UC San Diego

The majority of small-molecule therapeutics are hydrophobic, leading to low bioavailability and therapeutic efficiency, which limits their biomedical applications. A promising strategy to address the hydrophobicity of these molecules is to incorporate them into nanocarriers. However, this approach faces challenges, including low mass loading of hydrophobic molecules, poor colloidal stability, and limited biodegradability of nanocarriers. Porous silicon nanoparticles, due to their biocompatibility, high biodegradation rate, and high surface area, offer a promising platform for delivering hydrophobic small-molecule therapeutics. Here, we have modified the surface of porous silicon nanoparticles with in-situ precipitated calcium silicate, hydrophobic hydrocarbon groups, or amphiphilic hydrocarbon groups to enhance the incorporation of small-molecule therapeutics. Additionally, lipid or non-ionic surfactant coatings were applied to improve the colloidal stability of the drug-loaded porous silicon nanoparticles. With these surface modifications, porous silicon nanoparticles demonstrate high mass loading of small-molecule therapeutics, enhanced colloidal stability, favorable biodegradation rates, and/or improved therapeutic efficiencies, highlighting their potential for drug delivery and photodynamic therapy.