期刊
MOLECULAR PHARMACEUTICS
卷 18, 期 9, 页码 3623-3637出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.1c00597
关键词
polydopamine; photodynamic therapy; photothermal therapy; thioketal; ROS-responsive release
资金
- French Ministry of Research
- PTT research from the ANR JCJC [Project-ANR-19-CE09-0015]
- MITI Auto-organisation [2021]
- ANR [ANR-10-LABX-33]
Polydopamine nanoparticles have been considered for their multifunctional properties including photothermal and photodynamic activities. In this study, PDA NPs were modified with SH-PEG polymers bearing a reactive oxygen species-cleavable linker coupled to trisulfonatedtetraphenylporphyrin for PDT applications. The efficient grafting of PS-conjugated PEG on PDA was demonstrated in situ and the photoinduced release of PS was confirmed by H-1 NMR. In vitro experiments on human esophageal cells showed the strong synergistic effect of combining PTT and PDT within this nanoplatform.
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 autooxidative 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 trisulfonatedtetraphenylporphyrin (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 H-1 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.
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