Chemiluminescence and Bioluminescence as an Excitation Source in the Photodynamic Therapy of Cancer: A Critical Review

Magalhães, Carla M.; Silva, Joaquim C. G. Esteves da; Silva, Luís Pinto da

doi:10.1002/cphc.201600270

Cited by 88 publications

(108 citation statements)

References 85 publications

(352 reference statements)

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“…One of the most important and popular chemiluminescent systems is the luminol molecule (5‐amino‐2,3‐dihydrophthalazine‐1,4‐dione, LH 2 ), which is widely used in forensic science to detect traces of blood, since it is catalyzed by iron of the hemoglobin protein . First discovered in 1928 by Albrecht, the chemiluminescence of LH 2 has since been the topic of many fundamental studies and the development of commercial analytical assay kits and challenging therapeutic procedures to treat cancers in deep tissues . It is worth mentioning in this last context, for example, investment from hospitals and research groups to find noninvasive methods to treat inaccessible tumors, for example, the glioblastoma multiforme brain tumor, by means of mitochondria‐targeting LH 2 systems .…”

Section: Introductionmentioning

confidence: 99%

Molecular Basis of the Chemiluminescence Mechanism of Luminol

Giussani

Farahani

Martínez‐Muñoz

et al. 2019

Chemistry A European J

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Light emission from luminol is probably one of the most popular chemiluminescence reactions due to its use in forensic science, and has recently displayed promising applications for the treatment of cancer in deep tissues. The mechanism is, however, very complex and distinct possibilities have been proposed. By efficiently combining DFT and CASPT2 methodologies, the chemiluminescence mechanism has been studied in three steps: 1) luminol oxygenation to generate the chemiluminophore, 2) a chemiexcitation step, and 3) generation of the light emitter. The findings demonstrate that the luminol double‐deprotonated dianion activates molecular oxygen, diazaquinone is not formed, and the chemiluminophore is formed through the concerted addition of oxygen and concerted elimination of nitrogen. The peroxide bond, in comparison to other isoelectronic chemical functionalities (−NH−NH−, −N−−N−−, and −S−S−), is found to have the best chemiexcitation efficiency, which allows the oxygenation requirement to be rationalized and establishes general design principles for the chemiluminescence efficiency. Electron transfer from the aniline ring to the OO bond promotes the excitation process to create an excited state that is not the chemiluminescent species. To produce the light emitter, proton transfer between the amino and carbonyl groups must occur; this requires highly localized vibrational energy during chemiexcitation.

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Section: Introductionmentioning

confidence: 99%

Molecular Basis of the Chemiluminescence Mechanism of Luminol

Giussani

Farahani

Martínez‐Muñoz

et al. 2019

Chemistry A European J

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“…The absence of photoexcitation also eliminates problems associated with light penetration into biologic tissue. Given this, chemiluminescent and bioluminescent systems have been used in the real‐time imaging of target molecules and processes, both in vivo and in vitro, and have been explored as excitation sources in photodynamic therapy of cancer …”

Section: Introductionmentioning

confidence: 99%

“…In most chemiluminescent and bioluminescent systems, light is generated via a similar two‐step mechanism: the oxidation of the substrate, with production of an unstable and energy‐rich cyclic peroxide intermediate (Scheme ); and the subsequent thermolysis of the peroxide intermediate, which allows for a thermally activated singlet ground state ( S 0 ) reaction to produce an oxidized reaction product in first singlet excited state ( S 1 ) (Scheme ) . Chemiexcitation can also lead to generation of products in their first triplet state ( T 1 ).…”

Section: Introductionmentioning

confidence: 99%

Mechanistic insights into the efficient intramolecular chemiexcitation of dioxetanones from TD‐DFT and multireference calculations

Silva

Magalhães

2018

Int J of Quantum Chemistry

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Despite decades of research, it is still not clear what is the mechanism behind the efficient chemiexcitation of dioxetanones in chemiluminescent and bioluminescent reactions. In fact, long‐standing theories (charge transfer‐initiated luminescence and chemically induced electron‐exchange luminescence) have been demonstrated to not be able to explain this phenomenon. Herein, a theoretical approach using reliable and up‐to‐date methodology was used to address this problem, by focusing on model dioxetanones. Time‐dependent (TD)‐Density functional theory (DFT) and multireference complete‐active‐space second‐order perturbation theory (CASPT2) calculations provided evidence that points to efficient intramolecular chemiexcitation being the result of the reacting molecules having access to a long zone of the Potential energy surface (PES), within the biradicalar region, where S0 and S1 are degenerate. Molecules with inefficient chemiexcitation are unable to reach this zone of degeneracy. Our main finding is that access to the region of degeneracy appears to be given due to increased interaction between the keto and CO2 moieties, as supported by the use of the activation strain model and Born‐Oppenheimer molecular dynamics, which extends the biradical region by delaying the rupture of the peroxide ring. Increased interaction derives from attractive electrostatic interactions between the moieties of dioxetanone. Thus, we hypothesize that efficient chemiexcitation results not only from electron/charge transfer and subsequent charge annihilation but is instead based on the degree of interaction between the keto and CO2 moieties, which controls the access to a region of degeneracy between the ground and excited states.

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“…2, 3 A recent advanced approach that attempted to overcome the limitation of tissue penetration of light is the use of chemi/bioluminescent systems that can avoid the external light and use chemi/bioluminescence is an internal light source. 4, 5 …”

Section: Introductionmentioning

confidence: 99%

Cerenkov Radiation Induced Photodynamic Therapy Using Chlorin e6-Loaded Hollow Mesoporous Silica Nanoparticles

Kamkaew¹,

Cheng

Goel³

et al. 2016

ACS Appl. Mater. Interfaces

146

113

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Traditional photodynamic therapy (PDT) requires external light to activate photosensitizers for therapeutic purposes. However, the limited tissue penetration of light is still a major challenge for this method. To overcome this limitation, we report an optimized system that uses Cerenkov radiation for PDT by using radionuclides to activate a well-known photosensitizer (Chlorin e6, Ce6). By taking advantage of hollow mesoporous silica nanoparticles (HMSNs) that can intrinsically radiolabel oxophilic zirconium-89 (89Zr, t1/2 = 78.4 h) radionuclide, as well as possess great drug loading capacity, Ce6 can be activated by Cerenkov radiation from 89Zr in the same nanoconstruct. In vitro cells viability experiments demonstrated dose-dependent cell deconstructions as a function of concentration of Ce6 and 89Zr. In vivo studies show inhibition of tumor growth when mice were subcutaneously injected with [89Zr]HMSN-Ce6 and histological analysis of tumor section showed damage to tumor tissues, implying that reactive oxygen species mediated the destruction. This study offers a way to use internal radiation source to achieve deep-seated tumor therapy without using any external light source for future applications.

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Chemiluminescence and Bioluminescence as an Excitation Source in the Photodynamic Therapy of Cancer: A Critical Review

Cited by 88 publications

References 85 publications

Molecular Basis of the Chemiluminescence Mechanism of Luminol

Molecular Basis of the Chemiluminescence Mechanism of Luminol

Mechanistic insights into the efficient intramolecular chemiexcitation of dioxetanones from TD‐DFT and multireference calculations

Cerenkov Radiation Induced Photodynamic Therapy Using Chlorin e6-Loaded Hollow Mesoporous Silica Nanoparticles

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