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Quantum dot in detection and
treatment of cancer
Easir Abedin
Semiconductor quantum dots (QDs) are nano-particles that have attracted widespread interest in medicine and biology due to their unique optical and electronic properties. These properties, especially their reduced tendency to photobleach and the dependence of their fluorescence wavelength on their size, make them suitable for fluorescent probing applications to detect cancer biomarkers in vitro and in vivo in cells/tissues/whole body. There is considerable interest among researchers due to the recent developments in QD technology. QDs have been encapsulated in amphiphilic polymers and bound to tumour -targeting ligands and drug delivery vesicles for targeting, imaging and treating tumour cells. Present efforts are focussed on exploring the massive multiplexing capabilities of the QDs for the simultaneous detection of multiple cancer biomarkers in blood assays and cancer tissue biopsies. These advances in the QD technology have unravelled a great deal of information about the molecular events in tumour cells and early diagnosis of cancer.
Early screening of cancer is desirable as most tumours are detectable only when they reach a certain size when they contain millions of cells that may already have metastasised. Currently employed diagnostic techniques such as medical imaging, tissue biopsy and bioanalytical assay of body fluids by enzyme linked immunosorbent assay (ELISA) are insufficiently sensitive and specific to detect most types of early-stage cancers. Moreover, these assays are labour intensive, time consuming, expensive and don’t have multiplexing capability. On the other hand, QD based detection is rapid, easy and economical enabling quick point-of-care screening of cancer markers. QDs have got unique properties which make them ideal for detecting tumours.
These include intense and stable fluorescence for a longer time; resistance to photobleaching , large molar extinction coefficients, and highly sensitive detection due to their ability to absorb and emit light very efficiently. Due to their large surface area-to-volume ratio, a single QD can be conjugated to various molecules, thus making QDs appealing for employment in designing more complex multifunctional nanostructures. Various types of biomarkers such as proteins, specific DNA or mRNA sequences and circulating tumour cells have been identified for cancer diagnosis from serum samples. Therefore, QD based multiplexed approach for the simultaneous identification of many biomarkers would lead to more effective diagnosis of cancer. QDs have been covalently linked to various biomolecules such as antibodies, peptides, nucleic acids and other ligands for fluorescence probing applications . Some of the applications of QDs in biology [20-32] along with their tremendous potential for in vivo molecular imaging have already been explored.
The most commonly used QD system is the inner semiconductor core of CdSe coated with the outer shell of ZnS. The ZnS shell is responsible for the chemical and optical stability of the CdSe core. QDs can be made to emit fluorescent light in the ultraviolet to infrared spectrum just by varying their size. The wavelength of fluorescence of the QD depends on its energy gap (i.e. the difference between the excited and the ground state) which is determined by the size of the QD . QDs have narrow spectral line widths, very high levels of brightness, large absorption coefficients across a wide spectral range, high photostability and capability of multiplexed detection. They are very bright and stable even under complex in vivo conditions that make them suitable for advanced molecular and cellular imaging, drug delivery and for highly sensitive bioassays and diagnostics . Highly sensitive real-time imaging with greater resolution and tracking of single receptor molecules on the surface of living cells have been made possible by QD bioconjugates . Various applications of quantum dots are stated in figure 1. In most of the cases, functional QD conjugates for cancer detection are composed of a semiconductor core (CdSe, CdTe); an additional shell such as ZnS in the case of CdSe QDs having a higher band gap than CdSe to increase quantum yield; a water soluble hydrophilic coating; and, functionalized antibodies or other biomolecules complementary to the target cancer markers at the tumour sites.
Applications of Quantum dots
Advances in Quantum Dot Technology for the Diagnosis of Cancer
In the early stages, QDs were employed for several imaging applications in place of organic dyes. But the tremendous potential of these materials was realized when it was observed that they kept on emitting intense fluorescent light for weeks. This was a major technological advancement for microscopic imaging, which helped in unfolding many cellular processes. In the subsequent stages of development, researchers developed a keen interest in the QD technology and started exploring their applications in different fields. Different QDs composed of the same material but of different sizes had been made, which can generate different colors after activation by light of a single wavelength. It was then demonstrated that QDs tagged with biomolecules such as antibodies, peptides etc. can be employed to detect specific molecules on the cell surface or inside the cell.
