Aggregation-Induced Emission Luminogen with Deep-Red Emission for Through-Skull Three-Photon Fluorescence Imaging of Mouse

Wang, Yalun; Chen, Ming; Alifu, Nuernisha; Li, Shiwu; Qin, Wei; Qin, Anjun; Tang, Ben Zhong; Qian, Jun

doi:10.1021/acsnano.7b05645

Cited by 157 publications

(105 citation statements)

References 45 publications

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“…At the imaging depth of 656 µm, a line intensity profile across a small capillary was plotted and its full width at half maximum (FWHM) is around 1.05 µm (calculated by Gaussian fitting). This FWHM value demonstrates high‐resolution imaging capability for two‐photon imaging, which is one of the highest values in in vivo deep tissue two‐photon brain imaging reported so far 3b,24b,25. These results prove that TPEPy‐FBS nanocomposites with high far‐red/NIR brightness, good photostability and biocompatibility are very promising for deep tissue and high‐resolution in vivo two‐photon imaging.…”

Section: Resultssupporting

confidence: 57%

Bright AIEgen–Protein Hybrid Nanocomposite for Deep and High‐Resolution In Vivo Two‐Photon Brain Imaging

Wang

Pan

et al. 2019

Adv Funct Materials

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Two-photon fluorescence imaging allows in vivo study of biological structures and activities in deep tissues, in which bright fluorophores with high photostability and good biocompatibility are highly desirable. Herein, a small-molecule fluorogen with aggregation-induced emission (AIEgen) is complexed with fetal bovine serum (FBS) proteins to develop a protein-sized AIEgen-protein hybrid nanocomposite (TPEPy-FBS) with bright far-red/ near-infrared (NIR) emission, excellent photostability, and low phototoxicity for deep and high-resolution in vivo two-photon brain vasculature imaging. Upon complexation with FBS, the fluorescence of TPEPy is greatly intensified and a sixfold enhancement is observed with 10% FBS in aqueous media. The yielded TPEPy-FBS shows good physical stability in aqueous media and the phototoxicity of TPEPy is dramatically inhibited after complexation with FBS. Moreover, TPEPy-FBS exhibits bright two-photon fluorescence in far-red/ NIR region and good photostability upon femtosecond laser excitation, which facilitates high performance in vivo imaging. A large imaging depth of 656 µm is obtained in brain vasculature network imaging with a high signalto-background ratio of 234, where a small blood capillary of 1.05 µm can be resolved at an imaging depth of 656 µm. Highlighted is a simple and versatile strategy to develop efficient two-photon probes for in vivo biological imaging.

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Section: Resultssupporting

confidence: 57%

Bright AIEgen–Protein Hybrid Nanocomposite for Deep and High‐Resolution In Vivo Two‐Photon Brain Imaging

Wang

Pan

et al. 2019

Adv Funct Materials

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“…Next, we examined the D-A odd effect on the photosensitization efficiency.A ss hown in Figure 3G,A IE-active TPT with aD -A-D structure has been successfully used for through-skull three-photon fluorescence imaging of mice. [20] According to our strategy, PTP with an A-D-A structure was designed. As expected, PTP exhibits ahigh F o of 45 %, being 2.7-fold higher than that of TPT (12 %) ( Figure 3H).…”

mentioning

confidence: 99%

Strategies to Enhance the Photosensitization: Polymerization and the Donor–Acceptor Even–Odd Effect

et al. 2018

Self Cite

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Ap articular challenge in the design of organic photosensitizers (PSs) with donor-acceptor (D-A) structures is that it is based on trial and error rather than specific rules.Now these challenges are addressed by proposing two efficient strategies to enhance the photosensitization efficiency:p olymerization-facilitated photosensitization and the D-A evenodd effect. Conjugated polymers have been found to exhibit ah igher 1 O 2 generation efficiency than their small molecular counterparts.F urthermore,P Ss with A-D-A structures show enhanced photosensitization efficiency over those with D-A-D structures.T heoretical calculations suggest an enhanced intersystem crossing (ISC) efficiency by these strategies.B oth in vitro and in vivo experiments demonstrate that the resulting materials can be used as photosensitizers in image-guided photodynamic anticancer therapy. These guidelines are applicable to other polymers and small molecules to lead to the development of new PSs.

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“…The AIEgen in solid state can also simultaneously generate four‐photon excited luminescence and third harmonic generation under 1950, 2010, and 2070 nm femtosecond laser excitation. In 2017, the authors further applied A26 for through‐skull three‐photon fluorescence imaging (3PFI) of brain–blood vessels . Measured via the nonlinear transmissivity method, the A26 molecules in chloroform solution had a large three‐photon absorbing cross section (σ 3 ) of 2.95 × 10 −79 cm 6 s −2 at 1550 nm.…”

Section: Live Body Imaging and Theranosticsmentioning

confidence: 99%

Section: Live Body Imaging and Theranosticsmentioning

confidence: 99%

Unity Makes Strength: How Aggregation‐Induced Emission Luminogens Advance the Biomedical Field

et al. 2018

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research fields to provide new opportunities for precise and personalized medical treatment of patients. [16][17][18][19][20][21][22][23][24][25][26][27] An ideal fluorescent agent should have low toxicity, high brightness, excellent stability, good selectivity, and versatile functionality. To date, a vast variety of synthetic fluorescent materials, including organic dyes, [28][29][30] fluorescent proteins, [31,32] inorganic quantum dots (QDs), [33,34] conjugated polymer nanoparticles (NPs), [35][36][37][38][39][40] metallic nanoclusters, [41] as well as upconversion NPs, [42][43][44] have been explored and demonstrated for biological applications.Among the above-mentioned fluorescent materials, synthetic organic dyes and dye-loaded fluorescent NPs have attracted special attention due to the good biocompatibility and easy availability. However, a considerable number of organic dyes are hydrophobic, which often form aggregation through π-π stacking in aqueous solutions and buffers even though different strategies have been applied to improve their water solubility. The serious π-π stacking interactions among dye molecules facilitate nonradiative pathways to relax the exciton energy, leading to partially or completely quenched fluorescence. This phenomenon is well known as aggregation-caused quenching (ACQ) effect, [45] which is the main obstacle of construction of highly emissive fluorescence bioprobes in complicated biological microenvironments. Although great efforts have been made from various aspects to overcome the notorious undesired ACQ effect, [46] it remains a major challenge for the significant improvement of traditional fluorescent bioprobes in biomedicine and life sciences.In 2001, Tang and co-workers discovered a novel fluorescent phenomenon that is opposite to the ACQ effect: the organic Figure 4. Confocal images of Hela cancer cells after incubation with A-D) A6-A9 (5 × 10 −6 m) for 15 min, respectively. Adapted with permission. [104]

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Aggregation-Induced Emission Luminogen with Deep-Red Emission for Through-Skull Three-Photon Fluorescence Imaging of Mouse

Cited by 157 publications

References 45 publications

Bright AIEgen–Protein Hybrid Nanocomposite for Deep and High‐Resolution In Vivo Two‐Photon Brain Imaging

Bright AIEgen–Protein Hybrid Nanocomposite for Deep and High‐Resolution In Vivo Two‐Photon Brain Imaging

Strategies to Enhance the Photosensitization: Polymerization and the Donor–Acceptor Even–Odd Effect

Unity Makes Strength: How Aggregation‐Induced Emission Luminogens Advance the Biomedical Field

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