Multifunctional AIE iridium (III) photosensitizer nanoparticles for two-photon-activated imaging and mitochondria targeting photodynamic therapy

AbstractDeveloping novel photosensitizers for deep tissue imaging and efficient photodynamic therapy (PDT) remains a challenge because of the poor water solubility, low reactive oxygen species (ROS) generation efficiency, serve dark cytotoxicity, and weak absorption in the NIR region of conventional photosensitizers. Herein, cyclometalated iridium (III) complexes (Ir) with aggregation-induced emission (AIE) feature, high photoinduced ROS generation efficiency, two-photon excitation, and mitochondria-targeting capability were designed and further encapsulated into biocompatible nanoparticles (NPs). The Ir-NPs can be used to disturb redox homeostasis in vitro, result in mitochondrial dysfunction and cell apoptosis. Importantly, in vivo experiments demonstrated that the Ir-NPs presented obviously tumor-targeting ability, excellent antitumor effect, and low systematic dark-toxicity. Moreover, the Ir-NPs could serve as a two-photon imaging agent for deep tissue bioimaging with a penetration depth of up to 300 μm. This work presents a promising strategy for designing a clinical application of multifunctional Ir-NPs toward bioimaging and PDT.

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Multifunctional AIE Iridium (III) Photosensitizer Nanoparticles for Two-Photon-Activated Imaging and Mitochondria Targeting Photodynamic Therapy

10.21203/rs.3.rs-638211/v1 ◽

2021 ◽

Author(s):

Xuzi Cai ◽

Kangnan Wang ◽

Wen Ma ◽

yuanyuan Yang ◽

Gui Chen ◽

...

Keyword(s):

Photodynamic Therapy ◽

Water Solubility ◽

Redox Homeostasis ◽

Tissue Imaging ◽

Ros Generation ◽

Generation Efficiency ◽

Deep Tissue ◽

Two Photon ◽

Targeting Ability

Abstract Developing novel photosensitizers for deep tissue imaging and efficient photodynamic therapy (PDT) remains a challengebecause of the poor water solubility, low reactive oxygen species (ROS) generation efficiency, serve dark cytotoxicity, and weak absorption in the NIR region of conventional photosensitizers. Herein,cyclometalated iridium (III) complexes(Ir)with aggregation-induced emission (AIE) feature, high photoinduced ROS generation efficiency, two-photonexcitation, and mitochondria-targetingcapability were designed and further encapsulated into biocompatible nanoparticles (NPs).The Ir-NPs can be used to disturb redox homeostasis in vitro, result in mitochondrial dysfunction and cell apoptosis. Importantly, invivo experiments demonstrated that theIr-NPs presented obviously tumor-targeting ability, excellent antitumor effect, and low systematic dark-toxicity. Moreover, the Ir-NPs could serve as a two-photon imaging agent for deep tissue bioimaging with a penetration depth of up to 300 μm. This work presents a promising strategy for designing a clinical application of multifunctional Ir-NPs toward bioimaging and PDT.

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NIR Photosensitizer for Two-Photon Fluorescent Imaging and Photodynamic Therapy of Tumor

Frontiers in Chemistry ◽

10.3389/fchem.2021.629062 ◽

2021 ◽

Vol 9 ◽

Author(s):

Lujia Chen ◽

Meijuan Chen ◽

Yuping Zhou ◽

Changsheng Ye ◽

Ruiyuan Liu

Keyword(s):

Photodynamic Therapy ◽

Near Infrared ◽

Fluorescent Imaging ◽

Deep Tissue ◽

Two Photon ◽

Nir Emission ◽

Good Biocompatibility ◽

Fluorescent Agent

Preparation of near-infrared (NIR) emissive fluorophore for imaging-guided PDT (photodynamic therapy) has attracted enormous attention. Hence, NIR photosensitizers of two-photon (TP) fluorescent imaging and photodynamic therapy are highly desirable. In this contribution, a novel D-π-A structured NIR photosensitizer (TTRE) is synthesized. TTRE demonstrates near-infrared (NIR) emission, good biocompatibility, and superior photostability, which can act as TP fluorescent agent for clear visualization of cells and vascular in tissue with deep-tissue penetration. The PDT efficacy of TTRE as photosensitizer is exploited in vitro and in vivo. All these results confirm that TTRE would serve as potential platform for TP fluorescence imaging and imaging-guided photodynamic therapy.

