Synthesis and cytotoxicity evaluation of gemcitabine-tobacco mosaic virus conjugates

Gemcitabine is one of the nucleoside analogue drugs that acts against a wide range of solid tumors such as pancreatic, non-small lung, breast, and ovarian cancers. Unfortunately, gemcitabine possesses rapid body clearance that limits its efficacy. This drawback is due to kidney excretion and metabolism by plasmatic enzyme cytidine-deaminase, which yields an inactive metabolite. Plant virus nanoparticles are one of the biggest groups of natural nanoparticles, which are less likely to interact with mammalian system to make adverse effects and can be used in drug delivery. In this study, chemical conjugation of gemcitabine and Tobacco Mosaic Virus (TMV); as one of the mostly used plant viruses, has been investigated through the creation of amide bond and the percentage of conjugation was calculated using UV spectroscopy. The drug release from conjugate was pH dependent and, at acidic pH, the drug release was almost complete. The hemolysis percentage caused by the virus and the conjugate was also proved to be very small. Cytotoxicity studies at 24 and 48-h showed that there was no significant difference between the free drug and drug conjugate in HepG2 and MCF7 cell lines, but the results of the toxicity study were better on HepG2 cell line. Also in both cell lines, the observed cytotoxicity of the conjugate was more acceptable after 48 h which is due to enough time for drug release. It is expected that these viral nanoparticles make better in vivo drug delivery, pharmacokinetics improvement and reduced dose related toxicity of chemotherapeutic agents.

Automated summary

Gemcitabine, a nucleoside analogue drug, has limitations due to rapid body clearance, but chemical conjugation with Tobacco Mosaic Virus shows potential for drug delivery with minimal toxicity. In vitro studies suggest improved cytotoxicity and drug release from the conjugate, indicating potential for better pharmacokinetics and reduced toxicity in vivo.