Archive for the ‘HOT article’ Category

Fully degradable protein nanocarriers by orthogonal photoclick tetrazole–ene chemistry

With rapid advances in nanomedicine, non-toxic, biodegradable targeted nanocarriers that can encapsulate active drugs or biological molecules and can confer controllable release of its payloads at the target sites have emerged as novel theranostic tools for more sensitive and accurate diagnostics and more effective therapies. As such, by our evolving understanding of diseases and the impact of the current nanocarriers, moving towards the development of further enhanced and smart, stimuli responsive polymers is trivial. However, it is not without challenge to design such materials in a reproductive and controlled manner. Therefore, new synthesis methods and protocols that can lead to multi-component nanocarriers of optimal size and shape that are receptive to disease pathology and biochemistry and are fully non-toxic, biodegradable and allow a targeted distribution are highly timely.

 

Keti Piradashvili et al. recently reported in Nanoscale Horizons an effective and yet simple preparation of such nanocarriers that are stable in blood plasma and are enzymatically degradable. For their preparation, a light-triggered and catalyst-free tetrazole–ene cycloaddition (TET-click) on the bio-degradable natural polymers, human serum albumin (HSA) was achieved.  First, TET was attached to HSA by Steglich amidation; and second; an inter-facial cross-linking reaction of the TET-HSA in a water-in-oil mini-emulsion was used to obtain the stable fluorescent aqueous nanocarriers by irradiation of the mixture with UV light at 254 nm. (Fig.1).

 

Figure 1. Preparation of protein nanocarriers. (a) Non-fluorescent protein–TET conjugates were cross-linked by dinorbornene in inverse mini-emulsion to obtain self-fluorescent protein nanocarriers; (b) reaction mechanism of the bioorthogonal UV-light induced 1,3 dipolar tetrazole–ene cycloaddition; (c) experimental setup with a peristaltic pump pumping the emulsion through a quartz cuvette with the UV-lamp placed in front; (d) average size of various protein nanocarriers; (e) TEM image of the protein nanocarriers. Image reproduced with permission of the Royal Society of Chemistry.

 

The synthesized nanocarriers were shown to encapsulate a high drug payload (R848) of more than 90%. Besides, the encapsulated R848 nanocarriers were highly internalized into the derived dendritic cells (BMDCs) and released in a functional manner, as well as being extremely stable. There were no signs of aggregation or degradation, even after ca. 8 months of storage, so no leakage of the R848 occurred.

 

This approach could be utilized as a platform to design a variety of encapsulation on a vast range of proteins. Further preclinical and clinical testing is needed for the clinical translation of such nanotherapeutics. Nevertheless, the efficient methods reported here could play a pivotal roll along the evolutionary and revolutionary path of nanotherapeutics.

 

Read the full article here:
Keti Piradashvili, Johanna Simon, David Paßlick, Julian R. Höhner, Volker Mailänder, Frederik R. Wurm and Katharina Landfester
Nanoscale Horiz., 2017, Advance Article. DOI: 10.1039/C7NH00062F

 

Dr. Orza is a member of the Community Board for Nanoscale Horizons. She is a Senior Research Scientist in the Laboratory of Nanomedicine at Emory Medical School, USA. She completed her Ph.D. on the development of therapeutic nanoparticles in the Department of Chemistry, Liverpool University, UK and Babes Bolyai University, Romania. Her research is focused on developing hybrid-engineered nanomaterials for biomedical applications, such as: tissue engineering and cancer treatment/diagnosis. Creative approaches to the design of such nanomaterials come from chemistry, biotechnology, biology/medicine, and engineering. Additionally, Dr. Orza is a Director and Chief Scientist at IndagoMed. LLC, USA, a company focused on creating performance products through the use of nanotechnology.

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

New magnetofluidic “tweezers” capable of manipulating a single living cell

Confocal images of a single cell under the magnetic micropen before and after turning on the external field

Single cell manipulation can provide insight into cell mechanics and adhesion, and has a crucial role in in vitro fertilization (IVF). Bartusz Grzybowski at Ulsan National Institute of Science and Technology in South Korea and his team’s new technique for this doesn’t need cells to be magnetically tagged beforehand. It also avoids the risks of heat- or stress-induced cell damage that can occur with other methods.

