scholarly journals Precise and Efficient Phototheranostics: Molecular Engineering of Photosensitizers with Near-Infrared Aggregation-Induced Emission for Acid-Triggered Nucleus-Targeted Photodynamic Cancer Therapy

Author(s):  
Zhijun Zhang ◽  
Wenhan XU ◽  
Peihong Xiao ◽  
Miaomiao Kang ◽  
Dingyuan Yan ◽  
...  

Phototheranostics involving both fluorescence imaging (FLI) and photodynamic therapy (PDT) has been recognized to be potentially powerful for cancer treatment by virtue of various intrinsic advantages. However, the state-of-the-art materials in this area are still far from ideal towards practical applications, owing to their respective and collective drawbacks, such as inefficient imaging quality, inferior reactive oxygen species (ROS) production, the lack of subcellular-targeting capability, and dissatisfactory theranostics delivery. In this contribution, these shortcomings are successfully addressed through the integration of finely engineered photosensitizers having aggregation-induced emission (AIE) features and well tailored nanocarrier system. The yielded AIE NPs simultaneously exhibit broad absorption in visible light region, bright near-infrared fluorescence emission, extremely high ROS generation, as well as tumor lysosomal acidity-activated and nucleus-targeted delivery functions, making them dramatically promising for precise and efficient phototheranostics. Both in vitro and in vivo evaluations show that the presented nanotheranostic system bearing excellent photostability and appreciable biosecurity well performed in FLI-guided photodynamic cancer therapy. This study thus not only extends the applications scope of AIE nanomaterials, but also offers useful insights into constructing a new generation of cancer theranostics.

2020 ◽  
Author(s):  
Zhijun Zhang ◽  
Wenhan XU ◽  
Peihong Xiao ◽  
Miaomiao Kang ◽  
Dingyuan Yan ◽  
...  

Phototheranostics involving both fluorescence imaging (FLI) and photodynamic therapy (PDT) has been recognized to be potentially powerful for cancer treatment by virtue of various intrinsic advantages. However, the state-of-the-art materials in this area are still far from ideal towards practical applications, owing to their respective and collective drawbacks, such as inefficient imaging quality, inferior reactive oxygen species (ROS) production, the lack of subcellular-targeting capability, and dissatisfactory theranostics delivery. In this contribution, these shortcomings are successfully addressed through the integration of finely engineered photosensitizers having aggregation-induced emission (AIE) features and well tailored nanocarrier system. The yielded AIE NPs simultaneously exhibit broad absorption in visible light region, bright near-infrared fluorescence emission, extremely high ROS generation, as well as tumor lysosomal acidity-activated and nucleus-targeted delivery functions, making them dramatically promising for precise and efficient phototheranostics. Both in vitro and in vivo evaluations show that the presented nanotheranostic system bearing excellent photostability and appreciable biosecurity well performed in FLI-guided photodynamic cancer therapy. This study thus not only extends the applications scope of AIE nanomaterials, but also offers useful insights into constructing a new generation of cancer theranostics.


2020 ◽  
Author(s):  
Zhijun Zhang ◽  
Wenhan XU ◽  
Peihong Xiao ◽  
Miaomiao Kang ◽  
Dingyuan Yan ◽  
...  

Phototheranostics involving both fluorescence imaging (FLI) and photodynamic therapy (PDT) has been recognized to be potentially powerful for cancer treatment by virtue of various intrinsic advantages. However, the state-of-the-art materials in this area are still far from ideal towards practical applications, owing to their respective and collective drawbacks, such as inefficient imaging quality, inferior reactive oxygen species (ROS) production, the lack of subcellular-targeting capability, and dissatisfactory theranostics delivery. In this contribution, these shortcomings are successfully addressed through the integration of finely engineered photosensitizers having aggregation-induced emission (AIE) features and well tailored nanocarrier system. The yielded AIE NPs simultaneously exhibit broad absorption in visible light region, bright near-infrared fluorescence emission, extremely high ROS generation, as well as tumor lysosomal acidity-activated and nucleus-targeted delivery functions, making them dramatically promising for precise and efficient phototheranostics. Both in vitro and in vivo evaluations show that the presented nanotheranostic system bearing excellent photostability and appreciable biosecurity well performed in FLI-guided photodynamic cancer therapy. This study thus not only extends the applications scope of AIE nanomaterials, but also offers useful insights into constructing a new generation of cancer theranostics.


Nanomaterials ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1947
Author(s):  
Wei-Jane Chiu ◽  
Yi-Chun Chen ◽  
Chih-Ching Huang ◽  
Lingyan Yang ◽  
Jiantao Yu ◽  
...  

Minimal invasive phototherapy utilising near-infrared (NIR) laser to generate local reactive oxygen species (ROS) and heat has few associated side effects and is a precise treatment in cancer therapy. However, high-efficiency and safe phototherapeutic tumour agents still need developing. The application of iron hydroxide/oxide immobilised on reduced graphene oxide (FeOxH–rGO) nanocomposites as a therapeutic agent in integration photodynamic cancer therapy (PDT) and photothermal cancer therapy (PTT) was discussed. Under 808 nm NIR irradiation, FeOxH–rGO offers a high ROS generation and light-to-heat conversion efficiency because of its strong NIR absorption. These phototherapeutic effects lead to irreversible damage in FeOxH–rGO-treated T47D cells. Using a tumour-bearing mouse model, NIR ablated the breast tumour effectively in the presence of FeOxH–rGO. The tumour treatment response was evaluated to be 100%. We integrated PDT and PTT into a single nanodevice to facilitate effective cancer therapy. Our FeOxH–rGO, which integrates the merits of FeOxH and rGO, displays an outstanding tumoricidal capacity, suggesting the utilization of this nanocomposites in future medical applications.


