Molecular Theranostic Agents for Photodynamic Therapy (PDT) and Magnetic Resonance Imaging (MRI)

Jenni, Sébastien; Sour, Angélique

doi:10.3390/inorganics7010010

Cited by 25 publications

(23 citation statements)

References 54 publications

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“…Further imaging techniques make use of specific paramagnetic or radiolabeled metalloporphyrins as contrast agents for magnetic resonance imaging (MRI) [ 35 , 36 ], and positron emission tomography (PET) [ 37 , 38 ] or near-infrared (NIR)-absorbing porphyrins for photoacoustic imaging (PAI) [ 39 , 40 ] of tissue. Concomitant with the development of multimodal drugs, more recently, porphyrins are investigated as potential theranostics combining therapeutic and diagnostic functions [ 19 , 41 , 42 ]. Finally, the application of porphyrinic compounds in drug delivery should be mentioned in connection with the design of smart, stimuli-responsive platforms for controlled drug release.…”

Section: Introductionmentioning

confidence: 99%

Probing the Interactions of Porphyrins with Macromolecules Using NMR Spectroscopy Techniques

2021

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Porphyrinic compounds are widespread in nature and play key roles in biological processes such as oxygen transport in blood, enzymatic redox reactions or photosynthesis. In addition, both naturally derived as well as synthetic porphyrinic compounds are extensively explored for biomedical and technical applications such as photodynamic therapy (PDT) or photovoltaic systems, respectively. Their unique electronic structures and photophysical properties make this class of compounds so interesting for the multiple functions encountered. It is therefore not surprising that optical methods are typically the prevalent analytical tool applied in characterization and processes involving porphyrinic compounds. However, a wealth of complementary information can be obtained from NMR spectroscopic techniques. Based on the advantage of providing structural and dynamic information with atomic resolution simultaneously, NMR spectroscopy is a powerful method for studying molecular interactions between porphyrinic compounds and macromolecules. Such interactions are of special interest in medical applications of porphyrinic photosensitizers that are mostly combined with macromolecular carrier systems. The macromolecular surrounding typically stabilizes the encapsulated drug and may also modify its physical properties. Moreover, the interaction with macromolecular physiological components needs to be explored to understand and control mechanisms of action and therapeutic efficacy. This review focuses on such non-covalent interactions of porphyrinic drugs with synthetic polymers as well as with biomolecules such as phospholipids or proteins. A brief introduction into various NMR spectroscopic techniques is given including chemical shift perturbation methods, NOE enhancement spectroscopy, relaxation time measurements and diffusion-ordered spectroscopy. How these NMR tools are used to address porphyrin–macromolecule interactions with respect to their function in biomedical applications is the central point of the current review.

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Section: Introductionmentioning

confidence: 99%

Probing the Interactions of Porphyrins with Macromolecules Using NMR Spectroscopy Techniques

2021

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“…With the advancement in medicine, drug designing has revolutionized from the utilization of different drugs for therapy and diagnostics separately to theranostics by integration of therapeutic and diagnostics potential into a single drug molecule 31 . In 1998, Funkhouser coined the term “Theranostic” defining those materials that combine both therapeutic approach and diagnostic imaging in a single entity, so that both the agents are delivered at the same time will show the same biodistribution pattern 31 , 32 . The theranostic field has the advantage of tuning the therapy and dose by gaining the ability to image and monitor the diseased tissue, delivery kinetics, and drug efficacy.…”

Section: Theranostics: ''Multifunctional Agents'' For Image-guided Photodynamic Therapymentioning

confidence: 99%

“…Further, studies have shown that PDT-induced changes alter proton behaviors in the tumor tissue and such changes can be enhanced using MRI contrast agents. Thus, MRI-guided PDT allows the determination of treatment parameters like PS concentration, light dose in relation to the final treatment outcome 32 .…”

Section: Theranostics: ''Multifunctional Agents'' For Image-guided Photodynamic Therapymentioning

confidence: 99%

“…Administration of Gd-based MRI contrast agents post-PS injection and PDT have already been shown to provide various sensitive information for the assessment of treatment outcome along with direct visualization of vascular damage for in vivo MRI-guided PDT in humans 21 , 32 . Although administration of contrast agent and PS as separate entities imparts the limitation of different pharmacodynamics and pharmacokinetics of two agents, resulting in differences in their biodistribution-based imaging.…”

