Rational design of ibuprofen-based redox-responsive anti-cancer polymeric drug delivery systems

An increasing number of studies have demonstrated that inflammation has a close correlation with multiple stages of tumor development, including tumor initiation, promotion, and migration. Cyclooxygenase-2 (COX-2), which is overexpressed in inflammation, has also been found to be overexpressed in several types of cancer. Some anti-inflammatory drugs have been shown to have potential effects on the inhibition of tumor pathogenesis and development. Among them, non-steroidal anti-inflammatory drugs (NSAIDs) play a role by inhibiting the overexpression of COX-2 with low price and few side effects. In this work, ibuprofen was linked to an amphiphilic polymer mPEG-PLA via disulfide bond to form a polymeric prodrug molecule with reductive sensitivity. The amphiphilic molecule can self-assemble into nanoparticles in an aqueous solution and encapsulate hydrophobic drug, doxorubicin, into the core. Electrostatic potential analysis and weak interaction analysis showed different weak interactions, including hydrogen bonds and pi-pi stackings, are the driving force of the formation of the complex system between doxorubicin and polymeric prodrug molecules. These quantitative calculations were helpful to understand the formation mechanism of prodrug polymeric carriers. Characterization methods such as TEM and DLS proved that mPEG-PLA-s-IHE/DOX (PDC/DOX) micelles had an excellent uniform nanostructure, and in vitro drug release experiments showed superior sustained-release and reductive environment-dependent release of this drug. More importantly, in vitro cytotoxicity and cell uptake studies showed that the PDC /DOX micelles induced apoptosis of A549 lung cancer cell lines. This study demonstrates the advantage of combining NSAIDs with chemotherapy agents in the treatment of lung cancer, which provides a feasible and novel polymer delivery system, and a reasonable explanation of formation mechanism. [GRAPHICS] .

Automated summary

An increasing number of studies have shown the correlation between inflammation and tumor development. This study demonstrates the advantage of combining anti-inflammatory drugs with chemotherapy agents in the treatment of lung cancer, providing a feasible and novel polymer delivery system.