Recent Advances in the Design of Targeted Iridium(III) Photosensitizers for Photodynamic Therapy

Huang, Huaiyi; Banerjee, Samya; Sadler, Peter J.

doi:10.1002/cbic.201800182

Cited by 170 publications

(123 citation statements)

References 73 publications

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“…Another advantage of introducing a non‐essential metal is that it can allow quantification and localization of the photosensitizer in cells and tissues by a variety of techniques, including X‐ray absorption spectroscopy (XAS) and inductively coupled plasma‐mass spectrometry (ICP‐MS). Furthermore, if the metal complexes are luminescent, their cellular localization can often be precisely determined by confocal microscopy …”

Section: Pdt Agentsmentioning

confidence: 99%

“…Furthermore, if the metal complexes are luminescent, their cellular localization can often be precisely determined by confocal microscopy. [8] Ruthenium(II) polypyridyl complexes, including TLD1433 (4; Figure 1), the first metal-based photosensitizer without a tetrapyrrolic moiety to enter clinical trials for nonmuscle invasive bladder cancer PDT (ClinicalTrials.gov, identifier NCT03053635), [6] are attracting significant attention as PDT photosensitizers, as are luminescent polypyridyl complexes of Ir III , Os II and Re I . [9] In the next sections, we present examples of promising new photosensitizers and consider in more detail their mechanism of action, with particular focus on their interaction with proteins upon irradiation.…”

Section: Pdt Agentsmentioning

confidence: 99%

“…Because photoactivatable molecules exert their therapeutic action via excited states, the mechanism of action is often significantly different from traditional chemotherapeutics and less subject to cross‐resistance with existing pharmaceuticals . This potential of photoactivatable therapeutics, combined with the development of laser‐ and LED‐based technologies for effective delivery of light to different tissues, has led to the development and clinical investigation of several photodynamic therapy agents, including four organic tetrapyrrolic derivatives (Photofrin, Chlorin e6, Visudyne and Foscan), and four metal‐based photosensitizers: WST11 (Pd II, , approved for vascular‐targeted of prostate cancer), Lutex (Lu III , lutetium texaphyrin, for cervical intraepithelial neoplasia), Purlytin (Sn IV , age‐related macular degeneration), and TLD1433 (Ru II , non‐muscle invasive bladder cancer) …”

Section: Introductionmentioning

confidence: 99%

“…[4] This potential of photoactivatable therapeutics, combined with the development of laser-and LED-based technologies for effective delivery of light to different tissues, has led to the development and clinical investigation of several photodynamic therapy agents, including four organic tetrapyrrolic derivatives (Photofrin, Chlorin e6, Visudyne and Foscan), and four metal-based photosensitizers: WST11 (Pd II, , approved for vascular-targeted of prostate cancer), [5] Lutex (Lu III , lutetium texaphyrin, for cervical intraepithelial neoplasia), Purlytin (Sn IV , age-related macular degeneration), and TLD1433 (Ru II , non-muscle invasive bladder cancer). [5,6,8] Although the application of metal-based complexes for phototherapy is at a relatively early stage compared to organic photosensitizers, the chemical know-how accumulat-ed over years of experience with cisplatin and other metal-based drugs can accelerate development of photoactivatable complexes. In turn, progress in this area provides new scope for the application of bioinorganic chemistry in medicine.…”

Section: Introductionmentioning

confidence: 99%

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New Designs for Phototherapeutic Transition Metal Complexes

et al. 2019

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In this Minireview, we highlight recent advances in the design of transition metal complexes for photodynamic therapy (PDT) and photoactivated chemotherapy (PACT), and discuss the challenges and opportunities for the translation of such agents into clinical use. New designs for light‐activated transition metal complexes offer photoactivatable prodrugs with novel targeted mechanisms of action. Light irradiation can provide spatial and temporal control of drug activation, increasing selectivity and reducing side‐effects. The photophysical and photochemical properties of transition metal complexes can be controlled by the appropriate choice of the metal, its oxidation state, the number and types of ligands, and the coordination geometry.

