One-Pot Synthesis of Affordable Redox-Responsive Drug Delivery System Based on Trithiocyanuric Acid Nanoparticles.

Redox-responsive drug delivery systems present a promising avenue for drug delivery due to their ability to leverage the unique redox environment within tumor cells. In this work, we describe a facile and cost-effective one-pot synthesis method for a redox-responsive delivery system based on novel trithiocyanuric acid (TTCA) nanoparticles (NPs). We conduct a thorough investigation of the impact of various synthesis parameters on the morphology, stability, and loading capacity of these NPs. The great drug delivery potential of the system is further demonstrated in vitro and in vivo by using doxorubicin as a model drug. The developed TTCA-PEG NPs show great drug delivery efficiency with minimal toxicity on their own both in vivo and in vitro. The simplicity of this synthesis, along with the promising characteristics of TTCA-PEG NPs, paves the way for new opportunities in the further development of redox-responsive drug delivery systems based on TTCA.

Proteolytic Resistance Determines Albumin Nanoparticle Drug Delivery Properties and Increases Cathepsin B, D, and G Expression.

Proteolytic activity is pivotal in maintaining cell homeostasis and function. In pathological conditions such as cancer, it covers a key role in tumor cell viability, spreading to distant organs, and response to the treatment. Endosomes represent one of the major sites of cellular proteolytic activity and very often represent the final destination of internalized nanoformulations. However, little information about nanoparticle impact on the biology of these organelles is available even though they represent the major location of drug release. In this work, we generated albumin nanoparticles with a different resistance to proteolysis by finely tuning the amount of cross-linker used to stabilize the carriers. After careful characterization of the particles and measurement of their degradation in proteolytic conditions, we determined a relationship between their sensitivity to proteases and their drug delivery properties. These phenomena were characterized by an overall increase in the expression of cathepsin proteases regardless of the different sensitivity of the particles to proteolytic degradation.