2020 ◽  
Vol 4 (7) ◽  
pp. 2064-2071 ◽  
Author(s):  
Hanxiao Yang ◽  
Jiabao Zhuang ◽  
Nan Li ◽  
Yue Li ◽  
Shiyu Zhu ◽  
...  

A highly efficient near-infrared photosensitizer with aggregation-induced emission characteristics was developed for mitochondria-targeted and image-guided photodynamic cancer therapy.


2016 ◽  
Vol 6 (1) ◽  
Author(s):  
S. Shashank Chetty ◽  
S. Praneetha ◽  
Sandeep Basu ◽  
Chetana Sachidanandan ◽  
A. Vadivel Murugan

Abstract Near-infrared (NIR) luminescent CuInS2-ZnS alloyed nanocrystals (CIZS-NCs) for highly fluorescence bioimaging have received considerable interest in recent years. Owing, they became a desirable alternative to heavy-metal based-NCs and organic dyes with unique optical properties and low-toxicity for bioimaging and optoelectronic applications. In the present study, bright and robust CIZS-NCs have been synthesized within 5 min, as-high-as 230 °C without requiring any inert-gas atmosphere via microwave-solvothermal (MW-ST) method. Subsequently, the in vitro and in vivo nano-xenotoxicity and cellular uptake of the MUA-functionalized CIZS-NCs were investigated in L929, Vero, MCF7 cell lines and zebrafish-embryos. We observed minimal toxicity and acute teratogenic consequences upto 62.5 μg/ml of the CIZS-NCs in zebrafish-embryos. We also observed spontaneous uptake of the MUA-functionalized CIZS-NCs by 3 dpf older zebrafish-embryos that are evident through bright red fluorescence-emission at a low concentration of 7.8 μg/mL. Hence, we propose that the rapid, low-cost, large-scale “sustainable” MW-ST synthesis of CIZS-NCs, is an ideal bio-nanoprobe with good temporal and spatial resolution for rapid labeling, long-term in vivo tracking and intravital-fluorescence-bioimaging (IVBI).


Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1110
Author(s):  
Blerina Shkodra ◽  
Adrian T. Press ◽  
Antje Vollrath ◽  
Ivo Nischang ◽  
Stephanie Schubert ◽  
...  

Bisindolylmaleimide I (BIM-I) is a competitive pan protein kinase C inhibitor with anti-inflammatory and anti-metastatic properties, suggested to treat inflammatory diseases and various cancer entities. However, despite its therapeutic potential, BIM-I has two major drawbacks, i.e., it has a poor water solubility, and it binds the human ether-à-go-go-related gene (hERG) ion channels, potentially causing deadly arrhythmias. In this case, a targeted delivery of BIM-I is imperative to minimize peripheral side effects. To circumvent these drawbacks BIM-I was encapsulated into nanoparticles prepared from poly(lactic-co-glycolic acid) (PLGA) functionalized by the near-infrared dye DY-635. DY-635 served as an active targeting moiety since it selectively binds the OATP1B1 and OATP1B3 transporters that are highly expressed in liver and cancer cells. PLGA-DY-635 (BIM-I) nanoparticles were produced by nanoprecipitation and characterized using dynamic light scattering, analytical ultracentrifugation, and cryogenic transmission electron microscopy. Particle sizes were found to be in the range of 20 to 70 nm, while a difference in sizes between the drug-loaded and unloaded particles was observed by all analytical techniques. In vitro studies demonstrated that PLGA-DY-635 (BIM-I) NPs prevent the PKC activation efficiently, proving the efficacy of the inhibitor after its encapsulation, and suggesting that BIM-I is released from the PLGA-NPs. Ultimately, our results present a feasible formulation strategy that improved the cytotoxicity profile of BIM-I and showed a high cellular uptake in the liver as demonstrated in vivo by intravital microscopy investigations.


2020 ◽  
Vol 8 ◽  
Author(s):  
Elisa Carrasco ◽  
Juan Carlos Stockert ◽  
Ángeles Juarranz ◽  
Alfonso Blázquez-Castro

For decades, the possibility to generate Reactive Oxygen Species (ROS) in biological systems through the use of light was mainly restricted to the photodynamic effect: the photoexcitation of molecules which then engage in charge- or energy-transfer to molecular oxygen (O2) to initiate ROS production. However, the classical photodynamic approach presents drawbacks, like per se chemical reactivity of the photosensitizing agent or fast molecular photobleaching due to in situ ROS generation, to name a few. Recently, a new approach, which promises many advantages, has entered the scene: plasmon-driven hot-electron chemistry. The effect takes advantage of the photoexcitation of plasmonic resonances in metal nanoparticles to induce a new cohort of photochemical and redox reactions. These metal photo-transducers are considered chemically inert and can undergo billions of photoexcitation rounds without bleaching or suffering significant oxidative alterations. Also, their optimal absorption band can be shape- and size-tailored in order to match any of the near infrared (NIR) biological windows, where undesired absorption/scattering are minimal. In this mini review, the basic mechanisms and principal benefits of this light-driven approach to generate ROS will be discussed. Additionally, some significant experiments in vitro and in vivo will be presented, and tentative new avenues for further research will be advanced.


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