Comparative Studies of the Cellular Uptake, Subcellular Localization, and Cytotoxic and Phototoxic Antitumor Properties of Ruthenium(II)–Porphyrin Conjugates with Different Linkers

Zhang, Jingxiang; Zhou, Junwei; Chan, Chi Fai; Lau, Terrence Chi-Kong; Kwong, Daniel W. J.; Tam, Hoi Lam; Mak, Nai‐Ki; Wong, Ka‐Leung; Wong, Wai‐Kwok

doi:10.1021/bc300201h

Cited by 89 publications

(51 citation statements)

References 61 publications

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“…Most simple functionalizations of porphyrins lead only to improvement of the lipid/water partition coefficient and have to be accompanied by a fine-tuning of photophysical properties in order to optimize the reactive oxygen species generation and absorption properties.4.1.2 Insertion of metal complexes as macrocycle substituentsAn entirely different approach for peripheral modification of porphyrins involves the insertion of metal complexes as macrocycle substituents. An interesting study reported polypyridyl Ru(II) complexes as peripheral substituents of porphyrins[134][135][136][137][138]. The benefit expected from this type of Ru complexes is the enhancement of two-photon absorption (2PA) of sensitizers.…”

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confidence: 99%

“…2PA involves a simultaneous interaction of two-photons with the photosensitizer.Coupling with a strong charge-transfer chromophore increases the 2PA of sensitizers.Amphiphilic porphyrins with the attached Ru polypyridyl complexes, where charge separation occurs, have enhanced 2PA cross sections. Recently, a series of porphyrin-Ru(II) polypyridyl complexes conjugates have been studied as potential bifunctional probes for two-photon (NIR) tumor-imaging and photodynamic therapeutic agents[134,135]. This type of a linkage between hydrophobic and hydrophilic moieties is an important parameter to consider in designing the porphyrin-Ru(II) conjugates.…”

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confidence: 99%

“…The series of six water-soluble free-base porphyrin-Ru(II) conjugates, and Zn(II) porphyrin-Ru(II) conjugates with different linkers were synthesized(Fig. 12) and extensively studied[135]. The emission quantum yields of free base conjugates are strongly influenced by the length and conjugation of the linker between the porphyrin moiety and the [Ru(bpy) 2 (phen)] 2+ complex.…”

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confidence: 99%

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Engineering of relevant photodynamic processes through structural modifications of metallotetrapyrrolic photosensitizers

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Engineering of relevant photodynamic processes through structural modifications of metallotetrapyrrolic photosensitizers

Dąbrowski

Pucelik

Regiel-Futyra

et al. 2016

Coordination Chemistry Reviews

233

185

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“…Several design strategies for TPA-PDT photosensitizers have been reported in the literature, but only very few of those compounds are tumor cell-specific or have been investigated in vitro and in vivo, concerning especially porphyrins and lanthanides (6). For instance, selective closure of blood vessels through two-photon excitation PDT in vivo using porphyrin dimers of large TP absorption cross-section has been demonstrated currently (7); tumor selectivity of amphiphilic photosensitizers has also been found related to their efficient binding to low-density lipoproteins, which are responsible for the transport of porphyrins to tumor tissues (8,9). High-molecular-weight porphyrins, in essence, preferentially accumulate on solid tumors and are expected to be internalized into membrane-limited organelles, thereby achieving controlled localization in the intercellular compartment (10).…”

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confidence: 99%

In vivo selective cancer-tracking gadolinium eradicator as new-generation photodynamic therapy agent

