Polyethylenimine modified with 2,3-dimethylmaleic anhydride potentiates the antitumor efficacy of conventional chemotherapy.

Polyethylenimine modified with 2,3-dimethylmaleic anhydride potentiates the antitumor efficacy of conventional chemotherapy. Mater Sci Eng C Mater Biol Appl. 2019 Sep;102:558-568 Authors: Huang X, Cao J, Zhang Y, Liu T, Yan H Abstract Conventional chemotherapy is a standard care for many cancers at present. However, their severe dose-dependent side effects are the major impediment for successful cancer therapy. Herein nanoparticles were used as a potentiator to enhance the uptake of free chemotherapeutic agents by cancer cells during chemotherapy. A pH-sensitive β-carboxylate amide group-containing polymer, bPEI-DMA, was obtained by a one-step chemical reaction of commercially available branched polyethyleneimine with 2,3-dimethylmaleic anhydride. The obtained single-macromolecule nanoparticles with a size of 6.4 nm possessed zwitterions and a slight net negative charge at neutral pH, and thereby showed low cytotoxicity. Incubation of MCF-7 cells with bPEI-DMA at tumor acidic pHs led to leakage of lactate dehydrogenase from the cells. Sequential incubation of bPEI-DMA and doxorubicin with MCF-7 cells at tumor acidic pHs caused enhanced uptake of doxorubicin by the cells. These results can be attributed to the tumor pH-triggered positive charge generation on the nanoparticles due to the hydrolysis of the β-carboxylate amide groups, and subsequently the positive charge caused an increase in cell membrane permeability. Sequential in...
Source: Appl Human Sci - Category: Physiology Authors: Tags: Mater Sci Eng C Mater Biol Appl Source Type: research