A fluorescence and photoactivity dual-activatable prodrug with self-synergistic magnification of the anticancer effect

Li, Jun; Ni, Xiang; Zhang, Jingtian; Zhang, Xiaoyan; Zheng, Donghui

doi:10.1039/c9qm00081j

Cited by 21 publications

(11 citation statements)

References 59 publications

(63 reference statements)

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“…Phototheranostics, as a powerful cancer treatment protocol with the integrated functionalities of light-driven diagnostic imaging In addition, recent advances have demonstrated that AIEgens can also serve as phototheranostic agents for multimodal imaging-guided synergistic therapy through rational molecular design, benefiting from the inherent capabilities of AIEgens as an extraordinary template for subtly regulating the balance between radiative and nonradiative decays. [24][25][26][27][28] It is known that the photophysical properties of AIEgens are vital for the phototheranostic applications according to the Jablonski diagram. [2] An AIEgen absorbs the photon energy along with the transition of its electrons from the ground state to higher energy states followed by the energy dissipation process which generally involves three pathways corresponding to different phototheranostic functions: (1) fluorescence imaging/diagnosis through radiative decay pathway; (2) photothermal therapy (PTT) and photoacoustic imaging via thermal deactivation process (nonradiative decay pathway); (3) through intersystem crossing (ISC) for phosphorescence afterglow imaging and/or generation of cytotoxic reactive oxygen species (ROS) for photodynamic therapy (PDT).…”

Section: Introductionmentioning

confidence: 99%

Add the Finishing Touch: Molecular Engineering of Conjugated Small Molecule for High‐Performance AIE Luminogen in Multimodal Phototheranostics

et al. 2021

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Among the multiple diagnostic imaging, fluorescence imaging (FLI) possesses several distinct advantages including minimal invasiveness, superb sensitivity, and high spatiotemporal resolution. [8][9][10] However, conventional organic fluorophores usually suffer from the aggregation-caused quenching (ACQ) effect due to intermolecular π-π stacking caused by the planar molecule conformation, thereby resulting in weakened or vanished fluorescence emission upon the formation of aggregates in the physiological environment, which seriously hampers their biological applications. [11,12] Given the circumstances, emerging research interest is the aggregation-induced emission (AIE), which refers to a photophysical phenomenon wherein a novel family of propeller-shaped luminogens with twisted structural conformation are weakly emissive or nonemissive in the single-molecule state, but are induced to emit intensely in the aggregates through a mechanism of the restriction of intramolecular motions (RIM). [13][14][15][16][17][18][19][20][21][22][23] AIE luminogens (AIEgens) have triggered state-ofthe-art developments in FLI, thanks to their intrinsic properties including high signal-to-noise ratio and high photostability. Phototheranostics based on luminogens with aggregation-induced emission (AIE) characteristics is captivating increasing research interest nowadays. However, AIE luminogens are inherently featured by inferior absorption coefficients (ε) resulting from the distorted molecular geometry. Besides, molecular innovation of long-wavelength light-excitable AIE luminogens with highly efficient phototheranostic outputs is an appealing yet significantly challenging task. Herein, on the basis of a fused-ring electron acceptor-donator-acceptor (A-D-A) type molecule (IDT) with aggregation-caused quenching (ACQ)properties, molecular engineering smoothly proceeds and successfully yields a novel AIE luminogen (IDT-TPE) via simply modifying tetraphenylethene (TPE) moieties on the sides of IDT backbone. The AIE tendency endows IDT-TPE nanoparticles with enhanced fluorescence brightness and far superior fluorescence imaging performance to IDT nanoparticles for mice tumors. Moreover, IDT-TPE nanoparticles exhibit near-infrared light-excitable features with a high ε of 8.9 × 10 4 m −1 cm −1 , which is roughly an order of magnitude higher than that of most previously reported AIE luminogens. Combining with their reactive oxygen species generation capability and extremely high photothermal conversion efficiency (59.7%), IDT-TPE nanoparticles actualize unprecedented performance in multimodal phototheranostics. This study thus brings useful insights into the development of versatile phototheranostic materials with great potential for practical cancer theranostics.

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Section: Introductionmentioning

confidence: 99%

Add the Finishing Touch: Molecular Engineering of Conjugated Small Molecule for High‐Performance AIE Luminogen in Multimodal Phototheranostics

et al. 2021

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“…In this case, regardless of the extent to which the ligand ratio is elevated on the NP surfaces, the cellular uptake will not be increased (Kibria et al, 2011;Takara et al, 2012;Mei et al, 2014). To overcome this barrier and promote the cellular uptake efficacy, a dual-ligand targeted drug delivery system with the aim of reinforcing the tumor-targeting specificity has arisen (Jang et al, 2015;Mezghrani et al, 2015;Yang et al, 2015;Li et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Dual-Targeting Nanoparticle-Mediated Gene Therapy Strategy for Hepatocellular Carcinoma by Delivering Small Interfering RNA

Zheng

Jiang

et al. 2020

Front. Bioeng. Biotechnol.