Targeting tumour cells
The use of QD-peptide conjugates to target tumour vasculatures in vivo was reported by Akerman and coworkers. They employed ZnS-capped CdSe QDs and showed the targeting capabilities of QDs coated with different peptides. QDs coated with a lung-targeting peptide accumulated in the lungs of the mice after intravenous injection. The peptide got bound to membrane dipeptidase on the endothelial cells in lung blood vessels. In the second case, QDs coated with a targeting peptide got bound to blood vessels and tumour cells in certain tumours. In the third case, QDs coated with a targeting peptide got bound to lymphatic vessels and tumour cells. The group also showed that adding PEG to the outer coating of the QDs prevented nonselective accumulation of QDs in reticuloendothelial tissues.
Identifying breast cancer cells
A research team from Quantum Dot Corporation and Genentech proved the potential of QDs to identify live breast cancer cells that are likely to respond to an anti-cancer drug. They employed QDs linked to immunoglobulin G (IgG) and streptavidin to label Her2 cancer marker present on the surface of live breast cancer cells and also explored the QD technology for the simultaneous labelling of Her2 on the cell surface and in the nucleus. The researchers simultaneously detected two cellular targets with a single excitation wavelength thereby showing that different colored QDs i.e. QDs of different sizes but same materials could be used together to distinguish different parts of a single cell thus leading to multiplex target detection.
Quantum dot based drug delivery
Shuming Nie and coworkers modified the original CdSe QD with an impermeable coating of polymer that prevented the leaking out of highly toxic cadmium ions from the QD conjugate and provided a means to chemically attach tumour -targeting molecules and drug delivery functionality to the QD conjugate. The group is working on the development of a drug delivery system targeted to the cancer cells. It is developing QDs conjugated to peptides or antibodies to target human tumour cells growing in mice. QDs would be tuned to radiate in the infrared region to prevent tissue damage from the QDs energy emissions. QDs conjugated to peptide/antibodies specific against the cancer marker on the surface of the target cancer cells would be made to release the drug only when hit with laser light. This would allow control of the cells that will receive the toxin, thus minimizing side effects. There are also on-going efforts by the group to extend the wavelength of fluorescence of the QDs above 900 nm since there are hardly any biomolecules which emit above this wavelength.
Today with the help of QD technology, cancer researchers are capable of observing the fundamental molecular events occurring in the tumour cells. This has been made possible by tracking the QDs of different sizes and thus different colors, tagged to multiple different biomoleules, in vivo by fluorescent microscopy. QD technology holds a great potential for applications such as in nanobiotechnology and medical diagnostics where QDs could be used as labels. But still the use of QDs in humans requires extensive research to determine the long-term effects of administering QDs.
Future of quantum dots
Researchers have started the exploration of QDs just from the last two decades. The field is still in its infancy but it has captivated scientists and engineers due to the unique optical and electronic properties of QDs. QDs have revolutionized the field of molecular imaging. The forthcoming years would see their potential applications in different fields. One of the major areas of impact is surely the intracellular imaging of live cells. The technology will provide new insights in understanding the pathophysiology of cancer, and in imaging and screening tumours. QDs will definitely be one of the components of the envisioned multifunctional nanodevices that can detect diseased tissue, provide treatment and report progress in real time.
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Campus Capers
Endowment plunges
Rayyan Kamal
The other day we received an e-mail from the President of the University informing us that the value of Yale’s endowment had plunged 25 percent to $17 billion between June 30 and now. For a fund that has produced positive returns even after the Dotcom Bubble burst, this is particularly distressing news. In the wake of the current financial market conditions, the decline did not come as a surprise – it was the magnitude of the decline that was particularly shocking. I guess David Swensen, Yale’s Chief Investment Officer and god among the finance geeks on campus, is fallible too. But there is no denying that he has an impeccable track record. He single handedly grew the university’s endowment from around $7 billion in 1998 to $22 billion in 2007.
For the uninitiated, University Endowments function like other institutional funds. Initially, the money for them comes from donations. When a sufficient amount has been gathered, a principal amount is set aside and not touched. The remainder, usually not more than five percent of the total endowment, is invested and any positive returns are reinvested. In reality, the endowment is the sum of multiple endowments, each with its own specific purpose. There are endowments for top teaching positions, financial aid for students and the construction and renovation of buildings.
