Laser-activatible PLGA microparticles for image-guided cancer therapy in vivo

Abstract

Poly(lactide-co-glycolic acid) (PLGA) particles are biocompatible and biodegradable, and can be used as a carrier for various chemotherapeutic drugs, imaging agents and targeting moieties. Micrometer-sized PLGA particles were synthesized with gold nanoparticles and DiI dye within the PLGA shell, and perfluorohexane liquid (PFH) in the core. Upon laser irradiation, the PLGA shell absorbs the laser energy, activating the liquid core (liquid conversion to gas). The rapidly expanding gas is expelled from the particle, resulting in a microbubble; this violent process can cause damage to cells and tissue. Studies using cell cultures show that PLGA particles phagocytosed by single cells are consistently vaporized by laser energies of 90 mJ cm-2, resulting in cell destruction. Rabbits with metastasized squamous carcinoma in the lymph nodes are then used to evaluate the anti-cancer effects of these particles in the lymph nodes. After percutaneous injection of the particles and upon laser irradiation, through the process of optical droplet vaporization, ultrasound imaging shows a significant increase in contrast in comparison to the control. Histology and electron microscopy confirm damage with disrupted cells throughout the lymph nodes, which slows the tumor growth rate. This study shows that PLGA particles containing PFC liquids can be used as theranostic agents in vivo.