scholarly journals A self-assembled Ru–Pt metallacage as a lysosome-targeting photosensitizer for 2-photon photodynamic therapy

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.

2018 ◽  
Vol 115 (22) ◽  
pp. 5664-5669 ◽  
Author(s):  
Zhixuan Zhou ◽  
Jiangping Liu ◽  
Thomas W. Rees ◽  
Heng Wang ◽  
Xiaopeng Li ◽  
...  

As an effective and noninvasive treatment of various diseases, photodynamic therapy (PTD) relies on the combination of light, a photosensitizer, and oxygen to generate cytotoxic reactive oxygen species that can damage malignant tissue. Much attention has been paid to covalent modifications of the photosensitizers to improve their photophysical properties and to optimize the pathway of the photosensitizers interacting with cells within the target tissue. Herein we report the design and synthesis of a supramolecular heterometallic Ru–Pt metallacycle via coordination-driven self-assembly. While inheriting the excellent photostability and two-photon absorption characteristics of the Ru(II) polypyridyl precursor, the metallacycle also exhibits red-shifted luminescence to the near-infrared region, a larger two-photon absorption cross-section, and higher singlet oxygen generation efficiency, making it an excellent candidate as a photosensitizer for PTD. Cellular studies reveal that the metallacycle selectively accumulates in mitochondria and nuclei upon internalization. As a result, singlet oxygen generated by photoexcitation of the metallacycle can efficiently trigger cell death via the simultaneous damage to mitochondrial function and intranuclear DNA. In vivo studies on tumor-bearing mice show that the metallacycle can efficiently inhibit tumor growth under a low light dose with minimal side effects. The supramolecular approach presented in this work provides a paradigm for the development of PDT agents with high efficacy.


2020 ◽  
Vol 6 (44) ◽  
pp. eabb6165
Author(s):  
Lukas Pfeifer ◽  
Nong V. Hoang ◽  
Maximilian Scherübl ◽  
Maxim S. Pshenichnikov ◽  
Ben L. Feringa

Light-controlled artificial molecular machines hold tremendous potential to revolutionize molecular sciences as autonomous motion allows the design of smart materials and systems whose properties can respond, adapt, and be modified on command. One long-standing challenge toward future applicability has been the need to develop methods using low-energy, low-intensity, near-infrared light to power these nanomachines. Here, we describe a rotary molecular motor sensitized by a two-photon absorber, which efficiently operates under near-infrared light at intensities and wavelengths compatible with in vivo studies. Time-resolved spectroscopy was used to gain insight into the mechanism of energy transfer to the motor following initial two-photon excitation. Our results offer prospects toward in vitro and in vivo applications of artificial molecular motors.


Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 274 ◽  
Author(s):  
Esteban Colombo ◽  
Antonio Signore ◽  
Stefano Aicardi ◽  
Angelina Zekiy ◽  
Anatoliy Utyuzh ◽  
...  

Background: Under physiological conditions, endothelial cells are the main regulator of arterial tone homeostasis and vascular growth, sensing and transducing signals between tissue and blood. Disease risk factors can lead to their unbalanced homeostasis, known as endothelial dysfunction. Red and near-infrared light can interact with animal cells and modulate their metabolism upon interaction with mitochondria’s cytochromes, which leads to increased oxygen consumption, ATP production and ROS, as well as to regulate NO release and intracellular Ca2+ concentration. This medical subject is known as photobiomodulation (PBM). We present a review of the literature on the in vitro and in vivo effects of PBM on endothelial dysfunction. Methods: A search strategy was developed consistent with the PRISMA statement. The PubMed, Scopus, Cochrane, and Scholar electronic databases were consulted to search for in vitro and in vivo studies. Results: Fifty out of >12,000 articles were selected. Conclusions: The PBM can modulate endothelial dysfunction, improving inflammation, angiogenesis, and vasodilatation. Among the studies, 808 nm and 18 J (0.2 W, 2.05 cm2) intracoronary irradiation can prevent restenosis as well as 645 nm and 20 J (0.25 W, 2 cm2) can stimulate angiogenesis. PBM can also support hypertension cure. However, more extensive randomised controlled trials are necessary.