Section: Theranostics: ''Multifunctional Agents'' For Image-guided Photodynamic Therapymentioning

confidence: 99%

“…Investigated agents were based on a chlorophyll-a derivative HPPH, conjugated with one, two, three, or six GdDTPA. HPPH-3GdDTPA was reported to be the best candidate with respect to its imaging and PDT efficacy 32 . Similarly, phthalocyanine and porphyrazine - Gd(III) contrast agent conjugates also showed promising results for cancer imaging with both MRI and NIR fluorescence, along with effective phototoxicity 147 , 148 .…”

Section: Theranostics: ''Multifunctional Agents'' For Image-guided Photodynamic Therapymentioning

confidence: 99%

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Recent Advances in Photosensitizers as Multifunctional Theranostic Agents for Imaging-Guided Photodynamic Therapy of Cancer

2021

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In recent years tremendous effort has been invested in the field of cancer diagnosis and treatment with an overall goal of improving cancer management, therapeutic outcome, patient survival, and quality of life. Photodynamic Therapy (PDT), which works on the principle of light-induced activation of photosensitizers (PS) leading to Reactive Oxygen Species (ROS) mediated cancer cell killing has received increased attention as a promising alternative to overcome several limitations of conventional cancer therapies. Compared to conventional therapies, PDT offers the advantages of selectivity, minimal invasiveness, localized treatment, and spatio-temporal control which minimizes the overall therapeutic side effects and can be repeated as needed without interfering with other treatments and inducing treatment resistance. Overall PDT efficacy requires proper planning of various parameters like localization and concentration of PS at the tumor site, light dose, oxygen concentration and heterogeneity of the tumor microenvironment, which can be achieved with advanced imaging techniques. Consequently, there has been tremendous interest in the rationale design of PS formulations to exploit their theranostic potential to unleash the imperative contribution of medical imaging in the context of successful PDT outcomes. Further, recent advances in PS formulations as activatable phototheranostic agents have shown promising potential for finely controlled imaging-guided PDT due to their propensity to specifically turning on diagnostic signals simultaneously with photodynamic effects in response to the tumor-specific stimuli. In this review, we have summarized the recent progress in the development of PS-based multifunctional theranostic agents for biomedical applications in multimodal imaging combined with PDT. We also present the role of different imaging modalities; magnetic resonance, optical, nuclear, acoustic, and photoacoustic in improving the pre-and post-PDT effects. We anticipate that the information presented in this review will encourage future development and design of PSs for improved image-guided PDT for cancer treatment.

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Gadolinium(III) Porphyrinoid Phototheranostics

Jin

Lai²,

Yang

et al. 2022

Chemistry An Asian Journal

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Molecular phototheranostics as an emerging field of modern precision medicine has recently attracted increasing research attention owing to non‐invasiveness, high precision, and controllable nature of light. In this work, we reported promising gadolinium (Gd3+) porphyrinoids as phototheranostic agents for magnetic resonance imaging (MRI) and photodynamic therapy (PDT). The synthesized Gd‐1‐4‐Glu featured with meso‐glycosylation and β‐lactonization to endow good biocompatibility and improved photophysical properties. In particular, β‐lactonization of glycosylated Gd3+ porphyrinoids substantially red‐shifted Q band absorption to near‐infrared (NIR) region and boosted generation of reactive oxygen species including 1O2, and some radical species that engaged in both type II and type I PDT pathways. In addition, the number and regioisomerism of β‐oxazolone moieties was observed to play an essential role in improving longitude relaxivity (r1) of Gd‐1‐4‐Glu of up to 4.3±0.2 mM−1s−1 by affecting environmental water exchange. Taking Gd‐4‐Glu as a promising complex, we further achieved real‐time T1‐weighted MRI and PDT on HeLa tumour mice in vivo, revealing the appealing potential of Gd3+ porphyrinoids in phototheranostics.

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Molecular Theranostic Agents for Photodynamic Therapy (PDT) and Magnetic Resonance Imaging (MRI)

Cited by 25 publications

References 54 publications

Probing the Interactions of Porphyrins with Macromolecules Using NMR Spectroscopy Techniques

Probing the Interactions of Porphyrins with Macromolecules Using NMR Spectroscopy Techniques

Recent Advances in Photosensitizers as Multifunctional Theranostic Agents for Imaging-Guided Photodynamic Therapy of Cancer

Gadolinium(III) Porphyrinoid Phototheranostics

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