.
Niveen M. Khashab
King Abdullah University of Sc..., Jeddah ·
Division of Physical Sciences and Engineering (PSE)
https://www.researchgate.net/profile/Niveen_Khashab/info
Professor Khashab's research interests are in design,
synthesis, and applications of "smart" programmable nanomaterials with
emphasis on the controlled release and delivery aspects of the systems.
These engineered materials are utilized for biomedical (delivery,
sensing, and imaging), industrial (nanocomposites) and environmental
(membranes synthesis) applications.
Biomedical Applications
Stimuli responsive nanomaterials are prepared to package and deliver drugs directly to diseased cells, which reduce the harm to healthy parts of the body. It also allows for the delivery of hydrophobic drugs that cannot be up taken by cells. The delivery containers range from carbon based materials to inorganic capsules such as silica nanoparticles. Sensors and imaging agents based on metallic clusters and particles are also designed for separate use or direct incorporation with the delivery system for enhanced theranostic effect.
Industrial Applications
Surface modification of nanomaterials affects many of their physical and chemical properties. Improving the dispersion and interaction of nanomaterials is a hot topic as it has direct industrial application especially in the field of nanocompsites. Interaction of functionalized nanomaterials with different polymer matrices leads to a new generation of thermally, mechanically, and/or electrically enhanced materials.
Environmental Applications
Designing nanomaterial support systems for different catalysts has impressive environmental implications as it boosts the recyclability of these catalysts, which eventually leads to “green” practices. It also increases and protects the activity of the catalysts, which makes this process commercially viable. Furthermore, incorporating the designed nanomaterials in membranes promotes their practical use for different environmental processes.
“In this project we designed liposomes that are thermosensitive. By thermosensitive, I mean we used specific functional groups within the molecule that can get inside the surface of the liposomes and cause the drug to be released,” Dr. Khashab said.
“With cancer therapy and the current anti-tumor drugs in the market, a major disadvantage is that when the drugs are taken in the body, they can go everywhere. When trying to do a kind of smart-controlled release drug nano-vehicle, we are attempting to control the delivery,” Dr. Khashab said.
Because the liposomes the team designed are heat sensitive, instead of releasing and spreading everywhere, the drug doesn’t release until it reaches the heated tumor tissue in the body. To do this, Dr. Khashab’s team used a cholesterol moiety that pins itself to the surface of the liposomes. She says using cholesterol as the “pin” was a logical choice as it makes up 30 percent of the cell membranes in the body, it is biocompatible and has a natural anchor-ability – something they needed to create what they call the “nail” or “comb” effect.
During their experiments, cholesterol modified NIPAm oligomers were used as the anchor that attached to the liposome. When they used a main-chain oligomer, it produced a “nail” effect by attaching to the surface head-to-head, and when they used a side-chain oligomer it produced a “comb” effect. Both effects proved to be efficient in the study.
“At normal body temperature, they would sit there on the surface. But if it is uptaken into a cancer cell and we increase the temperature to 40 degrees, you can monitor the ‘nail’ actually pressing inside,” Dr. Khashab said.
Rather than increasing the entire body temperature, the increase would be targeted to specific areas or tissues by external machines such as those used in hyperthermia and photodynamic therapy. As the tissues are heated, the cholesterol oligomer is aggregated, causing it to press into the lipid bilayer of the liposome. “This action of the pressing inside would release the drug inside the cancer cell essentially killing it. By this way we hope to have more control of drug release in cancer cells while keeping healthy cells safe,” Dr. Khashab explained.
Now that the team has shown the results of the their “nail” and “comb” effects on the release of liposomes in targeted areas, the next phase will be seeing how the effect works on live tissues and in various scenarios. “We were able to test and get effective results in-vitro, but the most critical step remains doing in-vivo work in small animals in order for this work to have major impact,” said Dr. Khashab.
By Michelle A. Ponto, KAUST News
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Niveen M. Khashab
King Abdullah University of Sc..., Jeddah ·
Division of Physical Sciences and Engineering (PSE)
Assistant Professor, Chemical Science
Physical Science and Engineering
Smart Hybrid Materials (SHMs)
Niveen.Khashab@kaust.edu.sa
Physical Science and Engineering
Smart Hybrid Materials (SHMs)
Niveen.Khashab@kaust.edu.sa
- PhD University of Florida, Gainesville, U.S., 2006
- BS American University of Beirut, Lebanon, 2002
https://www.researchgate.net/profile/Niveen_Khashab/info
she was born and raised in the beautiful city of Beirut
in the heart of Lebanon. The pearl of the middle east, one of the names
by which it is known, is a beautiful small city by the Mediterranean
sea. I finished high school at the Makassed Secondery School for Girls
in 1998. I was always good in chemistry so i decided to major in it. I
attended the American University of Beirut where I graduated in 2002
with a Bachelors in Chemistry. Under the guidance of Prof. Maklouf
Haddadin, I did some undergraduate research and decided that I should go
to graduate. school and pursue a phD in organic Chemistry. I choose to
go to University of Florida and work for Prof. Alan Katritzky in
Heterocyclic chemistry where I got my phD in December 2006. Deciding
where to go for a postdoc was hard but then one day I was charmed by
Prof. Fraser Stoddart after listening to one of his seminars and I
decided to join his group. Since then. I've been working with very
exciting stuff and all include the word nano!! In my free time I enjoy
hanging out with my favorite person in the whole world, my baby girl
Karen.
|
Research Interests
Professor Khashab's research interests are in design,
synthesis, and applications of "smart" programmable nanomaterials with
emphasis on the controlled release and delivery aspects of the systems.