Zhang

Lan

Chan

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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In this work, we demonstrate a modality of photodynamic therapy (PDT) through the design of our truly dual-functional-PDT and imaging-gadolinium complex (Gd-N), which can target cancer cells specifically. In the light of our design, the PDT drug can specifically localize on the anionic cell membrane of cancer cells in which its laser-excited photoemission signal can be monitored without triggering the phototoxic generation of reactive oxygen species-singlet oxygen-before due excitation. Comprehensive in vitro and in vivo studies had been conducted for the substantiation of the effectiveness of Gd-N as such a tumor-selective PDT photosensitizer. This treatment modality does initiate a new direction in the development of "precision medicine" in line with stem cell and gene therapies as tools in cancer therapy.ignificant challenges of tumor cells recognition, in-depth light penetration, and in situ monitoring are confronted by scientists to develop photodynamic therapy (PDT) as a reliable clinical treatment for cancers (1, 2). To address the penetration depth and molecular imaging issues, the utilization of nearinfrared (NIR) excitation (via multiphoton/up-conversion processes) and emission within the "biological windows" (such as first window: 600-950 nm; second window: 1-1.35 μm; and third window: 1.5-1.8 μm) (3) has provided a satisfying resolution because NIR photons can penetrate deep into the tissue and reemit sharply without being absorbed by the cell even in the blood media and causing damage. Clear images can be obtained and differentiated then from the usual biological autofluorescence background (4). Recently, two-photon absorption photodynamic therapy (TPA-PDT) has received increasing attention (5). Porphyrin-based photosensitizers are considered as the prime candidates as their two-photon (TP)-induced singlet oxygen ( 1 O 2 ) generation and red/NIR emission (∼650 and ∼750 nm) are very efficient and intense. Several design strategies for TPA-PDT photosensitizers have been reported in the literature, but only very few of those compounds are tumor cell-specific or have been investigated in vitro and in vivo, concerning especially porphyrins and lanthanides (6). For instance, selective closure of blood vessels through two-photon excitation PDT in vivo using porphyrin dimers of large TP absorption cross-section has been demonstrated currently (7); tumor selectivity of amphiphilic photosensitizers has also been found related to their efficient binding to low-density lipoproteins, which are responsible for the transport of porphyrins to tumor tissues (8, 9). High-molecular-weight porphyrins, in essence, preferentially accumulate on solid tumors and are expected to be internalized into membrane-limited organelles, thereby achieving controlled localization in the intercellular compartment (10). However, it has still been arduous for PDT probes to come into contact with cancer cells in particular, with two major problems being associated with commercially available or literature-reporting photosensitizers for ph...

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“…Porphyrins or porphyrin-like compounds are the agents of choice in most approaches to SDT, because they can accumulate in rapidly growing tissues, including tumors and atherosclerotic plaques. 15,16 Protoporphyrin IX (PpIX) is known to be a component of hematoporphyrin. Our previous research showed that selective accumulation of PpIX in atherosclerotic plaque was 12 times higher than in normal vessel walls, 17 indicating the possibility of an atherosclerosis-selective therapeutic agent.…”

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confidence: 99%

Apoptosis of THP-1 macrophages induced by protoporphyrin IX-mediated sonodynamic therapy

Guo¹,

Sun²,

Cheng³

et al. 2013

IJN

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Background: Sonodynamic therapy (SDT) was developed as a localized ultrasound-activated cytotoxic therapy for cancer. The ability of SDT to destroy target tissues selectively is especially appealing for atherosclerotic plaque, in which selective accumulation of the sonosensitizer, protoporphyrin IX (PpIX), had been demonstrated. Here we investigate the effects of PpIXmediated SDT on macrophages, which are the main culprit in progression of atherosclerosis. Methods and results: Cultured THP-1 derived macrophages were incubated with PpIX. Fluorescence microscopy showed that the intracellular PpIX concentration increased with the concentration of PpIX in the incubation medium. MTT assay demonstrated that SDT with PpIX significantly decreased cell viability, and this effect increased with duration of ultrasound exposure and PpIX concentration. PpIX-mediated SDT induced both apoptosis and necrosis, and the maximum apoptosis to necrosis ratio was obtained after SDT with 20 µg/mL PpIX and five minutes of sonication. Production of intracellular singlet oxygen and secondary disruption of the cytoskeleton were also observed after SDT with PpIX. Conclusion: PpIX-mediated SDT had apoptotic effects on THP-1 macrophages via generation of intracellular singlet oxygen and disruption of the cytoskeleton. PpIX-mediated SDT may be a potential treatment to attenuate progression of atherosclerotic plaque.

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Comparative Studies of the Cellular Uptake, Subcellular Localization, and Cytotoxic and Phototoxic Antitumor Properties of Ruthenium(II)–Porphyrin Conjugates with Different Linkers

Cited by 89 publications

References 61 publications

Engineering of relevant photodynamic processes through structural modifications of metallotetrapyrrolic photosensitizers

Engineering of relevant photodynamic processes through structural modifications of metallotetrapyrrolic photosensitizers

In vivo selective cancer-tracking gadolinium eradicator as new-generation photodynamic therapy agent

Apoptosis of THP-1 macrophages induced by protoporphyrin IX-mediated sonodynamic therapy

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