2021 ◽  
Author(s):  
Xue Wang ◽  
Lili Xuan ◽  
Ying Pan

Melanoma is one of the deadliest forms of cancer, for which therapeutic regimens are usually limited by the development of resistance. Here, we fabricated the Fe3O4 nanoparticle clusters (NPCs) that have drawn widespread attention and investigated their role in the treatment of melanoma by photothermal therapy (PTT). Transmission electron microscopy imaging shows that our synthesized NPCs are spherically shaped with an averaged diameter of 329.2 nm. They are highly absorptive at the near-infrared 808 nm wavelength and efficient at converting light into local heat. In vitro experiments using light-field microscopy and MTT assay showed that Fe3O4 NPCs, in conjunction with near-infrared irradiation, effectively ablated A375 melanoma cells by inducing overt apoptosis. Consistently, in vivo studies using BALB/c mice found that intratumoral administration of Fe3O4 NPCs and concomitant in situ exposure to near-infrared light significantly inhibited growth of implanted tumor xenografts. Finally, we revealed, by experimental approaches including semi-quantitative PCR, western blot and immunohistochemistry, the heat shock protein HSP70 to be upregulated in response to PTT, suggesting this chaperone protein could be a plausible underlying mechanism for the observed therapeutic outcome. Altogether, our results highlight the promise of Fe3O4 NPCs as a new PTT option to treat melanoma.


2012 ◽  
Vol 22 (11) ◽  
pp. 4861 ◽  
Author(s):  
Sisi Cui ◽  
Haiyan Chen ◽  
Hongyan Zhu ◽  
Junmei Tian ◽  
Xuemei Chi ◽  
...  

ACS Nano ◽  
2012 ◽  
Vol 7 (1) ◽  
pp. 676-688 ◽  
Author(s):  
Sisi Cui ◽  
Deyan Yin ◽  
Yuqi Chen ◽  
Yingfeng Di ◽  
Haiyan Chen ◽  
...  

ACS Nano ◽  
2015 ◽  
Vol 9 (3) ◽  
pp. 2584-2599 ◽  
Author(s):  
Zhiyao Hou ◽  
Yuanxin Zhang ◽  
Kerong Deng ◽  
Yinyin Chen ◽  
Xuejiao Li ◽  
...  

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Gutian Zhang ◽  
Wenting Cheng ◽  
Lin Du ◽  
Chuanjun Xu ◽  
Jinlong Li

Abstract Background Phototherapy is a promising strategy for cancer therapy by reactive oxygen species (ROS) of photodynamic therapy (PDT) and hyperthermia of photothermal therapy (PTT). However, the therapeutic efficacy was restricted by tumor hypoxia and thermal resistance of increased expression of heat shock protein (Hsp). In this study, we developed albumin nanoparticles to combine hypoxia relief and heat shock protein inhibition to overcome these limitations for phototherapy enhancement. Results Near-infrared photosensitizer (IR780) and gambogic acid (GA, Hsp90 inhibitor) were encapsulated into albumin nanoparticles via hydrophobic interaction, which was further deposited MnO2 on the surface to form IGM nanoparticles. Both in vitro and in vivo studies demonstrated that IGM could catalyze overexpress of hydrogen peroxide to relive hypoxic tumor microenvironment. With near infrared irradiation, the ROS generation was significantly increase for PDT enhancement. In addition, the release of GA was promoted by irradiation to bind with Hsp90, which could reduce cell tolerance to heat for PTT enhancement. As a result, IGM could achieve better antitumor efficacy with enhanced PDT and PTT. Conclusion This study develops a facile approach to co-deliver IR780 and GA with self-assembled albumin nanoparticles, which could relive hypoxia and suppress Hsp for clinical application of cancer phototherapy.


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