These engineered materials are utilized for biomedical (delivery,
sensing, and imaging), industrial (nanocomposites) and environmental
(membranes synthesis) applications. Biomedical Applications
Stimuli responsive nanomaterials are prepared to package and deliver drugs directly to diseased cells, which reduce the harm to healthy parts of the body. It also allows for the delivery of hydrophobic drugs that cannot be up taken by cells. The delivery containers range from carbon based materials to inorganic capsules such as silica nanoparticles. Sensors and imaging agents based on metallic clusters and particles are also designed for separate use or direct incorporation with the delivery system for enhanced theranostic effect.
Industrial Applications
Surface modification of nanomaterials affects many of their physical and chemical properties. Improving the dispersion and interaction of nanomaterials is a hot topic as it has direct industrial application especially in the field of nanocompsites. Interaction of functionalized nanomaterials with different polymer matrices leads to a new generation of thermally, mechanically, and/or electrically enhanced materials.
Environmental Applications
Designing nanomaterial support systems for different catalysts has impressive environmental implications as it boosts the recyclability of these catalysts, which eventually leads to “green” practices. It also increases and protects the activity of the catalysts, which makes this process commercially viable. Furthermore, incorporating the designed nanomaterials in membranes promotes their practical use for different environmental processes.
Selected Publications
- "Light-on” Sensing of Antioxidants Using Gold Nanoclusters. By: Lianzhe Hu , Lin Deng , Shahad Alsaiari , Dingyuan Zhang , and Niveen M Khashab. From: Analytical Chemistry Journal, ACS, 2014 ASAP
- Low-Magnetization Magnetic Microcapsules: A Synergistic Theranostic Platform for Remote Cancer Cells Therapy and Imaging; By: Wei Zhang, Lin Deng, Guangchao Wang, Xianrong Guo, Qiujin Li, Jianfei Zhang and Niveen M. Khashab From: Part. Part. Syst. Charact. 2014 ASAP
- The Hofmeister effect on nanodiamonds: how addition of ions provides superior drug loading platform. By Yong Guo , Song Li , Wengang Li , Basem Moosa and Niveen M. Khashab. From Biomaterials Science (2014), 2(1), 84-88.
- Polyetherimide/Bucky Gels Nanocomposites with Superior Conductivity and Thermal Stability. By Chen, Ye; Tao, Jing; Deng, Lin; Li, Liang; Li, Jun; Yang, Yang; Khashab, Niveen M. From ACS Applied Materials & Interfaces (2013), 5(15), 7478-7484.
- Mechanised nanoparticles for drug delivery, K. Coti, M. E. Belowich, M. Liong, M. W. Ambrogio, Y. A. Lau, H. Khatib, J. I. Zink, N. M. Khashab, J. F. Stoddart, Nanoscale 2009, 1, 16-39.
