Mechanical properties of nanoparticles affecting interactions with tumor cells

Controlling the interaction of drug delivery systems (DDS) with biological tissues is critical for the success of therapies. Specifically in cancer, due to the high density of the tumors, tissue penetration of DDS is critical... [ view full abstract ]

Controlling the interaction of drug delivery systems (DDS) with biological tissues is critical for the success of therapies. Specifically in cancer, due to the high density of the tumors, tissue penetration of DDS is critical and may be challenging. We showed that polymer nanoparticles can be used efficiently to deliver small molecule drugs into cancer cells and tissues. In our recent work we study the effect of mechanical cues of drug vehicle on their interactions with tumor cells and tissue-like 3D structures ex-vivo. Using polymer micelles we compared flexible "Wet Polymer Micelles" (WPM) to semi-solid "Solidified Polymer Micelles" (SPMs) for their physiochemical properties and their interactions with cancer cells. The composition of the polymer micelles, both flexible and rigid remained the same while the only difference was their mechanical properties. For that we have performed detailed characterization of SPM compared to WPM, including examinations of particle size, stability, drug release kinetics and cell transcytosis, in melanoma A-375 cells. Cell uptake measurements were done using FACS and microscopy imaging, showing enhanced abilities of SPMs to penetrate cells and tissues. A simple physical model is presented that well agrees with the experiments and provides insight about the role of particle rigidity in the engulfment mechanism. We conclude that particle rigidity can enhances cellular uptake and tissue penetration and that mechanical properties of DDS be used as a selective principle for drug uptake. We also introduced SPMs as a promising and effective, highly permeable DDS. Our findings can be important in future rational design of DDS for particle adjustment to specific tissues and pathology, and for personalized Nanomedicine.