Gold nanoparticles: Emerging paradigm for targeted drug delivery system

Anil Kumara, b, 1, Xu Zhanga, 1, Xing-Jie Lianga

The application of nanotechnology in medicine, known as nanomedicine, has introduced a plethora of nanoparticles of variable chemistry and design considerations for cancer diagnosis and treatment. One of the most important field is the design and development of pharmaceutical drugs, based on targeted drug delivery system (TDDS). Being inspired by physio-chemical properties of nanoparticles, TDDS are designed to safely reach their targets and specifically release their cargo at the site of disease for enhanced therapeutic effects, thereby increasing the drug tissue bioavailability. Nanoparticles have the advantage of targeting cancer by simply being accumulated and entrapped in cancer cells. However, even after rapid growth of nanotechnology in nanomedicine, designing an effective targeted drug delivery system is still a challenging task. In this review, we reveal the recent advances in drug delivery approach with a particular focus on gold nanoparticles. We seek to expound on how these nanomaterials communicate in the complex environment to reach the target site, and how to design the effective TDDS for complex environments and simultaneously monitor the toxicity on the basis of designing such delivery complexes. Hence, this review will shed light on the research, opportunities and challenges for engineering nanomaterials with cancer biology and medicine to develop effective TDDS for treatment of cancer. The application of nanotechnology in medicine, known as nanomedicine, has introduced a plethora of nanoparticles of variable chemistry and design considerations for cancer diagnosis and treatment. One of the most important field is the design and development of pharmaceutical drugs, based on targeted drug delivery system (TDDS). Being inspired by physio-chemical properties of nanoparticles, TDDS are designed to safely reach their targets and specifically release their cargo at the site of disease for enhanced therapeutic effects, thereby increasing the drug tissue bioavailability. Nanoparticles have the advantage of targeting cancer by simply being accumulated and entrapped in cancer cells. However, even after rapid growth of nanotechnology in nanomedicine, designing an effective targeted drug delivery system is still a challenging task. In this review, we reveal the recent advances in drug delivery approach with a particular focus on gold nanoparticles. We seek to expound on how these nanomaterials communicate in the complex environment to reach the target site, and how to design the effective TDDS for complex environments and simultaneously monitor the toxicity on the basis of designing such delivery complexes. Hence, this review will shed light on the research, opportunities and challenges for engineering nanomaterials with cancer biology and medicine to develop effective TDDS for treatment of cancer.

Horse Genome Is Oldest Ever Sequenced

Two pieces of the 700,000-year-old horse bone used for sequencing LUDOVIC ORLANDO Researchers have generated a complete genome sequence from the bone of a horse that lived roughly 700,000 years ago, according to a study published today (June 26) in Nature. The data represent the oldest whole genome ever sequenced, almost 10 times older than the previous record "the genome of a 80,000-year-old hominid from the Denisova cave in Siberia. The genome has also provided new perspective on several aspects of horse evolution. The study offers "the tantalizing proposition that complete genomes several millions of years old may be recoverable, given the right environmental conditions," wrote David Lambert of Griffith University in Australia and Craig Millar of the University of Auckland, Zealand, in an accompanying commentary. Indeed, even in temperate environments it may be possible to recover DNA that is half a million years old, said lead author Ludovic Orlando of the Center for GeoGenetics in Copenhagen, Denmark, speaking at a press conference held at the World Conference of Science Journalists in Helsinki, Finland. That opens up the possibility of getting genomic information from ancestral human specimens like Homo heidelbergensis and Homo erectus. "Such genomic information, in combination with the Denisovan and Neanderthal genomes, would undoubtedly shed light on the evolution of humans and our hominin ancestors," wrote Lambert and Miller. In 2003, Orlando and colleagues unearthed a fossilized fragment of bone from the permafrost in the Yukon Territory, Canada. The bone turned out to be from the leg of a horse and was found to date from approximately 560,000–780,000 years ago. Using samples taken from the bone fragment, the researchers performed sequencing with the second-generation Illumina machine, as well as the Helicos platform, a third-generation tool that 53 enables single-molecule sequencing without previous amplification, thereby reducing the risk of contamination and increasing access to small fragment of endogenous DNA. Though the proportion of horse DNA in the sample read by the Helicos platform was still only 4.21 percent "compared to 70 percent for Denisovan man "it was enough to generate a whole draft genome. For comparison, the researchers also sequenced the genome of a 43,000-year-old horse, five contemporary domesticated horse breeds, a donkey, and a Prezwalski’s horse, which is thought to be the last surviving truly wild horse on the planet. The data were used to address several question in horse evolution. First, the researchers calculated the time to the most recent common ancestor of all species in the Equus genus, including modern-day horse, donkeys, and zebras, to between 4 and 4.5 million years ago"twice as old as previously thought. "So they have about twice as long to diversify into what we know as the Equus groups today," said study coauthor Eske Willerslev, also at the Center for GeoGenetics. The team also found no genomic evidence to suggest that the Prezwalksi’s horse has mixed with domestic horses, thereby confirming that it is the last truly wild horse. "There is no domestic genetics present in these horses," said Willerslev. Furthermore, the Prezwalksi’s horse has retained significant genetic diversity, good news for the future of the species. The researchers also found evidence in domestic horses for the positive selection of the genes associated with olfaction and the immune system, suggesting these might be genetic signatures of domestication.