President Levin discussed the measures that would be taken to counter this decline: salary raises will be slowed, new jobs will be given out with more frugality, new construction projects will be indefinitely delayed. In fact, the construction of a new sleek, modern building for the Graduate School of Management that had been talked about for ages has been halted, as has the construction of the two new residential colleges that would increase the size of the student body (not to mention the university’s income from tuition fees).
Though losing $6 billion is no joke, President Levin rightly pointed out that neither is it a genuine catastrophe if you’re left with $17 billion after the drop. In his e-mail he was quick to remind students that the University Endowment only surpassed the $17 billion mark three years ago and it’s not as if Yale was struggling to meet ends meet before that. One of my friends wondered if the higher-ups like President Levin or CIO David Swensen would be subjected to any pay cuts. This is a good question, the answer to which I’m curious to know.
My decidedly ultra-leftist friend also went on his favourite rant – the diatribe against capitalism. He thinks that governments should enforce a maximum wage just as they enforce a minimum wage in the United States. An interesting idea, but then would college students have the incentive to go into investment banking and act as lackeys to Wall Street’s denizens? Maybe the impossibly high wages CEO’s receive accurately captures the value of their work? Even if they don’t and only the US implements this reform, there will be an exodus of deep-pocketed bosses to the Hong Kongs, Switzerlands, and Cayman Islands of the world. You just can’t win with these people.
Rayyan Kamal is a senior at Yale University.
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Australia provides funds to support safe drinking water and hygienic sanitation
Holiday Report
Australian government under its Direct Aid Program (DAP) has sanctioned Tk 14 lakh to two Bangladeshi NGOs- Jano Sheba Kendra (JSK) and Society for People’s Actions in Change and Equity (SPACE).
SPACE will spend its share of taka seven lac to provide arsenic-free safe drinking water to families of three villages in Manikganj through low cost and non chemical-based water treatment. About 3000 people including vulnerable children and women from the three villages will benefit from this project. Earlier this year, SPACE successfully installed 120 ecologically friendly toilets with DAP funding in Manikganj and Gazipur.
JSK has received a total of Tk 6.98 lac to provide hygienic sanitation facilities in five schools in Raipur Upazilla, Lakshmipur district. Along with providing sanitation facilities, JSK will also raise awareness about good hygiene practices among school children and organize advocacy meetings and workshops for members of the community as a whole.
The Australian High Commissioner, Douglas Foskett, handed over cheques to the executives of two NGOs.
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Stray reflections on the milieu-I
Sohel N Rahman
A personal matter. I’m sure that’s how I responded five plus years ago, or used words to that effect. With a glass of lemonade in hand, I gauged the crowd with passable accuracy, and decided not to explain why I came back to perhaps the only place where I shouldn’t be asked such questions. I didn’t need a visa to get here, so why ask a question that you don’t really want the answer to? Hence the use of a typical phrase without playing too many notes not too many people have the time for. At least not with the casual verve of dinner party chitchat before the so-called conversation waltzes over to better, less demanding pastures across the room a couple of awkwardly stretched minutes later. Conversations certainly easier on the fashionably inattentive mind, minds perhaps also a little on the tipsy side, are always on menu around here, and a real answer to the question, let’s just say, will complicate matters a little.
Strangely, that’s what I’m still saying five years after moving back to Dhaka. Ambiguous enough to be a good answer, and loaded enough to be a conversation stopper – in a pleasant, gentle, uncomplicated sort of way of course. That’s important, now even more so because there seems to be something different in the air around us, and nobody thinks that they’re just making all this up anymore. Something much anticipated yet somehow a little unexpected now that it’s finally here. Something that tells us that the time has finally come for the input to match the expectation, meaning what’s in the news these days may actually be the beginning of the much anticipated reversal of our misfortune. The misfortune of being led by the iniquitous and the wretchedly shortsighted for the past twentysomething years. These are exciting times because the proverbial chicken of our collective discontent has finally come home to roost.
