Exploring paclitaxel-loaded adenosine-conjugated PEGylated PLGA nanoparticles for targeting triple-negative breast cancer

In present investigation, we developed paclitaxel (PTX)-loaded adenosine (ADN)-conjugated PLGA nanoparticles for combating triple-negative breast cancer (TNBC), where ADN acts as a substrate for adenosine receptors (AR) that are overexpressed in TNBC. Using synthesized PLGA-PEG-ADN, PTX-loaded nanoparticles (PTX ADN-PEG-PLGA NPs) were prepared via emulsion diffusion evaporation process that rendered particles of size 135 +/- 12 nm, PDI of 0.119 +/- 0.03, and entrapment-efficiency of 79.26 +/- 2.52%. The NPs showed higher %cumulative release at pH 5.5 over 7.4 with Higuchi release kinetics. The PTX ADN-PEG-PLGA NPs showed similar to 4.87-and 5.22-fold decrease in %hemolysis in comparison to free PTX and Intaxel (R), indicating their hemocompatible nature. The ADN modification assisted cytoplasmic internalization of particles via AR-mediated endocytosis that resulted in similar to 3.77-and 3.51-fold reduction in IC50 and showed apoptosis index of 0.93 and 1.18 in MDA-MB-231 and 4T1 cells respectively. The pharmacokinetic profile of ADN-PEG-PLGA NPs revealed higher AUC and t1/2 than Intaxel (R) and Nanoxel (R) pharmacodynamic activity showed similar to 18.90-fold lower %tumor burden than control. The kidney and liver function biomarkers showed insignificant change in the levels, when treated with PTX ADN-PEG-PLGA NPs and exhibited no histological alterations in the liver, spleen, and kidney. Overall, the optimized particles were found to be biocompatible with improved anti-TNBC activity.

Automated summary

In this study, PTX-loaded adenosine-conjugated PLGA nanoparticles were developed for treating TNBC. The nanoparticles showed a small size, high entrapment efficiency, and release at a lower pH. They also exhibited lower hemolysis and improved cellular uptake and anti-TNBC activity compared to free PTX. The nanoparticles had a favorable pharmacokinetic profile and reduced tumor burden without causing significant changes in kidney and liver function biomarkers or histological alterations. Overall, the optimized nanoparticles showed biocompatibility and enhanced anti-TNBC activity.