Dual-Agent Photodynamic Therapy with Optical Clearing Eradicates Pigmented Melanoma in Preclinical Tumor Models

Pires, Layla; Demidov, Valentin; Wilson, Brian C.; Sálvio, Ana Gabriela; Moriyama, Lílian Tan; Bagnato, Vanderlei Salvador; Vitkin, I. Alex; Kurachi, Cristina

doi:10.3390/cancers12071956

Cited by 29 publications

(16 citation statements)

References 53 publications

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“…The preclinical in vivo experiments described here support the hypothesis that the use of combined cellular and vascular PDT improves therapeutic response compared to single-agent PDT and that optical clearance results in improved tumor response to both single-and dual-agent PDT. The results also indicate the potential of PDT therapy with OCA enhancement in the treatment of pigmented lesions, including melanoma [43].…”

Section: Photothermal Therapymentioning

confidence: 62%

“…Treatment with lightactivated photosensitizers (photodynamic therapy, PDT) has shown limited tumor killing efficacy in pigmented melanoma, mainly due to light scattering and poor light penetration in this tissue [42]. To increase the treatment efficiency by reducing light scattering, an optical clearing agent (OCA) was applied to a mouse model of cutaneous melanoma shortly before the application of single and dual photosensitizer PDT [43].…”

Section: Photothermal Therapymentioning

confidence: 99%

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Treatment of malignant melanoma - a review of the literature

Kluz

Klas

2021

J Educ Health Sport

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Melanoma is caused by genetic mutations in melanocytes, pigment-producing cells found in the skin, eye, inner ear, and soft meninges. Sun exposure, atypical nevi, previous history of melanoma, and the presence of multiple (≥40) common nevi were found to be associated with an increased risk of melanoma detection (OR: 1. 3; 95% CI: 1. 1-1. 6). Its prevalence is highest among light-skinned populations and in regions of lower latitudes. Significance of family history of melanoma and presence of congenital nevi were excluded. For localized primary melanoma, the dominant prognostic factors for survival are lesion thickness, ulceration, and lymph node involvement Understanding the pathogenesis of melanoma has been crucial in developing new therapeutic approaches. The characterization of oncogenic signaling pathways and interactions has made it possible to identify new targets for clinically effective therapies, such as pathway inhibitors and antibodies to immune checkpoints or the use of phototherapy. In this article we describe the main signaling pathways which are deregulated in melanoma. We also mention how it has become a viable and crucial strategy for melanoma therapy and then thoroughly review the safety, clinical efficacy and progress regarding PDT- promising alternative therapy and the immunotherapies of melanoma in especially advanced metastatic stage basing on published clinical data and registered clinical trials, most of which are in phase III.

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Section: Photothermal Therapymentioning

confidence: 62%

Section: Photothermal Therapymentioning

confidence: 99%

Treatment of malignant melanoma - a review of the literature

Kluz

Klas

2021

J Educ Health Sport

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“…The cell growth inhibition was observed due to the irradiation on the cells without PIC treatment (green stars in Figure 5A). As a prospect of this approach in an in vivo study, the doses of irradiation can be increased to maximum energy fluence of 100 J/cm 2 , depending on the selected wavelength, however, visible light irradiation is unlikely to be toxic [42]. Optical microscopic observations before and after PIT demonstrated the bleb formation as signs of necrotic cell death.…”

Section: Photo-cytotoxicity Assaymentioning

confidence: 99%

“…Considering the fundamental restriction of light penetration, we suggest optimizing the excitation of PSs in deep tissue that may give us a highly flexible theranostic platform for HIV researches. This inevitably issue dictates the use of high-power irradiation [42]. The other alternatives for light delivery to the PICs in deep tissue could be the application of cellular-scale inorganic light-emitting diode (µ-ILED) arrays [43], or upconversion nanoparticles (UCNPs) in the field of PIT [44].…”

