Click-Engineered, Bioresponsive, and Versatile Particle-Protein-Dye System

We present a multifunctional polymer based nanoparticle platform for personalized nanotheranostic applications, which include photodynamic therapy and active targeting. In this system, poly(propargyl acrylate) (PA) particles were surface-modified with organic ligands and fluorophores (the payload) through an environmentally-sensitive linker. An azide modified bovine serum albumin (azBSA) was employed as the linker. This system prevents opsonization and, upon digestion, releases the payload. Attachment of the emitting payload to the particle through azide-modified bovine serum albumin (BSA) quenches emission, which can be again activated with digestion of the azBSA. The emission "turn-on" at a specific location will increase the signal-to-noise ratio. By utilizing human head and neck squamous carcinoma cells (UMSCC22A), photodynamic therapy studies with these particles gave promising reductions in cell growth. Additionally, the particle-protein-dye system is versatile as different fluorophores (such as silicon phthalocyanine or cyanine 3) can be attached to the protein and the same activation/deactivation behavior is observed. Active targeting can be employed to enhance the concentration of the payload in the designated tumor. Human lung carcinoma cells (A549) were utilized in toxicity studies where PA-azBSA particles were modified with a Survivin targeting ligand and indicated an enhanced cell death with the modified particles relative to the "free" Survivin targeting ligand.