Intracellular drug delivery, or taking a therapeutic agent into the interior of cells, where they can be more effective, holds great promise for the treatment of various diseases, particularly cancer and genetic disorders. However, taking a drug inside a cell is not easy; several challenges need to be overcome.
For example, the drugs should attack only the affected cells and not healthy ones, should remain stable once inside, and should not elicit an immune response. The biggest challenge is in getting past the cell wall.
Scientists are constantly looking for ways to get therapeutic agents (drugs, enzymes, peptides, small molecules, genes, and so on) past the cell membrane.
In this direction, two recent advancements in Indian laboratories have come to light.
One is through a multi-institution research (IIT-Madras, Toyohashi University of Technology-Japan, IISER-Tirupati, and Christian Medical College-Vellore), which uncovered that ‘nano-burflower shaped gold nanoparticles’ can improve the efficiency of intracellular delivery.. This is particularly useful in the treatment of cancer.
Delivery of biomolecules into cells is of great importance as this can be used for improved drug delivery, cell targeting, and cell and gene therapy. The means for introducing biomolecules into cells include viral and chemical methods; and physical methods such as magnetoporation, electroporation, and photoporation. Of these, photoporation or optoporation is the least invasive and least damaging to cells.
Photoporation involves interaction of light and matter to disrupt the cell membrane and deliver drugs inside live cells. It can be used along with microfluidics (manipulating small amounts of fluids) to deliver biomolecules into the cell with high efficiency and cell viability.
“Infrared pulsed laser irradiation on nano-burflower gold nanoparticles resulted to enhance a higher electromagnetic field in the tips or spikes of the nano-burflower nanoparticles in comparison with normal spherical gold nanoparticles. As a result, cell membranes can deform easily and create nanopores and deliver drugs from outside to inside of the live cells,” a note from the researchers says.
This is for the first time that the benefits of droplet microfluidics in nano-burflower gold nanoparticles synthesis have been demonstrated for intracellular delivery of small to very large therapeutic molecules using infrared light pulses.
Viable technique
Dr Tuhin Subhra Santra, Associate Professor, Department of Engineering Design, IIT-Madras, says, “This technique can achieve high delivery efficiency and cell viability using any type of genes as well as very large enzyme delivery into live cells, which is not possible using any other methods.”
“This research has translational potential in healthcare technology, including development of therapeutic strategies against various types of cancer and gene therapy,” says Prof Nitish R Mahapatra, Department of Biotechnology, IIT-Madras.
Use of Covid-19 virus
In another research, scientists at the Bose Institute, Kolkata, have figured out a new way to create hydrogels using tiny protein fragments of just five amino acids from the SARS-CoV-1 virus, which could help improve targeted drug delivery and reduce side effects. Hydrogels (gels in which the liquid has been sucked out, leaving only the solid shell) are known to be suitable for drug delivery because of their swelling, mechanical strength and biocompatibility.
Short peptide-based hydrogels hold potential for many applications. However, researchers have found their gelation difficult to control. Minor changes in the peptide sequence can significantly influence the self-assembly mechanism and, thereby, the gelation propensity.
Following the use of SARS-CoV-E protein in the assembly and release of the virus, researchers deduced it may have inherent self-assembling properties that can contribute to the development of hydrogels.
Prof Anirban Bhunia of Bose Institute and his collaborators from the Indian Institute of Science, Bengaluru; University of Texas Rio Grande Valley, USA; and Indian Association for the Cultivation of Science, Kolkata, showed that by rearranging just five amino acids of the SARS-CoV-1 virus, one can make gels from pentapeptides with unique properties. Some become gel when heated, others at room temperature.
“This unique discovery could lead to significant medical advancements like customisable hydrogels that can improve targeted drug delivery, enhancing treatment efficacy while reducing side effects,” says a Bose Institute press release.
These materials could revolutionise tissue engineering, potentially aiding in organ regeneration, it says.