Grzybowski et al.’s method relies on an iron oxide nanoparticle medium in which cells are suspended. Applying an electromagnet to the magnetic medium through a micropen creates field gradients, which direct the cell to move in a certain direction. By varying how the micropen “tweezers” are positioned, cell movement can be manipulated in both 2 and 3 dimensions.

As well as controlling a single cell, the micropen can be used to pick up several cells together and guide them into regularly shaped clusters. Although it’s a long way off, this could one day be used to make IVF processes more efficient, reducing the number of potential embryos that need to be discarded. It could also be extended to manipulating bacteria and other single-celled organisms to conduct detailed studies on their behaviour.

Read the full article for free, here:
Trapping, manipulation and crystallization of live cells using magnetofluidic tweezers
J. V. I. Timonen, C. Raimondo, D. Pilans, P. P. Pillai and B. A. Grzybowski
Nanoscale Horiz., 2016, Advance Article

Susannah May is a guest web writer for the RSC Journal blogs. She currently works in the Publishing Department of the Royal Society of Chemistry, and has a keen interest in biology and biomedicine, and the frontiers of their intersection with chemistry. She can be found on Twitter using @SusannahCIMay.

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

HOT article: Porous silicon–graphene oxide core–shell nanoparticles for targeted delivery of siRNA to the injured brain

Time-gated luminescence image of injured mouse brains. Dashed white circles indicate region of penetrating brain injury. Targeted and nontargeted nanoparticles are compared. Inset: Bright field image (in gray scale) under ambient light.

A novel siRNA delivery system that could pave the way for genetic treatment of cancer, neurogenerative diseases or even HIV has been described in a new HOT article published in Nanoscale Horizons.

Over the last few years siRNA (small interfering RNA) has gained increasing attention as a new way to treat genetic diseases or viruses by silencing the genes responsible – the RNA fragments prevent the proteins that cause the illness from ever being expressed in the first place, making it the ultimate preventative therapy. However, current efforts have been hampered by the difficulty of delivering the delicate siRNA to the brain in one piece, before it’s degraded or attacked by the body’s immune defences.

This new system, developed by Michael Sailor’s team at the University of California, San Diego, uses porous silica nanoparticles as a protective carrier of the siRNA – the siRNA is hidden inside the pores of the nanoparticles where it’s protected from the body’s immune responses and harsh cell environments. A graphene oxide shell around the nanoparticles ensures that the siRNA stays safely inside them until they reach the brain. They will then release the still-intact siRNA,  where it prevents sections of DNA from producing damaging proteins.  The nanoparticles, which are fluorescent and easily tracked on their journey through the body, can be targeted to specific brain cells by attaching certain peptides; when the researchers attached rabies virus glycoprotein to the nanoparticles,  their uptake by neuronal cells doubled. The system successfully silenced genes in cell cultures – even in the presence of RNA-degrading nucleases – and, promisingly, proved capable of delivering siRNA to the brains of live mice who had suffered brain injuries. Significantly more of the siRNA-carrying nanoparticles accumulated around damaged tissues than the healthy brain tissues, and released large quantities of siRNA once they got there.

Although it’s early days, the system shows great promise for genetic therapies using siRNA. By using siRNAs to silence the genes responsible for out-of-control replication of cells, it could one day be used in the prevention of cancer – and siRNAs targeted to viral proteins could even be used to successfully treat HIV.

Read the full article here:

Porous silicon–graphene oxide core–shell nanoparticles for targeted delivery of siRNA to the injured brain
Jinmyoung Joo, Ester J. Kwon, Jinyoung Kang, Matthew Skalak, Emily J. Anglin, Aman P. Mann, Erkki Ruoslahti, Sangeeta N. Bhatia and Michael J. Sailor
Nanoscale Horiz., 2016, Advance Article, DOI: 10.1039/C6NH00082G

Susannah May is a guest web writer for the RSC Journal blogs. She currently works in the Publishing Department of the Royal Society of Chemistry, and has a keen interest in biology and biomedicine, and the frontiers of their intersection with chemistry. She can be found on Twitter using @SusannahCIMay.

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)