Silk Nanoparticle Synthesis: Tuning Size, Dispersity, and Surface Chemistry for Drug Delivery

Protein-based nanoparticles have gained interest for traversing different biological (e.g., systemic or microenvironmental, etc.) barriers and enabling targeted drug delivery. Silk protein-based nanoparticles are useful and versatile drug delivery systems for sustained and controlled release due to their biocompatibility, biodegradability, accessible chemistries, and ability to stabilize different drugs and other biomolecules. In the present study, silk nanoparticles (SNPs) were engineered using a nanoprecipitation technique with tight control over size (∼45–250 nm diameter) and low polydispersity index by altering variables including stirring speed, reaction bath temperature, silk molecular weight (MW), and silk concentration. Of these variables, stir speed was the most significant contributor toward particle size control. SNPs with positive or negative surface charges and decoration of SNPs with surface antigens were also demonstrated. New mechanistic insights into control of SNP size, cellular uptake using glioblastoma as a model, surface characteristics, and the entrapment of a small-molecule drug (doxorubicin) within the particles were addressed. These insights expand the potential utility of SNPs for medical, environmental, and food applications.