Redox-responsive liposomes aimed at nitroreductase for contents release

Here, we report a novel stimuli-responsive N-DOPE liposome where the redox-active 4-nitrobenzyl formate head group of liposomes would respond with respect to the presence of nitroreductase present in the environment of tumor tissues to release the payload. Our main emphasis is related to the construction of redox-sensitive liposomes that would function as the liposomal drug carriers to malignant tumors. Our N-DOPE liposome contains a nitro group (-NO₂) in the modified lipid, and we expect the reduction of the nitro group (-NO₂) to amine (-NH₂) would release the calcein (drug) through the 1,6 elimination as per our hypothesis. But we found no release after waiting for almost 20 hours with the use of Na₂S₂O₄, nitroreductase (NTR) and changes of different external environmental conditions, <i>i.e.</i> temperature, aerobic and anaerobic, etc. due to the formation of an azo (R-N = N-R) bond that stops the complete reduction of (-NO₂) all the way down to form amine (-NH₂) to stop releasing the payloads. However, adding an organic group containing nitro during the reduction process with the Na₂S₂O₄ resulted in a 45% release of liposomal content. A detailed study &amp; explanation of the formation of azo bond in our N-DOPE liposome has been shown in a stepwise manner in through various spectroscopic methods, and we have discussed future directions.