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Ultrabright red AIEgens for two-photon vascular imaging with high resolution and deep penetration

Chemical Science ◽

10.1039/c7sc04820c ◽

2018 ◽

Vol 9 (10) ◽

pp. 2705-2710 ◽

Cited By ~ 46

Author(s):

Wei Qin ◽

Pengfei Zhang ◽

Hui Li ◽

Jacky W. Y. Lam ◽

Yuanjing Cai ◽

...

Keyword(s):

High Resolution ◽

Vascular Imaging ◽

Tissue Imaging ◽

Deep Penetration ◽

High Contrast ◽

Deep Tissue ◽

Two Photon ◽

High Penetration ◽

Deep Tissue Imaging

A successful strategy for the design of ultrabright red luminogens with aggregation-induced emission (AIE) features is reported. The AIE dots can be utilized as efficient fluorescent probes for in vivo deep-tissue imaging with high penetration depth and high contrast.

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Use of Cyclodextrins in Anticancer Photodynamic Therapy Treatment

Molecules ◽

10.3390/molecules23081936 ◽

2018 ◽

Vol 23 (8) ◽

pp. 1936 ◽

Cited By ~ 18

Author(s):

Amina Ben Mihoub ◽

Ludivine Larue ◽

Albert Moussaron ◽

Zahraa Youssef ◽

Ludovic Colombeau ◽

...

Keyword(s):

Drug Delivery ◽

Photodynamic Therapy ◽

Molecular Oxygen ◽

Inclusion Complexes ◽

Water Solubility ◽

Cellular Damage ◽

Hybrid Nanoparticles ◽

Binding Modes

Photodynamic therapy (PDT) is mainly used to destroy cancerous cells; it combines the action of three components: a photoactivatable molecule or photosensitizer (PS), the light of an appropriate wavelength, and naturally occurring molecular oxygen. After light excitation of the PS, the excited PS then reacts with molecular oxygen to produce reactive oxygen species (ROS), leading to cellular damage. One of the drawbacks of PSs is their lack of solubility in water and body tissue fluids, thereby causing low bioavailability, drug-delivery efficiency, therapeutic efficacy, and ROS production. To improve the water-solubility and/or drug delivery of PSs, using cyclodextrins (CDs) is an interesting strategy. This review describes the in vitro or/and in vivo use of natural and derived CDs to improve antitumoral PDT efficiency in aqueous media. To achieve these goals, three types of binding modes of PSs with CDs are developed: non-covalent CD–PS inclusion complexes, covalent CD–PS conjugates, and CD–PS nanoassemblies. This review is divided into three parts: (1) non-covalent CD-PS inclusion complexes, covalent CD–PS conjugates, and CD–PS nanoassemblies, (2) incorporating CD–PS systems into hybrid nanoparticles (NPs) using up-converting or other types of NPs, and (3) CDs with fullerenes as PSs.

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Lysosome-targetable polythiophene nanoparticles for two-photon excitation photodynamic therapy and deep tissue imaging

Journal of Materials Chemistry B ◽

10.1039/c7tb00371d ◽

2017 ◽

Vol 5 (20) ◽

pp. 3651-3657 ◽

Cited By ~ 25

Author(s):

Shaojing Zhao ◽

Guangle Niu ◽

Feng Wu ◽

Li Yan ◽

Hongyan Zhang ◽

...

Keyword(s):

Photodynamic Therapy ◽

Quantum Yield ◽

Fluorescence Imaging ◽

Cross Section ◽

Tissue Imaging ◽

Deep Tissue ◽

Two Photon ◽

Photon Excitation ◽

Deep Tissue Imaging ◽

Two Photon Excitation

Polythiophene nanoparticles with large TPA cross section and high1O2generation quantum yield have been developed for simultaneous lysosome-targetable fluorescence imaging and photodynamic therapy.

