Development of ROS‐responsive amino acid‐based poly(ester amide) nanoparticle for anticancer drug delivery

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Abstract
Reactive oxygen species (ROS) play an important role in cellular metabolism and many oxidative stress related diseases. Oxidative stress results from toxic effects of ROS and plays a critical role in the pathogenesis of a variety of diseases like cancers and many important biological processes. It is known that the unique feature of high intracellular ROS level in cancer cells can be considered as target and utilized as a useful cancer‐related stimulus to mediate intracellular drug delivery. Therefore, biomaterials responsive to excess level of ROS are of great importance in biomedical applications. In this study, a novel ROS‐responsive polymer based on L‐methionine poly(ester amide) (Met‐PEA‐PEG) was designed, synthesized, characterized and self‐assembled into nano‐micellar‐type nanoparticles (NP). The Met‐PEA‐PEG NP exhibited responsiveness to an oxidative environment. The size and morphology of the nanoparticle changed rapidly in the presence of H2O2. The Nile Red dye was loaded into the Met‐PEA‐PEG NP to demonstrate a H2O2 concentration induced time‐dependent release behavior. The Met‐PEA‐PEG NP was sensitive to high intracellular ROS level of PC3 prostate cancer cells. Furthermore, the Met‐PEA‐PEG NP was investigated as a carrier of a Chinese medicine‐based anticancer component, gambogic acid (GA). Compared to free GA, the GA‐loaded nanocomplex (GA‐NP) showed enhanced cytotoxicity toward PC3 and HeLa cells. The GA‐NP also induced a higher level of apoptosis and mitochondrial depolarization in PC3 cells than free GA. The Met‐PEA‐PEG NP improved the therapeutic effect of GA and may serve as a potential carrier for anticancer drug delivery.

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