Design and Synthesis of New PEGylated Polydopamine-Based Nanoconstructs Bearing ROS-Responsive Linkers and a Photosensitizer for Bimodal Photothermal and Photodynamic Therapies against Cancer.

Abstract

Polydopamine (PDA) nanoparticles (NPs) have recently acquired considerable attention for the development of nanoplatforms with multifunctional properties including photothermal (PTT) and photodynamic (PDT) activities. In addition to their high PTT performance, they can be easily conjugated to different types of photosensitizers (PSs) to acquire PDT activity. However, because of PDA free-radical scavenging properties, grafting the PSs directly to PDA surfaces may lead to an inefficient PDT outcome. Thus, the present work aims at synthesizing and characterizing a new PEGylated PDA-based nanoplatform with bifunctional PTT and PDT properties, which allows bimodal cancer therapy with the possibility to release the PS on demand in a spatiotemporal fashion. To do so, PDA NPs with a well-defined size and shape were prepared by the auto-oxidative self-polymerization process of dopamine hydrochloride in mild alkaline solution. The impact of the size on the PTT conversion efficiency was then determined. This allowed us to choose the optimal PDA NP size for PTT applications. Next, PDA NPs were decorated with SH-PEG polymers that bear at their extremity a thioketal reactive oxygen species-cleavable linker coupled to trisulfonated-tetraphenylporphyrin (TPPS3) chosen as a hydrophilic PS. The grafting efficiency of PS-conjugated PEG on PDA was demonstrated in situ using a quartz crystal microbalance with dissipation monitoring. In addition, the photoinduced release of the PS was demonstrated by 1H NMR. Finally, PTT/PDT bimodal therapy was assessed in vitro on human squamous esophageal cells by illuminating the PDA NPs at two different wavelengths, which showed the strong synergistic effect of combining PTT and PDT within this nanoplatform.