Esterase-Activated Theranostic Prodrug for Dual Organelles-Targeted Imaging and Synergetic Chemo-Photodynamic Cancer Therapy

Zhuang, Jiabao; Li, Nan; Zhang, Yaling; Li, Baolin; Wen, Hanqi; Zhang, Xinchan; Zhang, Tianyu; Zhao, Na; Tang, Ben Zhong

doi:10.31635/ccschem.021.202100985

Cited by 45 publications

(35 citation statements)

References 29 publications

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“…In a recent study, we further extended the application scope of PDT and achieved the customizable photodynamic patterning of living organisms with AIE polyelectrolytes (Figure 7F−G), indicating its potential in tissue engineering and biochips. 4 In addition to single-mode PDT, we also developed a series of charged AIEgen-based multimode theranostic materials that integrated PDT with photothermal therapy, 53,60 chemotherapy, 61 and/or phagotherapy, 42 which can be used for the establishment of synergistic therapeutic systems.…”

Section: Photodynamic Therapymentioning

confidence: 99%

Bringing Inherent Charges into Aggregation-Induced Emission Research

2022

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Metrics & MoreArticle Recommendations CONSPECTUS: Charged organic molecules, such as DNA, RNA, proteins, and polysaccharides, are ubiquitous and indispensable in natural living systems, which possess specific biological functions to interact with oppositely charged species via electrostatic attraction.The molecules with inherent charges typically differentiate themselves from the neutral ones with unique attributes (e.g., ionic interactions and high polarity), thereby playing a pivotal role in a broad spectrum of areas, including supramolecular chemistry, structural biology, and materials science. It is thus of great importance to explore and develop various charged organic systems for biomimicry and the creation of functional materials. In 2001, our group reported a peculiar luminogen that exhibited weak emission in solution but had significantly enhanced emission in aggregates, and we, for the first time, coined this phenomenon as aggregation-induced emission (AIE). The AIE concept significantly changes the cognition of the scientific community toward classic photophysical phenomena. Since the discovery of this unusual luminescence phenomenon, AIE luminogens (AIEgens) have attracted extensive attention from researchers in a plethora of disciplines because of their high brightness in aggregates, large Stokes shift, excellent photostability, and good biocompatibility. In the past 10 years, our laboratory has expended a great amount of effort to bring inherent charges into AIE research and acquired fruitful achievements.In this Account, we summarize the progress of charged AIE systems primarily made by our laboratory. We start with a brief introduction to charged AIEgens and then discuss their design strategies from molecular and topological perspectives, respectively. Next, we review the unique properties of charged AIEgens, including D−A interactions, anion−π + interactions, and intermolecular electrostatic interactions, with an emphasis on how they differentiate themselves from the neutral analogs. On the one hand, positively charged AIEgens exhibit unique photophysical properties by forming typical donor−acceptor structures to manipulate the emission wavelength or initiate ultralong persistent luminescence. On the other hand, positively charged AIEgens exhibit unique physiochemical properties, such as an adjustable targeting capability toward biological targets and a strong capability for the generation of reactive oxygen species. Furthermore, we showcase the applications of charged AIEgens in imaging and diagnosis, photodynamic therapy, gas separation, and solar desalination. Finally, we conclude this Account with a summary and some perspectives regarding the existing challenges and future directions. We hope that this Account can spark new ideas and inspire scientists from different disciplines to explore this nascent yet promising research area.

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Section: Photodynamic Therapymentioning

confidence: 99%

Bringing Inherent Charges into Aggregation-Induced Emission Research

2022

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“…Cell Colocalization of TPE-N(Ph)-DBT-PH Nanosensor. 24 The above adherent RAW 264.7 cells were washed with 1× PBS buffer initially. Then 1 mmol L −1 Lyso-Tracker Green and 1 mmol L −1 Mito-Tracker Green were placed in the cell plates in DMEM to give a final concentration of 100 nM Lyso-Tracker Green and 100 nM Mito-Tracker Green, respectively.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Such results suggest that the TPE-N(Ph)-DBT-PH nanosensor is able to simultaneously target mitochondria and lysosomes in RAW 264.7 cells. 24,36 With the TPE-N(Ph)-DBT-PH nanosensor in hand, the real-time intracellular 1 O 2 , a possible effector of eukaryotic gene expression during biological regulation, was detected for the first time. The endotoxin LPS and protein kinase C activator PMA are known to stimulate the respiratory burst of phagocytes.…”

Section: ■ Introductionmentioning

confidence: 99%

An Aggregation-Induced Emission Nanosensor for Real-Time Chemiluminescent Sensing of Light-Independent Intracellular Singlet Oxygen

Lyu

Cheng

Liu³

et al. 2022

ACS Appl. Mater. Interfaces

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Characterizing the transient ultratrace light-independent intracellular singlet oxygen (1O2), which plays a vital role in multiple biological processes in living organisms, brings about tremendous help for understanding the nature of 1O2-mediated or related bioevents. Nevertheless, an approach to detect the light-independent intracellular 1O2 is hard to find. Herein, we developed a chemiluminescent nanosensor by compacting a great number of TPE-N(Ph)-DBT-PH molecules in one nanostructure via autoaggregation. Taking advantage of the aggregation-induced emission property, this TPE-N(Ph)-DBT-PH nanosensor is highly fluorescent and promises a bright red-light CL and the convenience of mapping in vivo sensor distribution. Experiments demonstrate the nanosensor’s unprecedented selectivity toward 1O2 against other reactive oxygen species. The 3.7 nmol L–1 limit of detection renders this nanosensor with the best-known sensitivity of 1O2 chemical sensors. Meanwhile, fluorescence confocal microscope imaging results suggest that our nanosensor simultaneously targets mitochondria and lysosomes in RAW 264.7 cells via the energy-dependent endocytosis pathway, thereby implying an attractive potential for the detection of intracellular 1O2. Such a potential is demonstrated by detecting 1O2 in RAW 264.7 cells during a lipopolysaccharide and phorbol myristate acetate stimulated respiration burst. This study represents the first approach to detect light-independent intracellular 1O2 during cell bioregulation. Thus, our nanosensor provides an effective tool for investigating the 1O2-related bioprocesses and pathological processes.

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“…We clarified the mechanism of the esterase-catalyzed hydrolysis of ER-CE by the molecular docking method, and the cholesterol esterase from Bos taurus was used as the template enzyme. 22,23 As shown in Fig. 2, the interaction between ER-CE and cholesterol esterase was mainly through the formation of hydrogen bonds with Ser26 (A) and Arg133 (A).…”

mentioning

confidence: 98%