Targeting cell surface glycan for effective therapeutic output

Membranes are the gateway for many natural events inside the cell. Hence, membrane constituents such as lipid, protein and glycan have emerged as an alternative target for drug development. The development of membrane targeted therapy for infectious diseases and cancerous condition is made possible by the fact the there are fundamental difference between the membrane composition of microbes and humans. Similarly, the cell membrane glycan patterns of normal and cancer cells are different. Lectins are sugar binding proteins present in all form of life, which has the ability to recognize specific glycans. Owing to the preferential interaction of lectin with cell surface glycan, we are interested in screening for lectins from widely reachable source to develop membrane glycan targeting drug delivery vehicles. Jacalin, a galactose binding lectin isolated from the seeds of jackfruit have already been study for T-antigen specificity. We exploited the T-antigen specificity to distinguish cancerous and normal cells through optical imaging using jacalin-cadmium sulphide quantum dots. Additionally, jacalin in complex with anticancer molecule minimize the drug requirement without compromising the anticancer activity. Our current work focus on understanding the lectin-drug interaction, lectin conjugates interaction with membranes and drug release using biochemical and biophysical approaches.

The disposition of drug in biological system may get altered by complex biological fluids; especially protein binding to drugs influences their activity. Can drugs carried with lectins overcome the interference from biological fluids? Our studies showed the antimicrobial nanoparticles loaded into lectins exert excellent activity against pathogenic bacteria at multi-fold lower concentration than nanoparticles alone. Also, lectin conjugates mitigate the interference from serum proteins. Testing in animal model reveals that lectin conjugates elicit adaptive immunity to combat microbial reinfection. Besides antimicrobial, lectin conjugates also exhibit true antifilm biofilm effect. This makes lectin as an interesting candidate for planning future therapeutic strategies against multi-drug resistant bacteria. Hence, we are interested in determining the exact role of lectins in antimicrobial therapeutics.