“So, why did you move back?” was the question and it continues to be despite the five plus years since the first time I heard those exact words. Five plus years in a wild place where you have to tame the beast yourself before daring to ride him off to that picturesque tomorrow. Definitely not a place for those wish to simply walk into an air-conditioned showroom with a bag full of credit – deserved, ill-gotten or inherited, doesn’t matter as long as that bag is full – and drive off into that promising sunset in a comfortable vehicle of their choice. I knew that when I decided to come back. After ten plus years of surviving in the American corporate jungle, spending money after work and waiting to spend more on the weekends, and feeling hurried into savouring the last few drops of squeezed out freedom on Sunday afternoons before plunging into the next workweek just around the corner – I felt ready for the new frontier that I owed to myself to come back to. Don’t get me wrong, I’m not dissing my career there. I learnt a lot about the job, about myself, and my ability to like, even feel passionate about the job in order to keep my sanity not too far from where it should be. I felt it was time for me to try and apply my professional skills here, where they can make more of a difference. I watched a couple of decades pass by in suburban DC, Paris and Northern California, and it was time to come home.
In retrospect, I was not entirely delusional despite some setbacks, now chalked up as a weird sort of culture shock you overcome easily – it’s your original culture after all. Good things also happened, and an unbreakable optimism, quite common amongst my fellow Bangladeshis, kept rekindling hope whenever that hope seemed extinguished because of the wide variety of unexpected gusts of the local wind that no longer surprise me as much as they used to in the beginning. It still does with the promise that this optimism will always accompany reasoned faith in God, and wilful submission to God’s will. No, like most Bangladeshis, thank God, clearly I’m not one of those guys who want to silence other voices in Islam, or deny non-Muslims justice and equal treatment under the law, an outrageous concept indeed. Playing the intermediary between God and man’s salvation, exercising unilateral power over others without the possibility of a role reversal, not understanding the inherent indignity in speaking for someone else, and using religion as cover – definitely not my cup of tea. I just want to clear that up.
If anything, those unexpected moments and easy deceptions ultimately led me to that honest look in the mirror of one’s own limitations. A little detour, though unwanted at the time, I’m glad I took the time to take. The hustle and bustle and not a single dull moment since, I’d say. Maybe not too many sweet moments in there either. At least not the kind of sweet moments that fall on your lap on their own, the kind that don’t require peeling, plucking and more often than not – decoding and deciphering. I’m not really bitching about life here in the Dhaka metropolitan area. Far from it, I like living here. I’m talking about a question that continues to find new life in small talk whenever I, or other returnees like myself are around. The question, much to my annoyance, doesn’t seem to get old. That’s rare in my neck of the woods right here in the Gulshan-Banani-Baridhara ghetto for the obscenely privileged and sadly, the equally irresponsible to nation, community, and ultimately to one’s own existential essence. Five plus years and still not old in a place where trends and the average attention span fluctuate with greater frequency than electricity in less affluent neighbourhoods in Dhaka. Now that’s really something.
(More next week)
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No more powder milk for the children
Holiday Report
Breast-milk is the most comprehensive diet feed to ensure full nutrition and growth of a baby. Breast milk is the best feed to give them appropriate nutrition and growth up till the first six months.
This was stressed in a seminar arranged last week in the city by Rainbow Nari O Shishu Foundation with the slogan ‘No More Powder Milk’. The chief guest for the occasion was local public representative and Ward Commissioner Md. Humayun Kabir. Community people, especially the pregnant and other women from the Lalbag and Hazaribag areas participated and benefited from the discussion session.
The speakers said that mothers are depending more on the powder milk while the tinned powder milk were found no more safe for the children.The detection of melamine in several renowned powder milk brands has been the most sensational m issue in recent times.
The speakers pointed out that melamine is usually used to make plastic, adhesive, foam or fertilizers. This melamine is mixed with powder milk to increase the nutritional value artificially, though it is never suitable to our human bodies. The powder milk containing melamine damages the kidneys of the children drinking it; as a result the children are exposed to instant death or lifelong kidney problems.
It is essential to take some necessary steps to encourage breast-feeding of children and avoid powder milk. We also need to ensure consumer rights through ensuring proper quality of food items, national adviser of UNIDO Mr. Zahid Hossain said.
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