Polythiophenes with Cationic Phosphonium Groups as Vectors for Imaging, siRNA Delivery, and Photodynamic Therapy

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.

Progress of Photodynamic and RNAi Combination Therapy in Cancer Treatment

“…Under laser irradiation, the low molecular weight cationic polythiophene photosensitized the surrounding oxygen into ROS. Due to their cationic and amphiphilic properties, these polymers were found to effectively assemble with siRNA targeting luciferase genes to achieve gene inhibition, while PDT activity of these cationic polymers was recovered after siRNA delivery, demonstrating their potential to combine PDT with RNAi therapy …”

Strategies to Improve Photodynamic Therapy Efficacy of Metal-Free Semiconducting Conjugated Polymers

“… 48 Gary Bobo prepared amphiphilic cationic phosphine-based polythiophene P3. 49 Moreover, Zhang prepared water-soluble P4 with high 1 O 2 quantum yield (42%), photostability and pH stability. 50 Based on P4, Zhang shortened the hydrophobic carbon chain and prepared pure water-soluble P5 for enhanced PDT.…”

“…Meanwhile, the photodynamic activity of P3 was restored after siRNA delivery, proving their potential in the combination of PDT and gene therapy. 49 …”

“…Meanwhile, the photodynamic activity of P3 was restored after siRNA delivery, proving their potential in the combination of PDT and gene therapy. 49 Thus, improving the solubility by side chain modification could prolong the duration of efficacy in vivo. Adjusting the molecular composition of polymer could improve the electron and energy transfer in PDT and promote ROS generation.…”

Fluorescent Polymers Conspectus

“…This is especially advantageous due to its superior visco-elastic and mechanical properties, which aid in the manufacturing of new devices [ 14 , 15 , 16 , 17 , 18 , 19 ]. FPs, similar to small fluorescent molecules, have a wide range of uses for sensing [ 20 , 21 ] and imaging [ 22 , 23 , 24 , 25 , 26 , 27 ], optoelectronics [ 28 ], fluorescent bioprobes [ 29 ], molecular imaging [ 30 ], photodynamic treatments [ 31 ], OLEDs [ 32 ], storage data security [ 33 ], encryption [ 34 ], anti-counterfeiting materials [ 35 ], and other fields [ 27 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ].…”