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Section: Pdt Agentsmentioning

confidence: 99%

Section: Pdt Agentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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New Designs for Phototherapeutic Transition Metal Complexes

et al. 2019

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“…Upon irradiation with blue light, these two complexes decreased the survival of P. aeruginosa down to 2 ± 1% (methyl substituted) and 6 ± 2% (glycoside substituted) while the biotin conjugate showed no significant decrease in bacterial survival [98]. Some cyclometallated Ir(III) complexes are known to act as photosensitizers, generating ROS upon light irradiation, making them potential candidates for aPDT as well [99]. This work seems to indicate that biotin conjugation may be another possibility to improve bacterial uptake of metal complexes to further improve their activity.…”

Section: Iridiummentioning

confidence: 99%

Metal Complexes, an Untapped Source of Antibiotic Potential?

2020

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With the widespread rise of antimicrobial resistance, most traditional sources for new drug compounds have been explored intensively for new classes of antibiotics. Meanwhile, metal complexes have long had only a niche presence in the medicinal chemistry landscape, despite some compounds, such as the anticancer drug cisplatin, having had a profound impact and still being used extensively in cancer treatments today. Indeed, metal complexes have been largely ignored for antibiotic development. This is surprising as metal compounds have access to unique modes of action and exist in a wider range of three-dimensional geometries than purely organic compounds. These properties make them interesting starting points for the development of new drugs. In this perspective article, the encouraging work that has been done on antimicrobial metal complexes, mainly over the last decade, is highlighted. Promising metal complexes, their activity profiles, and possible modes of action are discussed and issues that remain to be addressed are emphasized.Antibiotics 2020, 9, 90 2 of 24 Metal-containing compounds have played a small but seminal role in medicinal chemistry of throughout the 20th century. An arsenic-containing compound, Salvarsan, was discovered at the beginning of the century and became the first effective treatment of syphilis [9]. It was however the discovery of the anticancer drug cisplatin and its successors that really kickstarted the field of inorganic medicinal chemistry. Even today, platinum-based chemotherapeutics are still used in the majority of cancer treatments [10]. The gold-containing auranofin is an approved drug for the treatment of rheumatoid arthritis and is currently under investigation for its anticancer as well as antimicrobial properties [11][12][13][14][15][16]. Invigorated by these breakthrough successes, the field has expanded to many other elements in the last few decades, with complexes of titanium, iron, ruthenium, gallium, palladium, silver, gold, bismuth, and copper entering clinical trials [17][18][19][20][21][22]. The medicinal applications of these metal complexes range from anticancer to antimalaria over to neurodegenerative diseases. Strangely, antibacterial applications are remarkably sparse in this list and the number of literature reports on metal-based antimicrobials is dwarfed by the much more frequent publications on metal-based anticancer compounds. This is surprising as metals such as bismuth and silver have long been known to possess antibacterial properties. Some medicinal products are currently available. There are however a variety of products, such as silver-coated underwear, with a more dubious scientific basis. Nevertheless, the systematic evaluation of the antimicrobial properties of metal complexes has increased in pace over the last decade, with several reports highlighting the activity and potential modes of action of metal-based antibiotics. This perspective article will discuss the major discoveries in the non-traditional field of metal complex-based antibiotic co...

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Photosensitizers for Photodynamic Therapy

Lan

Zhao

Liu

et al. 2019

Adv Healthcare Materials

783

479

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As an emerging clinical modality for cancer treatment, photodynamic therapy (PDT) takes advantage of the cytotoxic activity of reactive oxygen species (ROS) that are generated by light irradiating photosensitizers (PSs) in the presence of oxygen (O2). However, further advancements including tumor selectivity and ROS generation efficiency are still required. Substantial efforts are devoted to design and synthesize smart PSs with optimized properties for achieving a desirable therapeutic efficacy. This review summarizes the recent progress in developing intelligent PSs for efficient PDT, ranging from single molecules to delicate nanomaterials. The strategies to improve ROS generation through optimizing photoinduced electron transfer and energy transfer processes of PSs are highlighted. Moreover, the approaches that combine PDT with other therapeutics (e.g., chemotherapy, photothermal therapy, and radiotherapy) and the targeted delivery in cancer cells or tumor tissue are introduced. The main challenges for the clinical application of PSs are also discussed.

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Recent Advances in the Design of Targeted Iridium(III) Photosensitizers for Photodynamic Therapy

Cited by 170 publications

References 73 publications

New Designs for Phototherapeutic Transition Metal Complexes

New Designs for Phototherapeutic Transition Metal Complexes

Metal Complexes, an Untapped Source of Antibiotic Potential?

Photosensitizers for Photodynamic Therapy

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