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As a gene therapy strategy, RNA interference (RNAi) offers tremendous tumor therapy potential. However, its therapeutic efficacy is restricted by its inferior ability for targeted delivery and cellular uptake of small interfering RNA (siRNA). This study sought to develop a dual-ligand nanoparticle (NP) system loaded with siRNA to promote targeted delivery and therapeutic efficacy. We synthesized a dual receptor-targeted chitosan nanosystem (GCGA), whose target function was controlled by the ligands of galactose of lactobionic acid (LA) and glycyrrhetinic acid (GA). By loading siPAK1, an siRNA targeting P21-activated kinase 1 (PAK1), a molecular-targeted therapeutic dual-ligand NP (GCGA–siPAK1) was established. We investigated the synergistic effect of these two targeting units in hepatocellular carcinoma (HCC). In particular, GCGA–siPAK1 enhanced the NP targeting ability and promoted siPAK1 cell uptake. Subsequently, dramatic decreases in cell proliferation, invasion, and migration, with an apparent increase in cell apoptosis, were observed in treated cells. Furthermore, this dual-ligand NP gene delivery system demonstrated significant anti-tumor effects in tumor-bearing mice. Finally, we illuminated the molecular mechanism, whereby GCGA–siPAK1 promotes endogenous cell apoptosis through the PAK1/MEK/ERK pathway. Thus, the dual-target property effectively promotes the HCC therapeutic effect and provides a promising gene therapy strategy for clinical applications.

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“…To improve the efficacy of cancer chemotherapeutics, in 2019, Ding and Zheng reported a fluorescence and photoactivity dual‐activatable prodrug 28a , which was composed of a 4‐dimethylamino‐2′‐hydroxychalcone fluorogen with AIE characteristics, a disulfide bond, and the anticancer drug hydroxycamptothecin. [ 95 ] Utilizing an amphiphilic copolymer as the encapsulation carrier, 28a nanoparticles (about 126 nm in size) in aqueous solution were obtained, and these were favorable for in vivo applications. Upon addition of GSH, the disulfide bonds were cleaved, followed by release of active anticancer drug 28d and compound 28e , which could emit brighter AIE fluorescence and generate ROS under light irradiation for synergistic treatment of tumors.…”

Section: Aiegens For Analysis Of Small Moleculesmentioning

confidence: 99%

Activity‐based smart AIEgens for detection, bioimaging, and therapeutics: Recent progress and outlook

et al. 2021

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Activity‐based approaches for designing AIEgens possess prominent advantages including high selectivity, sensitivity, and signal‐to‐noise ratio, and they have received more attention in recent years. Excellent activatable AIE probes have been reported for detecting toxic substances, imaging intracellular active molecules/biomolecules, as well as monitoring the activity of overexpressed enzymes in cancers. Moreover, the majority of activatable theranostic AIEgens can be specifically triggered in cancer cells and can kill these cells under light irradiation, while they have no distinct effect on normal cells, demonstrating satisfactory therapeutic selectivity that is superior to that of traditional chemotherapy. Thus, in this review, we systematically summarized the development of activatable AIE bioprobes in recent years from molecular design principles to biological applications. The challenges of activatable AIE probes and the corresponding solutions are described. We hope that the information provided in this review will facilitate the design of more activatable AIE probes to promote practical application of corresponding AIEgens.

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A fluorescence and photoactivity dual-activatable prodrug with self-synergistic magnification of the anticancer effect

Abstract: A hydroxycamptothecin prodrug is developed, which can self-report the drug distribution and achieve self-synergistic anticancer efficacy through oxidation therapy.

Cited by 21 publications

References 59 publications

Add the Finishing Touch: Molecular Engineering of Conjugated Small Molecule for High‐Performance AIE Luminogen in Multimodal Phototheranostics

Add the Finishing Touch: Molecular Engineering of Conjugated Small Molecule for High‐Performance AIE Luminogen in Multimodal Phototheranostics

Dual-Targeting Nanoparticle-Mediated Gene Therapy Strategy for Hepatocellular Carcinoma by Delivering Small Interfering RNA

Activity‐based smart AIEgens for detection, bioimaging, and therapeutics: Recent progress and outlook

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