Aggregation Regulation And Phototheranostics Applications Of A-D-A Type π-conjugated Molecules

With the development of π-conjugated materials,optics,and nanotechnology,phototheranostics based on π-conjugated materials gradually show great potential in cancer diagnosis and treatment.In order to achieve good phototheranostics performance,conventional strategies usually require multifunctional components,which usually require complex fabrication and bring obstacles to industrial production and clinical translation.It is essential to explore simple phototheranostics nanoplatforms with highperformance therapeutic efficacy and imaging capabilities to overcome these challenges.A-D-A type π-conjugated molecules have gradually emerged in the field of phototheranostics due to their strong visible light and near-infrared(NIR)absorption,easy-to-modify modular structure and optical bandgap,and abundant excited states.However,its large π-conjugated structure leads to high hydrophobicity,which usually requires dispersion into an aqueous phase by the nanoprecipitation method.Hydrophobic forces drive molecular aggregation in this process,resulting in π-π interactions.The electronic coupling induced by intermolecular π-π stacking will significantly alter the therapeutically relevant optoelectronic properties.Therefore,it is a critical issue in regulating the properties of π-conjugated molecules for studying and controlling the π-πelectron coupling effect in the aggregated state.Because of the above problems,this paper uses three strategies to control the aggregation state of A-D-A type π-conjugated molecules: side chain rigidity regulation,side chain positioning chlorine-mediated,and introduction of end group interactions.Regulated to achieve more efficient phototheranostics performance.The main research content and results are summarized as follows:In the study of the effect of the side chain rigidity of A-D-A type π-conjugated molecule on the aggregation and phototherapy properties,BDTR9-OC6,BDTR9-OC8,BDTR9-C8,and BDTR9-EH with the same π-conjugated main chain and different stiffness side chain was successfully constructed by replacing the side chain with different steric hindrance and rigidity on the central nucleus.BDTR9-OC6,BDTR9-OC8,BDTR9-C8,and BDTR9-EH showed similar photophysical properties in a monodisperse state.As the molecular side chains become more rigid,the H-aggregation in the aggregated state is gradually suppressed,and a tendency to form J-aggregation appears.During this change,it can be observed that the rigid side chains of BDTR9-C8 inhibit the formation of H-aggregates and lead to a relatively amorphous condensed state,which will facilitate the efficient transport of photogenerated excitons and phonons,thus exhibiting simultaneous enhanced NIR-II fluorescence and photoacoustic imaging signals.Photothermal therapy guided by dual-modalities of BDTR9-C8 nanoparticles NIR-II fluorescence and photoacoustic imaging achieved effective inhibition or elimination of tumors.This study realizes the adequate adjustment of side chain rigidity to aggregated molecular packing.It provides more ideas for exploring high-performance NIR-II fluorescence and photoacoustic imaging-guided photothermal therapy materials.Besides the optical and photothermal properties,the π-π stacking also determines the energy and electron transfer in the aggregated state,which plays a crucial role in the photodynamic reaction.Three kinds of phototheranostics molecules,BTIC-4Cl-TCl-β,BTIC-4Cl-TCl-γ,and BTIC-4Cl-T,were synthesized by substituted chlorine at the central side chain of the A-D-A π-conjugated molecule in different positions.Spectral and singlecrystal X-ray diffraction analysis revealed that BTIC-4Cl-TCl-β has Cl···H interactions and multiple S···S The tight molecular packing obtained by the non-covalent interaction and the final quasi-three-dimensional network structure helps to improve the photodynamic efficiency.At the same time,the less H-aggregation mode contributes to the fluorescence performance.As a result,the fluorescence imaging-guided photodynamic therapy system based on BTIC-4Cl-TCl-β nanoparticles shows excellent performance in vitro and in vivo.In this study,two-dimensional side chains and positioning chlorine-mediated strategies can effectively regulate the accumulation of aggregated molecules,which boosts the exploration of high-performance fluorescence imaging-guided photodynamic therapy materials.In addition to side chain regulation,the introduction of end-group interactions is also an effective means to regulate the aggregation state of π-conjugated molecules.Three kinds of Phototheranostics molecules BTIC-4Cl with halogen bonds,BTIC-2OH with hydrogen bonds,and BTIC-OH-2Cl with two forces simultaneously were successfully constructed by substituting chlorine and hydroxyl on the end groups of A-D-A type π-conjugated molecules.Chlorine-substituted end groups can significantly reduce the band aggregation mode in aggregation to obtain strong fluorescence emission.In contrast,the hydrogen-bonding interactions of the hydroxyl end groups can induce stronger π-πelectronic coupling.BTIC-2OH exhibits more than 4 times faster electron transport in aggregates than BTIC-4Cl.Stronger π-π electron coupling and faster energy/electron transport contribute to enhanced PDT efficiency.Owing to the effects of π-π electron coupling on the fluorescence and PDT efficiency,an asymmetrically substituted derivative,BTIC-OH-2Cl,was prepared,exhibiting balanced phototheranostics properties.Cell and in vivo experiments prove that BTIC-OH-2Cl nanoparticles are safe and reliable NIR-II fluorescence-guided efficient PDT materials.This study shows that the introduction of terminal group interaction strategy can effectively adjust the characteristics of highly hydrophobic A-D-A π conjugated molecules to improve the phototheranostics performance.