1- Benzotriazolyl-Mediated 1,2 Shifts of Electron-Rich Heterocycles
Alan R. Katritzky, Niveen M. Khashab, Sergey Bobrov, Kostyantyn Kirichenko
J. Org .Chem. 2004, 69, 4269-4271.
2- An Effcient Method for the Preparation of Trisubstituted Guanidines Alan R. Katritzky, Niveen M. Khashab, Sergey Bobrov Helv. Chim. Acta. 2005, 88, 1664. 3- Synthesis of Mono- and Symmetrical Di-N-Hydroxy and Aminoguanidines Alan R. Katritzky, Niveen M. Khashab, Sergey Bobrov, Megumi Yoshioka J. Org .Chem 2006, 71, 6753. 4- Microwave Assisted Synthesis of Amidrazones and Amidoximes Alan R. Katritzky, Niveen M. Khashab, Nataliya Kirichenko, Anamika Singh J. Org .Chem 2006, 71, 9051. 5- Preparations of Substituted Thiosemicarbazides and N-Hydroxythioureas. Alan R. Katritzky, Niveen M. Khashab, Anna Gromova Arkivoc 2006, 266. 6- C-Imidoylation of Esters, Sulfones, Sulfoxides, Amides and Nitro Compounds Alan R. Katritzky, Niveen M. Khashab, Anamika Singh Arkivoc 2007, 263. 7- Imidoylation Reactions at Carbon Alan R. Katritzky, Niveen M. Khashab Arkivoc 2007, In press. 8- C-Amino- and C-Hydroxyimidoylation of Ketones, Esters, and Sulfones Alan R. Katritzky, Niveen M. Khashab, Danniebelle Haase, Megumi Yoshioka J. Org .Chem 2007, In press. 9- Solid Phase Peptide Synthesis Utilizing Aminoacylbenzotriazoles Alan R. Katritzky, Niveen M. Khashab, Megumi Yoshioka, Jodie Johnson, Krista Wilson, Danniebelle Haase, Chemical Biology and Drug Design 2007, Accepted. |
New smart-drug research may help target cancer therapy
Dr. Niveen M. Khashab and her team at KAUST
Smart systems are a promising way to control the release of drugs
within the body in order to produce enhanced and more targeted
treatments. In a paper recently published in
Biomaterials Science, (doi: 10.1039/c3bm60222b),
Dr. Niveen M. Khashab, Assistant Professor of Chemical Science at
KAUST, and colleagues, successfully demonstrated using thermosensitve
liposomes to control the release of a drug by turning a simple system
into a smart system.
“In this project we designed liposomes that are thermosensitive. By thermosensitive, I mean we used specific functional groups within the molecule that can get inside the surface of the liposomes and cause the drug to be released,” Dr. Khashab said.
Finding a Way to Target Drugs in the Body
Liposomes are highly used in drug delivery, but the problem is that they can’t be controlled or targeted. They are also quickly eliminated from the blood and often end up in the liver. Researchers have spent decades trying to reduce this problem. One of the ways is by studying stimuli-sensitive liposomes in hopes of finding an approach that would allow for a more controlled release– especially in cancer therapies.“With cancer therapy and the current anti-tumor drugs in the market, a major disadvantage is that when the drugs are taken in the body, they can go everywhere. When trying to do a kind of smart-controlled release drug nano-vehicle, we are attempting to control the delivery,” Dr. Khashab said.
Liposomes Triggered by Heat to Control Drug Release
There are numerous approaches to stimuli-responsive liposomes ranging from liposomes that are pH sensitive, to magnetic fields, to experimenting with temperatures. Dr. Khashab and her team focused on the latter by designing thermosensitive liposomes that have proved to be effective in their release experiments inside cells.Because the liposomes the team designed are heat sensitive, instead of releasing and spreading everywhere, the drug doesn’t release until it reaches the heated tumor tissue in the body. To do this, Dr. Khashab’s team used a cholesterol moiety that pins itself to the surface of the liposomes. She says using cholesterol as the “pin” was a logical choice as it makes up 30 percent of the cell membranes in the body, it is biocompatible and has a natural anchor-ability – something they needed to create what they call the “nail” or “comb” effect.
During their experiments, cholesterol modified NIPAm oligomers were used as the anchor that attached to the liposome. When they used a main-chain oligomer, it produced a “nail” effect by attaching to the surface head-to-head, and when they used a side-chain oligomer it produced a “comb” effect. Both effects proved to be efficient in the study.
“At normal body temperature, they would sit there on the surface. But if it is uptaken into a cancer cell and we increase the temperature to 40 degrees, you can monitor the ‘nail’ actually pressing inside,” Dr. Khashab said.
Rather than increasing the entire body temperature, the increase would be targeted to specific areas or tissues by external machines such as those used in hyperthermia and photodynamic therapy. As the tissues are heated, the cholesterol oligomer is aggregated, causing it to press into the lipid bilayer of the liposome. “This action of the pressing inside would release the drug inside the cancer cell essentially killing it. By this way we hope to have more control of drug release in cancer cells while keeping healthy cells safe,” Dr. Khashab explained.
The Difference Between the ‘Nail’ and the 'Comb’
The main difference between the “nail” and the “comb” release of the drug is the backbone shrinkage. With the “comb” effect, the side-chain sequence resulted in more lateral forces (the teeth of the comb) being pushed into the liposome as it was heated, which resulted in more of the drug being released at one time when compared to the “nail” effect.
Diagram showing the "nail" and "comb" effect.
However, their study showed that the difference in the results was not
drastic due to the limited length of the chain. The team also found
that controlling the length of the chain was another advantage of the
NIPAm oligomers. The longer the chain; the faster the release.
Transforming a Simple System into a Smart System
“Fifty percent of the efforts in my lab go towards targeted and sustained drug delivery. What was nice about this project, was that we were able to take a simple system and modify it to be a smart system,” said Dr. Khashab.Now that the team has shown the results of the their “nail” and “comb” effects on the release of liposomes in targeted areas, the next phase will be seeing how the effect works on live tissues and in various scenarios. “We were able to test and get effective results in-vitro, but the most critical step remains doing in-vivo work in small animals in order for this work to have major impact,” said Dr. Khashab.
By Michelle A. Ponto, KAUST News
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