Section: Confocal Microscopy Studymentioning

confidence: 99%

Photoimmunotherapy Using Cationic and Anionic Photosensitizer-Antibody Conjugates against HIV Env-Expressing Cells

Sadraeian

Bahou

Cruz

et al. 2020

IJMS

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Different therapeutic strategies have been investigated to target and eliminate HIV-1-infected cells by using armed antibodies specific to viral proteins, with varying degrees of success. Herein, we propose a new strategy by combining photodynamic therapy (PDT) with HIV Env-targeted immunotherapy, and refer to it as HIV photoimmunotherapy (PIT). A human anti-gp41 antibody (7B2) was conjugated to two photosensitizers (PSs) with different charges through different linking strategies; “Click” conjugation by using an azide-bearing porphyrin attached via a disulfide bridge linker with a drug-to-antibody ratio (DAR) of exactly 4, and “Lysine” conjugation by using phthalocyanine IRDye 700DX dye with average DARs of 2.1, 3.0 and 4.4. These photo-immunoconjugates (PICs) were compared via biochemical and immunological characterizations regarding the dosimetry, solubility, and cell targeting. Photo-induced cytotoxicity of the PICs were compared using assays for apoptosis, reactive oxygen species (ROS), photo-cytotoxicity, and confocal microscopy. Targeted phototoxicity seems to be primarily dependent on the binding of PS-antibody to the HIV antigen on the cell membrane, whilst being independent of the PS type. This is the first report of the application of PIT for HIV immunotherapy by killing HIV Env-expressing cells.

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“…4,[20][21][22][23] In addition, it also has been reported that in vivo skin and skull optical clearing methods can effectively enhance the efficacy of photodynamic therapy. 24,25 Therefore, they have great potentials in clinical application.…”

Section: Introductionmentioning

confidence: 99%

Assessment of tissue‐specific changes in structure and function induced by in vivo skin/skull optical clearing techniques

Zhang

Feng

2021

Lasers Surg Med

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Background Objectives: Newly developed in vivo skin and skull optical clearing techniques can greatly improve the optical imaging performance, showing great advantages and clinical prospects. However, there is a poor understanding of in vivo optical clearing-induced changes in the skin and skull. Materials and Methods: Here, we employed in vivo skin/skull optical clearing techniques to improve the optical coherence tomography (OCT) imaging quality. And we also used polarization-sensitive OCT to monitor the dynamic changes in the polarization characteristics of the skin and skull during in vivo optical clearing processes. Two-photon imaging was used to evaluate changes in tissue barrier function and structure. Additionally, Raman spectra were employed for assessing the changes of each component in the skin and skull before and after optical clearing treatment. Results: The results indicated that the polarization states of the skin and skull were altered with the usages of optical clearing agents. And the barrier permeability and collagen fiber distribution of them became disordered. Furthermore, the Raman spectra of tissue demonstrated that the applications of in vivo tissue optical clearing methods could lead to the reduction of proteins, lipids, and inorganic salts in these two organs. Interestingly, after recovery treatment, the structure and function of the skin and skull could almost recover to the initial states. Conclusion:In vivo tissue optical clearing can lead to changes in the structure and function of tissue, which was reversible to some extent. This study plays an important role in revealing the underlying mechanisms of tissue optical clearing techniques; moreover, it is conducive to the development and optimization of a novel in vivo tissue optical clearing approaches in future.

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Dual-Agent Photodynamic Therapy with Optical Clearing Eradicates Pigmented Melanoma in Preclinical Tumor Models

Cited by 29 publications

References 53 publications

Treatment of malignant melanoma - a review of the literature

Treatment of malignant melanoma - a review of the literature

Photoimmunotherapy Using Cationic and Anionic Photosensitizer-Antibody Conjugates against HIV Env-Expressing Cells

Assessment of tissue‐specific changes in structure and function induced by in vivo skin/skull optical clearing techniques

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