The
nanoconjugates will be useful for cancer patients suffering from bacterial
infections
A new antibiotic drug-delivery system that improves the
efficacy of drugs thereby reducing the dosage used for treating bacterial
infections has been tested in a lab by researchers at the Indian Institute of
Technology (IIT) Delhi. A peptide, which has not been approved for clinical
use, bound to gold nanoparticles was able to kill E. coli and Salmonella
typhi more efficiently at lower dosages.
“Drug delivery becomes better and the bioavailability
improves when the drug is conjugated [bound] to gold nanoparticles. So reduced
dosage is sufficient to kill the bacteria. Reducing the dosage of antibiotics
used is one of the strategies to reduce the possibility of drug resistance
setting in,” says Dr. Neetu Singh from the Centre for Biomedical Engineering,
IIT Delhi, and one of the corresponding authors of the paper published in the
journal Scientific Reports.
Bioavailability
The peptide in a free form may not be bioavailable as it gets
degraded relatively fast. In a free form, the peptide is also not able to effectively
kill the bacteria by engaging with the bacterial membrane and disrupting it,
while the nanoconjugate fares better on these counts.
The challenge was to arrive at an optimum number of peptides
that are bound to nanoparticles to get the best results. When there are too few
or too many peptides bound to the nanoparticles the antibacterial activity gets
compromised. “There is significant antibacterial activity when about 1000
peptides are bound to a nanoparticle,” says Dr. Singh.
The peptide called sushi-peptide bound to nanoparticles was
able to kill 50% of bacteria at much lower concentration (400 nM) while the
free peptide’s antibacterial activity was not significant at the same
concentration, says Smita Patil from the Centre for Biomedical Engineering, IIT
Delhi and one of the first authors of the paper.
Besides normal cells infected with bacteria, the peptide
bound to nanoparticles will be particularly useful in the case of cancer
patients suffering from bacterial infections. “Rapid metabolism at the cancer
site sucks al nutrients and leads to nutritional deficit in the body. When
chemotherapy is given even the bacteria already present in the body but kept
under check become disease-causing,” says Dr. Pankaj Chaturvedi, cancer
specialist at the Tata Memorial Hospital, Mumbai.
After chemotherapy the immunological response gets damaged as
cells responsible for protecting against bacteria are reduced in number. So the
person becomes vulnerable to infection. “Antibiotics by itself cannot kill all
the bacteria. The inherent immunological response should be able to challenge
the bacteria once antibiotic treatment is completed. Since this does not
happen, the bacteria develop drug resistance,” says Dr. Chaturvedi.
Folate
receptors
Specific receptors called folate receptors are present in
large numbers on the surface of cancer cells. Folic acid added to the
nanoconjugates is recognised by these receptors and help in the binding
process. “Once the nanoconjugates enter the cancer cells they interact with the
bacteria and kill them by disrupting the cell membrane. The nanoconjugates have
40% better antibacterial activity compared with free peptides,” says Rohini
Singh from the Department of Chemical Engineering, IIT Delhi, and one of the
first authors of the paper.
The nanoconjugate is not toxic to cancer cells and targets
only the bacteria.
“We would next like to study if our nanoconjugates can be
used on antibiotic-resistant strains and also understand the fate of gold
nanoparticles used for making the nanoconjugates,” says Dr. Neetu Singh.
Instead of gold nanoparticle, biodegradable polymers can be used. The only
condition is that the peptide should be able to interact with the bacterial
membrane. A few more studies have to be carried out before the nanoconjugate can
be tested on animals.
Source:THE HINDU-6th August, 2017
