Rational design of a lysosome-targeting and near-infrared absorbing Ru(ii)–BODIPY conjugate for photodynamic therapy

2021 ◽  
Vol 57 (14) ◽  
pp. 1790-1793
Author(s):  
Liping Qiao ◽  
Jiangping Liu ◽  
Yunhong Han ◽  
Fangmian Wei ◽  
Xinxing Liao ◽  
...  

A lysosome-targeting and near-infrared absorbing Ru(ii)–BODIPY conjugate exhibits prominent tumor inhibitory efficiency in malignant melanoma A375 cells and in vivo experiments.

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Yusaku Hontani ◽  
Mikhail Baloban ◽  
Francisco Velazquez Escobar ◽  
Swetta A. Jansen ◽  
Daria M. Shcherbakova ◽  
...  

AbstractNear-infrared fluorescent proteins (NIR FPs) engineered from bacterial phytochromes are widely used for structural and functional deep-tissue imaging in vivo. To fluoresce, NIR FPs covalently bind a chromophore, such as biliverdin IXa tetrapyrrole. The efficiency of biliverdin binding directly affects the fluorescence properties, rendering understanding of its molecular mechanism of major importance. miRFP proteins constitute a family of bright monomeric NIR FPs that comprise a Per-ARNT-Sim (PAS) and cGMP-specific phosphodiesterases - Adenylyl cyclases - FhlA (GAF) domain. Here, we structurally analyze biliverdin binding to miRFPs in real time using time-resolved stimulated Raman spectroscopy and quantum mechanics/molecular mechanics (QM/MM) calculations. Biliverdin undergoes isomerization, localization to its binding pocket, and pyrrolenine nitrogen protonation in <1 min, followed by hydrogen bond rearrangement in ~2 min. The covalent attachment to a cysteine in the GAF domain was detected in 4.3 min and 19 min in miRFP670 and its C20A mutant, respectively. In miRFP670, a second C–S covalent bond formation to a cysteine in the PAS domain occurred in 14 min, providing a rigid tetrapyrrole structure with high brightness. Our findings provide insights for the rational design of NIR FPs and a novel method to assess cofactor binding to light-sensitive proteins.


2021 ◽  
Vol 17 (2) ◽  
pp. 205-215
Author(s):  
Zhenbo Sun ◽  
Mingfang Luo ◽  
Jia Li ◽  
Ailing Wang ◽  
Xucheng Sun ◽  
...  

Imaging-guided cancer theranostic is a promising strategy for cancer diagnostic and therapeutic. Photodynamic therapy (PDT), as an approved treatment modality, is limited by the poor solubility and dispersion of photosensitizers (PS) in biological fluids. Herein, it is demonstrated that superparamagnetic iron oxide (SPIO)-based nanoparticles (SCFs), prepared by conjugated with Chlorin e6 (Ce6) and modified with folic acid (FA) on the surface, can be used as versatile drug delivery vehicles for effective PDT. The nanoparticles are great carriers for photosensitizer Ce6 with an extremely high loading efficiency. In vitro fluorescence imaging and in vivo magnetic resonance imaging (MRI) results indicated that SCFs selectively accumulated in tumor cells. Under near-infrared laser irradiation, SCFs were confirmed to be capable of inducing low cell viability of RM-1 cells In vitro and displaying efficient tumor ablation with negligible side effects in tumor-bearing mice models.


2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Nicola B. van der Walt ◽  
Zahra Zakeri ◽  
Marianne J. Cronjé

Sutherlandia frutescensis a medicinal plant indigenous to Southern Africa and is commonly known as the “cancer bush.” This plant has traditionally been used for the treatment of various ailments, although it is best known for its claims of activity against “internal” cancers. Here we report on its effect on melanoma cells. The aim of this study was to investigate whether an extract ofS. frutescenscould induce apoptosis in the A375 melanoma cell line and to outline the basic mechanism of action.S. frutescensextract induced apoptosis in A375 cells as evidenced by morphological features of apoptosis, phosphatidylserine exposure, nuclear condensation, caspase activation, and the release of cytochromecfrom the mitochondria. Studies in the presence of a pan-caspase inhibitor allude to caspase-independent cell death, which appeared to be mediated by the apoptosis inducing factor. Taken together, the results of this study show thatS. frutescensextract is effective in inducing apoptosis in malignant melanoma cells and indicates that furtherin vivomechanistic studies may be warranted.


2019 ◽  
Vol 116 (41) ◽  
pp. 20296-20302 ◽  
Author(s):  
Zhixuan Zhou ◽  
Jiangping Liu ◽  
Juanjuan Huang ◽  
Thomas W. Rees ◽  
Yiliang Wang ◽  
...  

Photodynamic therapy (PDT) is a treatment procedure that relies on cytotoxic reactive oxygen species (ROS) generated by the light activation of a photosensitizer. The photophysical and biological properties of photosensitizers are vital for the therapeutic outcome of PDT. In this work a 2D rhomboidal metallacycle and a 3D octahedral metallacage were designed and synthesized via the coordination-driven self-assembly of a Ru(II)-based photosensitizer and complementary Pt(II)-based building blocks. The metallacage showed deep-red luminescence, a large 2-photon absorption cross-section, and highly efficient ROS generation. The metallacage was encapsulated into an amphiphilic block copolymer to form nanoparticles to encourage cell uptake and localization. Upon internalization into cells, the nanoparticles selectively accumulate in the lysosomes, a favorable location for PDT. The nanoparticles are almost nontoxic in the dark, and can efficiently destroy tumor cells via the generation of ROS in the lysosomes under 2-photon near-infrared light irradiation. The superb PDT efficacy of the metallacage-containing nanoparticles was further validated by studies on 3D multicellular spheroids (MCS) and in vivo studies on A549 tumor-bearing mice.


2020 ◽  
Vol 63 (17) ◽  
pp. 9950-9964 ◽  
Author(s):  
Zhiliang Yu ◽  
Junliang Zhou ◽  
Xin Ji ◽  
Guangyu Lin ◽  
Shuang Xu ◽  
...  

2021 ◽  
Author(s):  
Haoli Yu ◽  
Yuesong Wang ◽  
Yan Chen ◽  
Min Ji

Purpose: Near-infrared (NIR) fluorescence imaging (FI) become a research hotspot in the field of in vivo imaging. Here, we intend to synthesize a NIR-II fluorescence nano-system with an excellent fluorescence...


2019 ◽  
Vol 11 (17) ◽  
pp. 15417-15425 ◽  
Author(s):  
Qi Yang ◽  
Hongyu Jin ◽  
Yucong Gao ◽  
Jiaomin Lin ◽  
Hong Yang ◽  
...  

2012 ◽  
Vol 52 (4) ◽  
pp. 1175-1179 ◽  
Author(s):  
Ryosuke Kojima ◽  
Hideo Takakura ◽  
Takeaki Ozawa ◽  
Yukio Tada ◽  
Tetsuo Nagano ◽  
...  

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