Superbug and quantum dot
Two IIT-Delhi alumni use light to persuade invisible bits of semiconductor material to kill drug-resistant bacteria
It
challenges the limits of physical law, the ability of the scientist and
the imagination of the ignorant. The nanoscale is a challenging
frontier where atoms and molecules, the building blocks of everything,
are manipulated. The tools are infinitesimally small, the problems
addressed, among Earth’s biggest.
The problem in question is the rise of super-bacteria resistant to the latest antibiotics, the last line of medical defence against various infections, cancer and HIV. The rampant, indiscriminate administration of common antibiotics—penicillin is a prime example—has allowed bacteria such as Salmonella, Staphylococcus and E. coli the ability to shuffle their genes and defeat these drugs. For humanity, it’s always been a one-step-ahead-many-steps-back battle in the war against the superbugs, which use evolutionary abilities to overwhelm medical advances.
This week, Prashant Nagpal, Anushree Chatterjee (both are PhDs and alumni of Indian Institute of Technology, Delhi) and their colleagues at the University of Colorado-Boulder took us a step ahead, as they revealed the development of a light-activated superbug-killing nanoparticle some 20,000 times smaller than the width of a human hair. The nanoparticles, known as quantum dots, are each one million times smaller than a millimetre, and they killed nine of 10 drug-resistant bacterial cells grown in a laboratory culture and resistant to all known antibiotics, according to a paper published this week in the journal Nature Materials. The quantum dots were used in tiny concentrations, about a thousand times smaller than current drugs in a pill, Nagpal, a recipient of several awards, told me in an email interview. The development of the quantum-dot nanoparticles required much interdisciplinary research, stretching into biology, chemistry and electronics.
As the superbugs evolve, adapt and fight back, the quantum dots can be tuned, or customised, with an atom added or subtracted to create a new material, property or therapy, while using data from related clinical trials or drugs, said Nagpal, an assistant professor and senior author of the study. With Chatterjee (also an assistant professor and senior author), Nagpal has co-founded PRAAN (life in Hindi) Biosciences, a start-up that uses a separate discovery from their laboratories: A single DNA molecule to sequence genetic profiles to diagnose and treat the infections that drug-resistant bacteria cause. The duo has also filed a patent for the quantum dot.
Antibiotic-resistant bacteria infect about two million people and kill at least 23,000 people in the US each year. There is no comparative data for India, but the country is the world’s largest consumer of antibiotics and has emerged as a leading hotbed of untreatable bacterial infections, their threat doubling over five years, my colleague Charu Bahri reported in November.
Gold and silver nanoparticles—among other materials—have previously been used to attack superbug infections, with varying degrees of success. Their main drawback is the damage to surrounding cells. The quantum dots, fashioned in Nagpal and Chatterjee’s laboratory in water from several semiconductor materials—used in solar panels or mobile phones—show different effects on bacteria. For instance, cadmium telluride nanoparticles have a therapeutic effect against drug-resistant bacteria; similar-sized copper indium sulfide particles help good bacteria grow, said Nagpal, useful for future mass production. The quantum dots are benign in darkness. Much as in any semiconductor, light—a room lamp or sunlight will do—excites electrical charges in the quantum dots and sparks a chemical reaction. Varying the wavelength of light, or size, composition and surface of the dots, allows selective killing of drug-resistant bacteria, without harming host human cells.
“This means, if successful in further clinical trials, we can simply administer these dots to patients with infections and it can cure the infection without potential effects (or side-effects) for healthy host cells,” said Nagpal, who with Chatterjee and other colleagues is currently conducting pre-clinical trials using animals. “We have tested our therapy, as a blind trial, on five-worst patient isolates (actual clinical samples from the University of Colorado Medical Campus), and it has been effective against each and every one of them!”
They envisage three modes of quantum-dot therapy and drug administration. First, for topical infections caused by wounds or cuts, where a sticky adhesive patch coated with nanoparticles will need to be illuminated with light to begin treatment. Second, for systemic infections, which will need the drug to be injected or administered intravenously. “Based on results we see with clinical studies, if the nanoparticles are dispersed evenly, will be effective for patients exposed to a well-lit room or photo-therapy room,” Nagpal said. Third, as a disinfectant—for instance, on hospital surfaces or instruments—in a well-lit or specially lighted room.
