A simple, robust and scalable route to prepare sub-50 nm soft PDMS nanoparticles for intracellular delivery of anticancer drugs

Abstract Soft nanoparticles (NPs) have recently emerged as a promising material for intracellular drug delivery. In this regard, NPs derived from polydimethylsiloxane (PDMS), an FDA approved polymer can be a suitable alternative to conventional soft NPs due to their intrinsic organelle targeting ability. However, the available synthesis methods of PDMS NPs are complicated or require inorganic fillers, forming composite NPs and compromising their native softness. Herein, for the first time, we present a simple, robust and scalable strategy for preparation of virgin sub-50 nm PDMS NPs at room temperature. The NPs are soft in nature, hydrophobic and about 30 nm in size. They are stable in physiological medium for two months and biocompatible. The NPs have been successful in delivering anticancer drug doxorubicin to mitochondria and nucleus of cervical and breast cancer cells with more than four-fold decrease in IC50 value of doxorubicin as compared to its free form. Furthermore, evaluation of cytotoxicity in reactive oxygen species detection, DNA fragmentation, apoptosis-associated gene expression and tumor spheroid growth inhibition demonstrate the PDMS NPs to be an excellent candidate for delivery of anticancer drugs in mitochondria and nucleus of cancer cells.