Stable sub-100 nm PDMS nanoparticles as an intracellular drug delivery vehicle

For the past few decades, polydimethylsiloxane (PDMS) elastomer has been used in plethora of biomedical applications. However, PDMS has not much been explored for intracellular drug delivery since the preparation of sub-100 nm particles, preferred for such kind of applications is extremely difficult owing to its innate nature to form a film. In this work, we have performed molecular dynamics (MD) simulation for developing a strategy to restrict the inherent film-forming tendency of PDMS for obtaining stable sub-100 nm PDMS nanoparticles. MD simulation results suggest that introduction of hydroxyl groups on the surface of PDMS improves its stability in the form of nanoparticles. Based on the MD simulation results, for the first time, sub-100 nm PDMS nanoparticles are prepared via in situ surface modification of PDMS with sodium hydroxide inside nanoemulsion droplets. The synthesized nanoparticles are 30-40 nm in size, extremely soft in nature, moderately hydrophobic and stable in phosphate buffered saline. In vitro results demonstrate the synthesized PDMS nanoparticles to possess excellent biocompatibility and an intrinsic capability of selective localization in mitochondria of cancer cells. Furthermore, efficient mitochondrial delivery of anticancer drug doxorubicin through PDMS nanoparticles advocates for their suitability as a potential candidate for developing advanced nanomedicine.