For most researchers, however, the real significance of the study lies in the fact that it pushes the timeframe for paleogenomics back by almost 10 times. ―Until this study, many experts would have thought that it was impossible to recover a genome from a sample of this age because of the rapid degradation of DNA into ever shorter fragments that occurs following the death of an organism," wrote Lambert and Miller in their commentary.

The main reason such a feat was possible is that the bone was buried in the extreme cold of the permafrost. But although it was in relatively good shape for such an old sample, the DNA was still  "super poorly preserved," added Willerslev. Indeed, it was only thanks to recent advances in DNA sequencing technology"including single-molecule sequencing and improvements on the informatics side "that the researchers were able to get a whole genome from the surviving short DNA fragments. Intriguingly, they also used mass spectrometry techniques to sequence 73 proteins, including some blood peptides such as coagulation factors, suggesting that proteomics approaches might also be used on well-preserved ancient specimens."We were amazed about the quality of the sample," said Orlando. "We not only beat the record for [oldest] genome characterization by almost an order of magnitude . . . we also discovered that a whole bunch of omics approaches can be used to characterize the deep evolutionary past."

L. Orlando et al., “Recalibrating Equus evolution using the genome of an early Middle Pleistocene horse,” Nature, doi:10.1038/nature12323, 2013.

Business Line: News / Science: Grunt work: Scientists decode pig genome

Scientists said they had laid bare the genetic code of the pig, revealing that besides providing ham, bacon and sausages, the domestic swine may also be useful in fighting human diseases.

Pigs and humans share 112 DNA mutations which in man have been linked to obesity, diabetes, dyslexia, Parkinson’s and Alzheimer’s, a team from the United States and Europe found.

“We have the chance to study (in pigs) how these genes interact with others to cause obesity, diabetes or other diseases,” Denis Milan, Head of Animal Genetics at France’s National Institute for Agricultural Research (INRA), told AFP yesterday.

“This suggests that for some studies, including testing drugs and therapies, pigs may be a useful model for predicting outcomes in humans,” added Co-Author Alan Archibald from the University of Edinburgh.

The domestic pig, Sus scrofa domesticus, is already used extensively in medical research, due to its anatomical similarity to humans.

Pig heart valves are being used by surgeons to replace faulty human ones.

“Now we can use pigs for looking at genetic diseases” as well, said co-author Lawrence Schook from the University of Illinois.

This could include “making genetically modified animals to create human disease models”.

The sequencing of the genome also holds promise for improvements in the pig’s more traditional role since being domesticated over 10,000 years ago — that of serving as dinner.

Scientists now have more tools at their disposal to breed a new generation of super-pigs that will yield more meat for less feed, bear more piglets and resist disease better.

The team has developed a test with which they can identify individual pigs with a genetic predisposition to growing fat fast, survive long and bear many offspring.

The sequencing project, which saw the domestic pig’s genome compared to that of the wild boar, human, mouse, dog, horse and cow, also revealed a “clear” genetic distinction between European and Asian pigs.

The ancestor of the domestic pig, which resembles today’s wild boar, first emerged in Southeast Asia and migrated across Eurasia.

The two groups were separated for so long, including by ice ages, that they became almost sub-species.

The findings add to evidence “that pigs were independently domesticated in western Eurasia and East Asia”, the authors wrote in the paper published in the journal Nature.

They also found that of the species examined, pigs had the most olfactory receptor genes — underlining the importance of smell in the scavenger animal’s lifestyle.

The swine also had fewer bitter taste receptors, meaning that “pigs can eat food that is unpalatable to humans” — another reason they have become such a highly valued farm animal.

Keywords: Genetic code Pig, ham, bacon, sausages, 112 DNA mutations, obesity, diabetes, dyslexia, Parkinson’s disease, Alzheimer's Disease, Denis Milan, Head of Animal Genetics, France’s National Institute for Agricultural Research, Co-Author Alan Archibald, University of Edinburgh, Sus scrofa domesticus, medical research, Lawrence School, University of Illinois, super-pigs, Southeast Asia, Eurasia, Nature,