Visualizing Photodynamic Therapy in Transgenic Zebrafish Using Organic Nanoparticles with Aggregation-Induced Emission

Photodynamic therapy(PDT) employs accumulation of photosensitizers(PSs) in malignant tumor tissue followed by the light-induced generation of cytotoxic reactive oxygen species to kill the tumor cells. The success of PDT depends on optimal PS dosage that is matched with the ideal power of light. This in turn depends on PS accumulation in target tissue and light administration time and period.As theranostic nanomedicine is driven by multifunctional therapeutics that aim to achieve targeted tissue delivery and image-guided therapy, fluorescent PS nanoparticle(NP)accumulation in target tissues can be ascertained through fluorescence imaging to optimize the light dose and administration parameters. In this regard, zebrafish larvae provide a unique transparent in vivo platform to monitor fluorescent PS bio-distribution and their therapeutic efficiency. Using fluorescent PS NPs with unique aggregation-induced emission characteristics, we demonstrate for the first time the real-time visualization of polymeric NP accumulation in tumor tissue and, more importantly, the best time to conduct PDT using transgenic zebrafish larvae with inducible liver hyperplasia as an example.

Binary organic nanoparticles with enhanced reactive oxygen species generation capability for photodynamic therapy

Photodynamic therapy(PDT)takes advantage of photosensitizers(PSs)to generate reactive oxygen species(ROS)for cell killing when excited by light.It has been widely used in clinic for therapy of multiple cancers.Currently,all the FDA-approved PSs,including porphyrin,are all small organic molecules,suffering from aggregation-caused quenching(ACQ)issues in biological environment and lacking tumor targeting capability.Nanoparticles(NPs)with size between 20 nm and 200 nm possess tumor targeting capability due to the enhanced permeability and retention(EPR)effect.It is urgent to develop a new strategy to form clinical-approved-PSs-based NPs with improved ROS generation capability.In this study,we report a strategy to overwhelm the ACQ of porphyrin by doping it with a type of aggregation-induced emission(AIE)luminogen to produce a binary NPs with high biocompatibility,and enhanced fluorescence and ROS generation capability.Such NPs can be readily synthesized by mixing a porphyrin derivative,Ce6 with a typical AIE luminogen,TPE-Br.Here,our experimental results have demonstrated the feasibility and effectiveness of this strategy,endowing it a great potential in clinical applications.

Uptake and Intracellular Fate of Fluorophore Labeled Metal−Organic-Framework(MOF)Nanoparticles

The uptake and the fate of Zr-based metal−organic-framework nanoparticles labeled with organic fluorophores in HeLa cells has been monitored with fluorescence detection and elemental analysis.The nanoparticles have been selected as a model system of carrier nanoparticles(here Zr-based metal−organic-framework nanoparticles)with integrated cargo molecules(here organic fluorophores),with aze that does not allow for efficient exocytosis,a material which only partly degrades under acidic conditions as present in endosomes/lysosomes,and with limited colloidal stability.Data show that,for Zr-based metal−organic-framework nanoparticles of 40 nm size as investigated here,the number of nanoparticles per cells decreases faster due to particle redistribution upon proliferation than due to nanoparticle exocytosis and that,thus,also for this system,exocytosis is not an efficient pathway for clearance of the nanoparticles from the cells.

Achieving purely organic room temperature phosphorescence in aqueous solution

Purely organic room temperature phosphorescence(RTP)materials have aroused increasing interests in recent years and have been widely applied in anticounterfeiting,biological imaging,sensing,etc.Currently,these materials can be efficiently developed in crystalline states and amorphous polymer-doped systems.However,achieving organic RTP in solution,especially in water solution,is still a formidable challenge.Recently,reports on aqueous phase RTP have been increasing and some feasible design strategies have been proposed;however,related investigations are still limited and there is a lack of systematic reviews.Therefore,we summarized the recent cases of aqueous phase organic RTP emission with primarily focusing on the RTP properties and efficient design strategies(e.g.,forming nanoparticles from phosphorescent molecules and macrocyclic supramolecular assembly).Moreover,promising applications of the aqueous phase organic RTP emission in bio-imaging and sensing were discussed.Some detailed perspectives concerning materials design and application were provided with the hope to provide inspiration for the future development of aqueous phase organic RTP.

Elucidating the excited-state dynamics behavior in near-infrared Bodipy dye and aggregates toward biophotonics

Photo-induced excited-state dynamics within organic materials fundamentally determine their photophysical properties for various applications,and thus understanding the primary excited-state dynamics behavior is of fundamental and practical significance.Until recently,the excited-state dynamics of organic materials towards biophotonics have been rarely studied,although numerous endeavors have been devoted to the design of organic materials for biophotonics.Herein,various spectroscopy technologies including femtosecond transient absorption(fs-TA)spectroscopy clearly reveal a totally different excited state dynamics behavior within Bodipy monomer(2B-BDP dye)and aggregates(2B-BDP NPs),indicating strongly morphology dependent character.2B-BDP dye undergoes an ultrafast conversion from S1 to intramolecular charge transfer(ICT)state for subsequent photoluminescence(PL)and nonradiative(NR)decay,while 2B-BDP NPs show an accelerated excited-state deactivation mainly through S1→S0 NR decay.The potential bioapplications based on the corresponding excited state dynamics behavior are discussed together with experimental results.Interestingly,the accelerated NR decay in 2B-BDP NPs does not yield a stronger photoacoustic(PA)signal than that in 2B-BDP dye,which violates the conventional wisdom that faster NR decay would benefit the photothermal effects for better photoacoustic imaging(PAI).These insightful and fundamental observations of the excited-state dynamics may contribute an alternative approach at the molecular level towards the future design of functional Bodipy-based organic molecules with desirable performances.