Abstract
In this work, we exploit the versatile function of cationic phosphonium-conjugated polythiophenes to develop multifunctional platforms for imaging and combined therapy (siRNA delivery and photodynamic therapy). The photophysical properties (absorption, emission and light-induced generation of singlet oxygen) of these cationic polythiophenes were found to be sensitive to molecular weight. Upon light irradiation, low molecular weight cationic polythiophenes were able to light-sensitize surrounding oxygen into reactive oxygen species (ROS) while the highest were not due to its aggregation in aqueous media. These polymers are also fluorescent, allowing one to visualize their intracellular location through confocal microscopy. The most promising polymers were then used as vectors for siRNA delivery. Due to their cationic and amphipathic features, these polymers were found to effectively self-assemble with siRNA targeting the luciferase gene and deliver it in MDA-MB-231 cancer cells expressing luciferase, leading to 30–50% of the gene-silencing effect. In parallel, the photodynamic therapy (PDT) activity of these cationic polymers was restored after siRNA delivery, demonstrating their potential for combined PDT and gene therapy.
Highlights
Cancer is a multifaceted and complex disease, which remains one of the main causes of death, forcing researchers to continuously develop new anticancer treatments with high efficiency and specificity [1,2]
photodynamic therapy (PDT) uses photosensitizers (PSs), which generate reactive oxygen species (ROS) from molecular oxygen under light illumination and can directly lead to the cancer cell death mainly through apoptosis or necrosis, and indirectly by inducing tumor vasculature shutdown and recruitment of immune mediators [6]. This operational dependence in oxygen in a tumor microenvironment can lead to tumor hypoxia, trigger the signaling cascade mediated by hypoxia inducible factor (HIF) and release pro-angiogenic growth factors, which are responsible for cancer cell survival or tumor regrowth [7]
Poly(3-(6’-bromohexyl)thiophene) precursors (P3HT-Br) were first synthesized by Kumada Catalyst-Transfer Condensative Polymerization (KCTCP) (Scheme 1), which enables the preparation of Nanomaterials 2020, 10, x FOR PEER REVIEW
Summary
Cancer is a multifaceted and complex disease, which remains one of the main causes of death, forcing researchers to continuously develop new anticancer treatments with high efficiency and specificity [1,2]. Their conjugated backbone determines their intrinsic optical properties, such as absorption, fluorescence, and light-harvesting ability, enabling their use in the development of chemo- and biosensors, as well as in bioimaging applications [34,35,36,37] Exploiting all these versatile features, CPEs were exploited as imaging systems and gene delivery vehicles exhibiting low toxicity and good photostability, together with high delivery and transfection efficiencies [38,39,40,41,42]. Their potential to deliver genetic material and act as a PS in a cooperative manner was examined
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