Organic Stealth Nanoparticles for Highly Effective <i>in Vivo</i> Near-Infrared Photothermal Therapy of Cancer

Abstract

In recent years, a wide range of near-infrared (NIR) light absorbing nanomaterials, mostly inorganic ones, have been developed for photothermal therapy (PTT) of cancer. In this work, we develop a novel organic PTT agent based on poly-(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate) (PEDOT:PSS), a conductive polymer mixture with strong NIR absorbance, for <i>in vivo</i> photothermal treatment of cancer. After being layer-by-layer coated with charged polymers and then conjugated with branched polyethylene glycol (PEG), the obtained PEDOT:PSS-PEG nanoparticles are highly stable in the physiological environment and exhibit a stealth-like behavior after intravenous injection with a long blood circulation half-life. As a result, an extremely high <i>in vivo</i> tumor uptake of PEDOT:PSS-PEG attributed to the tumor-enhanced permeability and retention effect is observed. We further use PEDOT:PSS-PEG as a PTT agent for <i>in vivo</i> cancer treatment and realize excellent therapeutic efficacy in a mouse tumor model under NIR light irradiation at a low laser power density. Comprehensive blood tests and careful histological examination reveal no apparent toxicity of PEDOT:PSS-PEG to mice at our treated dose within 40 days. To our best knowledge, this work is the first to use systemically administrated conductive polymer nanoparticles for highly effective <i>in vivo</i> PTT treatment in animals and encourages further explorations of those organic nanomaterials for cancer theranostic applications