Tailoring the properties of a hypoxia-responsive 1,8-naphthalimide for imaging applications

Yang, Kylie; Leslie, Kathryn G.; Kim, Sally Yunsun; Kalionis, Bill; Chrzanowski, Wojciech; Jolliffe, Katrina A.; New, Elizabeth J.

doi:10.1039/c7ob03164e

Cited by 27 publications

(23 citation statements)

References 23 publications

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“…As is the case with DMSC primary cells, DMSC23 cells are resistant to oxidative stress due to the preconditioning of the placenta‐derived tissue where the cells are isolated from . We previously showed that DMSC23 are more resistant to hypoxic stress compared to CMSC29 . Since EVs convey similar properties to the cells which they are secreted from, DMSC23 EVs were expected to reduce oxidative stress in an established in vitro model of lung injury; LPS‐injured BEAS‐2B lung epithelial cells.…”

Section: Resultsmentioning

confidence: 99%

Placenta Stem/Stromal Cell–Derived Extracellular Vesicles for Potential Use in Lung Repair

et al. 2019

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Many acute and chronic lung injuries are incurable and rank as the fourth leading cause of death globally. While stem cell treatment for lung injuries is a promising approach, there is growing evidence that the therapeutic efficacy of stem cells originates from secreted extracellular vesicles (EVs). Consequently, EVs are emerging as next‐generation therapeutics. While EVs are extensively researched for diagnostic applications, their therapeutic potential to promote tissue repair is not fully elucidated. By housing and delivering tissue‐repairing cargo, EVs refine the cellular microenvironment, modulate inflammation, and ultimately repair injury. Here, the potential use of EVs derived from two placental mesenchymal stem/stromal cell (MSC) lines is presented; a chorionic MSC line (CMSC29) and a decidual MSC cell line (DMSC23) for applications in lung diseases. Functional analyses using in vitro models of injury demonstrate that these EVs have a role in ameliorating injuries caused to lung cells. It is also shown that EVs promote repair of lung epithelial cells. This study is fundamental to advancing the field of EVs and to unlock the full potential of EVs in regenerative medicine.

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Section: Resultsmentioning

confidence: 99%

Placenta Stem/Stromal Cell–Derived Extracellular Vesicles for Potential Use in Lung Repair

et al. 2019

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“…Many of the naphthalimides with substituents at the C3 and C5 position have either been previously reported, or were readily accessible by adaptation of previous methods (Scheme S1). Substitution at the C6 position, however, is rarely reported in the literature and was less straightforward for many of the substituents.…”

Section: Resultsmentioning

confidence: 99%

Expanding the Breadth of 4‐Amino‐1,8‐naphthalimide Photophysical Properties through Substitution of the Naphthalimide Core

Leslie

Jacquemin

New

et al. 2018

Chemistry A European J

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Fluorescent sensors that illuminate specific molecules and chemical events allow the selectivea nd sensitive study of the cellular environment. At the centre of this technology lies the fluorescent reporter molecule, and it is therefore crucial to provide ab readth of fluorophores with varying photophysical and biological behaviour.4 -Amino-1,8naphthalimides are commonly employed in fluorescent sensors, but the narrow range of structurald erivativesl imits versatility of application.H ere we report the synthesis and investigation of as et of twelve 4-amino-1,8-naphthalimides bearinga na dditional substituent on the aromatic core. Pho-tophysical characterisation and time-dependent density functional theory studies provided insights into the structure-photophysical property relationships of these derivatives, which show an expanded range of emissionw avelengths and other photophysical properties. These compounds coulda ll be visualised within cells by confocal microscopy,s howingc ytoplasmic or lipid droplet localisation. Our studies have demonstratedt hat simple structural modification of 4-amino-1,8-naphthalimides provides derivatives with considerable breadtho fb ehaviour that lend valuable versatility to the design of fluorescents ensors.

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“…We envisaged that the incorporation of nitro‐aryl substituents onto the 4‐amino‐1,8‐naphthalimide scaffold would provide a suitable model system in which to examine the above properties, anticipating that the resulting molecules would be useful probes for sensing hypoxic environments, since aromatic nitro compounds are known to be reduced to the corresponding aniline in hypoxic conditions . Nitro groups generally quench fluorescence, whereas in amine‐containing fluorophores, strong fluorescence is common.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Nitro‐Aryl Functionalised 4‐Amino‐1,8‐Naphthalimides and Their Evaluation as Fluorescent Hypoxia Sensors

Adair

Trinh

Vérité

et al. 2020

Chemistry A European J

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Fluorescent sensors are av ital research tool, enabling the study of intricate cellular processes in as ensitive manner.T he design and synthesis of responsive and targeted probes is necessary to allow such processes to be interrogated in the cellular environment. This remains ac hallenge, and requires methods for functionalisationo ff luorophores with multiple appendages for sensing and targeting groups. Methods to synthesise more structurally complex derivatives of fluorophores will expand their potential scope. Most known 4-amino-1,8-naphthalimides are only functionalised at imide and 4-positions, ands tructuralm odifications at additional positions will increase the breadth of their utility as responsive sensors.I nt his work, methodsf or the incorporation of ah ypoxias ensing group to 4-amino-1,8-naphthali-mide were evaluated. An intermediate was developed that allowedu st oi ncorporateasensing group, targeting group, and ICT donor to the naphthalimide core in am odularf ashion. Synthetic strategies for attaching the hypoxias ensing group and how they affected the fluorescenceo ft he naphthalimide were evaluated by photophysical characterisation and time-dependent density functional theory.A ne xtracellular hypoxia probe was then rationally designed that could selectively image the hypoxic and necrotic region of tumour spheroids. Our results demonstrate the versatility of the naphthalimide scaffold and expand its utility.T his approach to probe design will enable the flexible, efficient generation of selective, targeted fluorescents ensors for variousb iological purposes.

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Tailoring the properties of a hypoxia-responsive 1,8-naphthalimide for imaging applications

Cited by 27 publications

References 23 publications

Placenta Stem/Stromal Cell–Derived Extracellular Vesicles for Potential Use in Lung Repair

Placenta Stem/Stromal Cell–Derived Extracellular Vesicles for Potential Use in Lung Repair

Expanding the Breadth of 4‐Amino‐1,8‐naphthalimide Photophysical Properties through Substitution of the Naphthalimide Core

Synthesis of Nitro‐Aryl Functionalised 4‐Amino‐1,8‐Naphthalimides and Their Evaluation as Fluorescent Hypoxia Sensors

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