Intraoperative Photodynamic Surgery (iPDS) with Acridine Orange for Musculoskeletal Sarcomas

Kusuzaki, Katsuyuki; Matsubara, Takehiro; Satonaka, Haruhiko; Matsumine, Akihiko; Nakamura, Tomoki; Sudo, Akihiro; Murata, Hiroaki; Hosogi, Shigekuni; Baldini, Nicola

doi:10.7759/cureus.204

Cited by 17 publications

(19 citation statements)

References 45 publications

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“…AO produces orange fluorescence when it binds to RNA and green fluorescence when it binds to DNA. However, this behavior differs significantly in live, apoptotic, and fixed permeabilized cells (6).…”

Section: Resultsmentioning

confidence: 99%

“…The novel research field of acridines is focused on their application in cancer theranostics due to its unique feature of preferential accumulation in the acidic environment of the tumor tissues and strong fluorescent properties (1, 6). AO has been recently explored in several preclinical (Figures 1A,B) and clinical studies for specific tumor cells targeting.…”

Section: Introductionmentioning

confidence: 99%

“…Tumors emit green fluorescence (arrows). Injection site of the tail vein also emits green fluorescence Figure adapted with permission from: Kusuzaki et al (6) (CC-BY 3.0).…”

Section: Introductionmentioning

confidence: 99%

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Acridine Orange: A Review of Novel Applications for Surgical Cancer Imaging and Therapy

et al. 2019

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Introduction: Acridine orange (AO) was first extracted from coal tar in the late nineteenth century and was used as a fluorescent dye. In this paper, we review emergent research about novel applications of AO for fluorescence surgery and cancer therapy.Materials and methods: We performed a systematic search in the MEDLINE, PubMed, Cochrane library, Google Scholar, Embase, Web of Science, and Scopus database using combinations of the term “acridine orange” with the following: “surgical oncology,” “neuropathology,” “microsurgery,” “intraoperative fluorescence,” “confocal microscopy,” “pathology,” “endomicroscopy,” “guidance,” “fluorescence guidance,” “oncology,” “surgery,” “neurooncology,” and “photodynamic therapy.” Peer-reviewed articles published in English were included in this review. We have also scanned references for relevant articles.Results: We have reviewed studies on the various application of AO in microscopy, endomicroscopy, intraoperative fluorescence guidance, photodynamic therapy, sonodynamic therapy, radiodynamic therapy.Conclusion: Although the number of studies on the clinical use of AO is limited, pilot studies have demonstrated the safety and feasibility of its application as an intraoperative fluorescent dye and as a novel photo- and radio-sensitizator. Further clinical studies are necessary to more definitively assess the clinical benefit AO-based fluorescence guidance, therapy for sarcomas, and to establish feasibility of this new approach for the treatment of other tumor types.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Acridine Orange: A Review of Novel Applications for Surgical Cancer Imaging and Therapy

et al. 2019

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“…In a third experiment, lysosomal abundance and activity (during starvation) were recorded by staining 18 animals from each age group (allowed to feed for 4, 10, 15, 25 Days Post-Metamorphosis DPM), with Acridine Orange, a fluorescent stain that aggregates in extremely acidic regions (pH < 4.5) [ 46 , 49 , 50 ] ( Table 2 ). As Acridine Orange stains acidic organelles in living tissues, living animals were first stained for 30 minutes at room temperature (diluted with filtered seawater to a 5μmol solution) and then vivisected, mounted and imaged on the same microscope using the blue laser (excitation 488nm), with 645-670nm (AO dimer type optimum: 656) as the accepted emission range [ 46 ].…”

Section: Methodsmentioning

confidence: 99%

Chloroplast digestion and the development of functional kleptoplasty in juvenile Elysia timida (Risso, 1818) as compared to short-term and non-chloroplast-retaining sacoglossan slugs

Laetz

Wägele

2017

PLoS ONE

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Sacoglossan sea slugs are the only metazoans known to perform functional kleptoplasty, the sequestration and retention of functional chloroplasts within their digestive gland cells. Remarkably, a few species with this ability can survive starvation periods of 3–12 months likely due to their stolen chloroplasts. There are no reports of kleptoplast transfer from mother slug to either eggs or juveniles, demonstrating that each animal must independently acquire its kleptoplasts and develop the ability to maintain them within its digestive gland. We present here an investigation into the development of functional kleptoplasty in a long-term kleptoplast retaining species, Elysia timida. Laboratory-reared juvenile slugs of different post-metamorphic ages were placed in starvation and compared to 5 known short-term retaining slug species and 5 non-retaining slug species. The subsequent results indicate that functional kleptoplasty is not performed by E. timida until after 15 days post-metamorphosis and that by 25 days, these animals outlive many of the short-term retention species. Digestive activity was also monitored using lysosomal abundance as an indicator, revealing different patterns in starving juveniles versus adults. Starved juveniles were reintroduced to food to determine any differences in digestive activity when starvation ends, resulting in an increase in the number of kleptoplasts, but no overall change in lysosomal activity. By revealing some of the changes that occur during early development in these animals, which begin as non-kleptoplast-retaining and grow into long-term retaining slugs, this investigation provides a basis for future inquiries into the origin and development of this remarkable ability.

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“…Acridine orange (AO), a weak basic dye, extracted from coal tar over 100 years ago, is an effective PS which has shown cytocidal effect on multidrug resistant osteosarcoma cells and tumor suppression in musculoskeletal sarcomas . AO fluoresces green when excited with blue light which allows for direct visualization of the tumors as an assisting aid during surgery …”

Section: Introductionmentioning

confidence: 99%

Molecular Entrapment in Thermophilic Ferritin for Nanoformulation in Photodynamic Therapy

Pasula

Kuniyil

Lim

2020

Advanced Therapeutics

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Nanoformulation of therapeutic and diagnostic agents is beneficial as they accumulate at tumor sites due to enhanced permeability and retention effects. However, many in vitro studies performed on 2D cultures lack the realistic dimension of in vivo systems. In this work, a photosensitizer, acridine orange (AO), used in photodynamic therapy of cancer, is nanoformulated by entrapment in thermophilic ferritin. The efficacy is tested on 2D and 3D in vitro models and complemented with studies on the cellular uptake routes. Ferritin from the archaeon Archaeoglobus fulgidus (AfFtn) exhibits the unique property of divalent metal ion or ionic strength mediated assembly, making it an interesting nanocarrier for the entrapment of small molecules. The photosensitization and toxicity studies on 2D monolayers and 3D spheroid models of colorectal cancer cells show that AO loaded in AfFtn is functional. The killing efficiency in 2D monolayers reaches 50% while the growth of 3D spheroids is arrested after the first day with a subsequent 10% reduction of tumor diameter over the next 2 days. Results show that AO loaded AfFtn has better penetration ability than free AO alone in 3D spheroid models indicating that nanocage formulation provides for an efficient delivery vehicle into the tumor tissue.

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Intraoperative Photodynamic Surgery (iPDS) with Acridine Orange for Musculoskeletal Sarcomas

Cited by 17 publications

References 45 publications

Acridine Orange: A Review of Novel Applications for Surgical Cancer Imaging and Therapy

Acridine Orange: A Review of Novel Applications for Surgical Cancer Imaging and Therapy

Chloroplast digestion and the development of functional kleptoplasty in juvenile Elysia timida (Risso, 1818) as compared to short-term and non-chloroplast-retaining sacoglossan slugs

Molecular Entrapment in Thermophilic Ferritin for Nanoformulation in Photodynamic Therapy

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