Nagpal and Chatterjee now require funding from government or private donors for clinical trials, the final and most challenging proving grounds that take any therapy from laboratory to market—and determine if the quantum dot could be the next small, big thing.
The problem in question is the rise of super-bacteria resistant to the latest antibiotics, the last line of medical defence against various infections, cancer and HIV. The rampant, indiscriminate administration of common antibiotics—penicillin is a prime example—has allowed bacteria such as Salmonella, Staphylococcus and E. coli the ability to shuffle their genes and defeat these drugs. For humanity, it’s always been a one-step-ahead-many-steps-back battle in the war against the superbugs, which use evolutionary abilities to overwhelm medical advances.
This week, Prashant Nagpal, Anushree Chatterjee (both are PhDs and alumni of Indian Institute of Technology, Delhi) and their colleagues at the University of Colorado-Boulder took us a step ahead, as they revealed the development of a light-activated superbug-killing nanoparticle some 20,000 times smaller than the width of a human hair. The nanoparticles, known as quantum dots, are each one million times smaller than a millimetre, and they killed nine of 10 drug-resistant bacterial cells grown in a laboratory culture and resistant to all known antibiotics, according to a paper published this week in the journal Nature Materials. The quantum dots were used in tiny concentrations, about a thousand times smaller than current drugs in a pill, Nagpal, a recipient of several awards, told me in an email interview. The development of the quantum-dot nanoparticles required much interdisciplinary research, stretching into biology, chemistry and electronics.
As the superbugs evolve, adapt and fight back, the quantum dots can be tuned, or customised, with an atom added or subtracted to create a new material, property or therapy, while using data from related clinical trials or drugs, said Nagpal, an assistant professor and senior author of the study. With Chatterjee (also an assistant professor and senior author), Nagpal has co-founded PRAAN (life in Hindi) Biosciences, a start-up that uses a separate discovery from their laboratories: A single DNA molecule to sequence genetic profiles to diagnose and treat the infections that drug-resistant bacteria cause. The duo has also filed a patent for the quantum dot.
Antibiotic-resistant bacteria infect about two million people and kill at least 23,000 people in the US each year. There is no comparative data for India, but the country is the world’s largest consumer of antibiotics and has emerged as a leading hotbed of untreatable bacterial infections, their threat doubling over five years, my colleague Charu Bahri reported in November.
Gold and silver nanoparticles—among other materials—have previously been used to attack superbug infections, with varying degrees of success. Their main drawback is the damage to surrounding cells. The quantum dots, fashioned in Nagpal and Chatterjee’s laboratory in water from several semiconductor materials—used in solar panels or mobile phones—show different effects on bacteria. For instance, cadmium telluride nanoparticles have a therapeutic effect against drug-resistant bacteria; similar-sized copper indium sulfide particles help good bacteria grow, said Nagpal, useful for future mass production. The quantum dots are benign in darkness. Much as in any semiconductor, light—a room lamp or sunlight will do—excites electrical charges in the quantum dots and sparks a chemical reaction. Varying the wavelength of light, or size, composition and surface of the dots, allows selective killing of drug-resistant bacteria, without harming host human cells.
“This means, if successful in further clinical trials, we can simply administer these dots to patients with infections and it can cure the infection without potential effects (or side-effects) for healthy host cells,” said Nagpal, who with Chatterjee and other colleagues is currently conducting pre-clinical trials using animals. “We have tested our therapy, as a blind trial, on five-worst patient isolates (actual clinical samples from the University of Colorado Medical Campus), and it has been effective against each and every one of them!”
They envisage three modes of quantum-dot therapy and drug administration. First, for topical infections caused by wounds or cuts, where a sticky adhesive patch coated with nanoparticles will need to be illuminated with light to begin treatment. Second, for systemic infections, which will need the drug to be injected or administered intravenously. “Based on results we see with clinical studies, if the nanoparticles are dispersed evenly, will be effective for patients exposed to a well-lit room or photo-therapy room,” Nagpal said. Third, as a disinfectant—for instance, on hospital surfaces or instruments—in a well-lit or specially lighted room.
Nagpal and Chatterjee now require funding from government or private donors for clinical trials, the final and most challenging proving grounds that take any therapy from laboratory to market—and determine if the quantum dot could be the next small, big thing.
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