
[17] In today’s biological fields, the use of nanotechnology has allowed for the indirect use of AuNPs to deliver DNA to mammalian cells; thereby reducing tumor agents and increasing efficiency of electron transfer by modulating the activity of glucose oxidase.
Current ongoing research by the Mayo Clinic laboratories includes the examination of AuNPs as messengers to deliver reagents capable of manipulating the angiogenic response in vivo.
[18] Current angiogenic inhibitors used today which are approved by the USFDA to treat cancer is Ayastin, Nexavar, Sutent and Affinitor.
[4] Studies has shown the effectiveness of this method on killing Staphylococcus aureus, which is significant human pathogen responsible for a wide range of diseases such as skin and wound infections, toxic shock syndrome, septic arthritis, endocarditis, and osteomyelitis.
In this system, the bacteria damage is caused by inducing strong laser which leads to overheating effects accompanied by the bubble-formation phenomena around clustered gold nanoparticles.
Once within the tumor microenvironment, these complexes dissociate and release the chemotherapeutic, allowing the drug to take effect and eventually cause apoptosis.
The pilot study using the Ntracker [29] gold nanorods was completed in 2012 and was used on seven canines with varying degrees of solid cancer tumors.
Their results showed that toxicity was more established in AUNPs conjugated with cationic functional groups as a consequence of electrostatic interactions with the anionic cell membrane.
[36] If large concentrations quickly clear the blood vessels, the nanoshells may accumulate in major organs (mainly the liver and spleen).
If the cooling rate for a particle is too low, the lattice heat content can be increased with moderate energy radiation (40 μJ/fs with 100-fs laser at 800 nm) to the point where gold nanorods can be melted to create spherical nanoparticles which become photothermally inactive.
[40] This decomposition has been shown using gold nanorods coated with phosphatidylcholine ligands in HeLa cells using a pulsed laser and were no longer useful for treatment due to their low NIR radiation absorbance.
[43] After using nanoparticles for photothermal therapy, it has been shown in vitro that high concentrations of reactive oxygen species (ROS) are formed within the treated cancer cells.
"[48] Also, nanoparticles from 8 to 37 nanometers have been shown to cause abnormal symptoms leading to death in mice due to medical complications in the spleen, liver, and lungs.
[48] Biosafety and biokinetics investigations on biodegradable ultrasmall-in-nano architectures have demonstrated that gold nanoparticles are able to avoid metal accumulation in organisms through escaping by the renal pathway.
[49][50] Part of the issue with these studies is the lack of reliable methods for determining the uptake of gold nanoparticles in vivo without examining the tumor site post-mortem.
This technique cannot be replicated during clinical trials, so new methods need to be developed to determine the uptake of cells to avoid higher concentrations of gold nanoparticles in the body leading to toxic effects.
[7] Chamberland et al studied the use of anti-TNF conjugated gold nanorods (AuNRs) ex vivo in rat tail joints to reduce the effect of rheumatoid arthritis.
2-nm AuNP-mercaptobenzoic acid were conjugated to a derivative of a known CCR5 antagonist, which is a small molecule that antagonize CCR5 receptor, and CCR5 is commonly used by HIV to enter the cell.
The detection-visualized fluorescence-based method is highly sensitive, simple, low cost, which could potentially apply to multi-gene detection chips.
