Photo-controlled dendrimers for cancer therapy

Abstract

A novel photo-responsive drug delivery system was developed based on polyamidoamine (PAMAM) dendrimers with multiple amino groups on the surface. PAMAM is a suitable drug carrier due to its small size and the hydrophobic core. However, the high surface charge of PAMAM shortens its circulation time in the blood and induces cell death from destructive autophagy, leading to severe side effects. In the designed drug delivery system, polyethylene glycol (PEG) is conjugated on the PAMAM surface via a photo-liable coumarin derivate. The PEG surrounding PAMAM surface protects PAMAM during circulation and decreases the undesired accumulation in the healthy tissues. Upon light irradiation at tumor sites, PEG is cleaved from the surface, reducing the size of PAMAM and exposing amino groups. This process accelerates the release of drugs loaded in the PAMAM. Meanwhile, the naked PAMAM promotes cellular uptake and induces destructive autophagy, efficiently killing cancer cells. In summary, this photo-responsive drug delivery system can achieve controlled drug release and high efficiency of killing cancer cells with destructive autophagy and chemotherapy.