Increasing the accumulation of modular nanotransporters in mouse tumors by attaching polyethylene glycol to these nanotransporters with the possibility of its release into the tumors

Previously, polypeptide constructs – modular nanotransporters (MNT) – were created to deliver biologically active molecules into the nuclei of melanoma cells. In the present work, polyethylene glycol (PEG) molecules were attached to them at the N-terminal cysteine, both with the possibility of their subsequent cleavage at the hydrolysis site of tumor-specific proteases, and without this site (non-detachable PEG). All MNT variants labeled with the radioisotope ¹¹¹In were administered to mice with inoculated Cloudman S91 melanoma. The kinetics of radioactivity distribution in the mouse body was studied using single-photon emission computed tomography. Analysis of the obtained data using a compartmental mathematical model allowed us to establish that the attachment of PEG to MNT increased its lifetime in the blood and significantly increased its accumulation in the tumor. Addition of a PEG detachment site by tumor-specific protease led to a strong retention of this MNT in the tumor. The data obtained can serve as a basis for the creation of new effective antitumor drugs.

modular nanotransporters, melanoma, polyethyleneglycol, single-photon emission computed tomography, tumor-specific proteases, compartment model