Design,Fabrication And Application Of Two-Photon Near-Infrared Fluorescent Nanoprobes For Photodynamic Therapy

Photodynamic therapy(PDT)has garnered much attention owing to its non-invasiveness,negligible side effects,few drug resistance,low toxicity,and high spatiotemporal selectivity.PDT uses photosensitizers and light to produce ROS that induce cells apoptosis and tissues destruction.In this contribution,D-π-A structured photosensitizers are prepared and the optical property,cell cytoxicity,biocompatibility and ROS generation capacity of photosensitizers are investigated.We also evaluate the near-infrared fluorescence and two-photon imaging property,explore the organelle targeted ability,and investigate the photodynamic therapy anti-tumor property.Our work can be divided into two parts.Part One:In this dissertation,by using triphenylamine as electron-donating group,rhodanic as electron-withdrawing units,and thiophene as π bridge,near-infrared fluorescent photosensitizer with D-π-A structure was constructed.And it was precipitate from DMSO to water to prepare nanoparticles TTR-CN NPs.TTR-CN NPs demonstrates near-infrared(NIR)emission(centred around 740 nm),good biocompatibility and superior photostability,which can act as two-photon fluorescent agent for clear visualization of living cells and vascular in tissues with deep-tissue penetration.Furthermore,TTR-CN NPs can efficiently produce ROS lysosome in situ upon light irradiation to damage lysosome,up-regulate LC3 and Beclinl,increase BAX release,and induce cell apoptosis.Both in vitro and in vivo studies revealed that TTR-CN NPs has effective anti-cancer potential.All these results confirm that TTR-CN NPs can serve as potential platform for two-photon fluorescent imaging of cells/tissues and photodynamic therapy.Part Two:we prepare a new mitochondrial targeting two-photon photosensitizer.The two-photon photosensitizer is A-π-D-π-A structured organic small molecule fluorophore(TTP-2PI),which is designed via triphenylamine as donor,pyridinium ion as acceptor,and thiophene as π bridge.TTP-2PI serves as efficient ROS generator with red emission(λem=629 nm),low cytotoxicity,favorable biocompatibility,excellent photostability,mitochondria-targeted properties,and two photon imaging capacity,which can act as two-photon fluorescent agent for clear visualization of cells and vascular in tissues with deep-tissue penetration.9,10-Anthracenediyl-bis(methylene)-dimalonic acid(ABDA)was utilized as ROS indicator to investigate the ROS production ability.Consumption rate of ABDA upon the TTP-2PI under irradiation is calculated to be 194.84 nmol/min,confirming the excellent ROS generation ability of TTP-2PI.Both in vitro and in vivo studies revealed that TTP-2PI exhibited has effective anticancer potential and is amenable to two-photon stimulated photodynamic therapy of tumor.Our work provides the guide for design of new two-photon photosensitizer.