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Redox-Sensitive and Folate-Receptor-Mediated Targeting of Cervical Cancer Cells for Photodynamic Therapy Using Nanophotosensitizers Composed of Chlorin e6-Conjugated β-Cyclodextrin via Diselenide Linkage

Cells ◽

10.3390/cells10092190 ◽

2021 ◽

Vol 10 (9) ◽

pp. 2190

Author(s):

Howard Kim ◽

Mi Woon Kim ◽

Young-IL Jeong ◽

Hoe Saeng Yang

Keyword(s):

Cervical Cancer ◽

Photodynamic Therapy ◽

Hela Cells ◽

Folate Receptor ◽

Chlorin E6 ◽

Ros Generation ◽

Cervical Cancer Cells ◽

Poly Ethylene

The aim of this study was to fabricate a reactive oxygen species (ROS)-sensitive and folate-receptor-targeted nanophotosensitizer for the efficient photodynamic therapy (PDT) of cervical carcinoma cells. Chlorin e6 (Ce6) as a model photosensitizer was conjugated with succinyl β-cyclodextrin via selenocystamine linkages. Folic acid (FA)-poly(ethylene glycol) (PEG) (FA-PEG) conjugates were attached to these conjugates and then FA-PEG-succinyl β-cyclodextrin-selenocystamine-Ce6 (FAPEGbCDseseCe6) conjugates were synthesized. Nanophotosensitizers of FaPEGbCDseseCe6 conjugates were fabricated using dialysis membrane. Nanophotosensitizers showed spherical shapes with small particle sizes. They were disintegrated in the presence of hydrogen peroxide (H2O2) and particle size distribution changed from monomodal distribution pattern to multimodal pattern. The fluorescence intensity and Ce6 release rate also increased due to the increase in H2O2 concentration, indicating that the nanophotosensitizers displayed ROS sensitivity. The Ce6 uptake ratio, ROS generation and cell cytotoxicity of the nanophotosensitizers were significantly higher than those of the Ce6 itself against HeLa cells in vitro. Furthermore, the nanophotosensitizers showed folate-receptor-specific delivery capacity and phototoxicity. The intracellular delivery of nanophotosensitizers was inhibited by folate receptor blocking, indicating that they have folate-receptor specificity in vitro and in vivo. Nanophotosensitizers showed higher efficiency in inhibition of tumor growth of HeLa cells in vivo compared to Ce6 alone. These results show that nanophotosensitizers of FaPEGbCDseseCe6 conjugates are promising candidates as PDT of cervical cancer.

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Lactose-conjugated porphyrin: Synthesis and photobiological evaluation as potential agents for photodynamic therapy

Canadian Journal of Chemistry ◽

10.1139/cjc-2021-0030 ◽

2021 ◽

Author(s):

Yue Cao ◽

Xin Zhang ◽

Bo Ren ◽

Xiaodong Yang

Keyword(s):

Photodynamic Therapy ◽

Water Solubility ◽

Application Range ◽

Porphyrin Derivatives ◽

The Poor ◽

Specific Cytotoxicity ◽

Tumor Selectivity ◽

Porphyrin Synthesis

Porphyrin-based photosensitizers are conventional photodynamic agents applied in clinic. However, their clinic application has been overshadowed by the poor water solubility. In addition, they have weak tumor selectivity, which may cause undesirable side effects. The preparation of novel porphyrin derivatives has been explored for the potential application in photodynamic therapy (PDT). To achieve this goal, lactose-conjugated porphyrin nanoparticles (Lac-PorNPs) has been synthesized and characterized. PDT with Lac-PorNPs exhibits tumor-specific cytotoxicity in lactose receptor overexpressed HepG2 cells in vitro and in vivo. In summary, we designed and synthesized lactose conjugates porphyrin with enhanced water-solubility and tumor selectivity. This work expanded the application range of porphyrin-based photosensitizers for cancer treatment.

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