Diseased cells such as metastatic cancer cells have markedly different mechanical properties that can be used to improve targeted drug uptake, according to a team of researchers at Penn State.
Many labs around the world are developing nanoparticle-based drug delivery systems to selectively target tumors. They rely on a key-and-lock system in which protein keys on the surface of the nanoparticle click into the locks of a highly expressed protein on the surface of the cancer cell. The cell membrane then wraps around the nanoparticle and ingests it. If enough of the nanoparticles and their drug cargo is ingested, the cancer cell will die.
The adhesive force of the lock and key is what drives the nanoparticle into the cell, says Sulin Zhang, professor of engineering science and mechanics. “It is almost universal that whenever there is a driving force for a process, there always is a resistive force. Here, the driving force is biochemical – the protein-protein interaction.”
The resistive force is mechanical, the energy cost of the membrane wrapping around the nanoparticle. Until now, bioengineers only considered the driving force and designed nanoparticles to optimize the chemical interactions, a targeting strategy called “chemotargeting.” Zhang believes they should also take into account the mechanics of the cells to design nanoparticles to achieve enhanced targeting, which forms a new targeting strategy called “mechanotargeting.”

Image Credit:  Zhang lab/vecteezy.com

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