Optical and nuclear imaging of glioblastoma with phosphatidylserine-targeted nanovesicles

Blanco, Víctor; Chu, Zhengtao; LaSance, Kathleen; Gray, Brian; Pak, Koon Y.; Rider, Therese; Greis, Kenneth D.; Qi, Xiaoyang

doi:10.18632/oncotarget.8763

Cited by 18 publications

(19 citation statements)

References 67 publications

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“…In another study, mice bearing intracranial U87ΔEGFR-Luc and X12v2 glioma received intravenous injection of SapC-DOPS, resulting in full tumor disappearance 250–350 days following drug injection among 25–75% of treated mice (Wojton et al, 2013 ). Interestingly, SapC-DOPS could also be conjugated with Gd (Winter et al, 2015 ), or with iodine-127 or iodine-124-fluorescent markers (Blanco et al, 2016 ), to image GBM tumors.…”

Section: The Different Gbm Treatments Commercialized or Under Developmentioning

confidence: 99%

Glioblastoma Treatments: An Account of Recent Industrial Developments

Alphandéry

2018

Front. Pharmacol.

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The different drugs and medical devices, which are commercialized or under industrial development for glioblastoma treatment, are reviewed. Their different modes of action are analyzed with a distinction being made between the effects of radiation, the targeting of specific parts of glioma cells, and immunotherapy. Most of them are still at a too early stage of development to firmly conclude about their efficacy. Optune, which triggers antitumor activity by blocking the mitosis of glioma cells under the application of an alternating electric field, seems to be the only recently developed therapy with some efficacy reported on a large number of GBM patients. The need for early GBM diagnosis is emphasized since it could enable the treatment of GBM tumors of small sizes, possibly easier to eradicate than larger tumors. Ways to improve clinical protocols by strengthening preclinical studies using of a broader range of different animal and tumor models are also underlined. Issues related with efficient drug delivery and crossing of blood brain barrier are discussed. Finally societal and economic aspects are described with a presentation of the orphan drug status that can accelerate the development of GBM therapies, patents protecting various GBM treatments, the different actors tackling GBM disease, the cost of GBM treatments, GBM market figures, and a financial analysis of the different companies involved in the development of GBM therapies.

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Section: The Different Gbm Treatments Commercialized or Under Developmentioning

confidence: 99%

Glioblastoma Treatments: An Account of Recent Industrial Developments

Alphandéry

2018

Front. Pharmacol.

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“…Lin et al formed an optical/PET agent by surface attachment of chelator-based 64 Cu and a Cy5.5 dye to ferritin nanocages [43]. Similarly, Blanco et al [44] developed a SapC-DOPS nanoparticle functionalized with an organic dye and radiolabelled with 124/127 I. PET imaging was used to quantify targeting to glioblastoma in vivo, with the optical dye potentially acting as a surgical marker to ensure all cancerous tissue is removed during invasive brain surgery.…”

Section: (C) Pet or Spect With Opticalmentioning

confidence: 99%

Multimodal nanoparticle imaging agents: design and applications

Burke

Cawthorne

Archibald

2017

Phil. Trans. R. Soc. A.

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Molecular imaging, where the location of molecules or nanoscale constructs can be tracked in the body to report on disease or biochemical processes, is rapidly expanding to include combined modality or multimodal imaging. No single imaging technique can offer the optimum combination of properties (e.g. resolution, sensitivity, cost, availability). The rapid technological advances in hardware to scan patients, and software to process and fuse images, are pushing the boundaries of novel medical imaging approaches, and hand-in-hand with this is the requirement for advanced and specific multimodal imaging agents. These agents can be detected using a selection from radioisotope, magnetic resonance and optical imaging, among others. Nanoparticles offer great scope in this area as they lend themselves, via facile modification procedures, to act as multifunctional constructs. They have relevance as therapeutics and drug delivery agents that can be tracked by molecular imaging techniques with the particular development of applications in optically guided surgery and as radiosensitizers. There has been a huge amount of research work to produce nanoconstructs for imaging, and the parameters for successful clinical translation and validation of therapeutic applications are now becoming much better understood. It is an exciting time of progress for these agents as their potential is closer to being realized with translation into the clinic. The coming 5-10 years will be critical, as we will see if the predicted improvement in clinical outcomes becomes a reality. Some of the latest advances in combination modality agents are selected and the progression pathway to clinical trials analysed.This article is part of the themed issue 'Challenges for chemistry in molecular imaging'.

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“…The six phenolic compounds were incorporated into SapC-DOPS nanovesicles as previously described [ 15 , 27 ]. The fluorescent nanovesicles were then tested for association with human U87Δ epidermal growth factor receptor (EGFR)-Luc GBM cells; these cells express a truncated, constitutively active, mutant epidermal growth factor receptor (EGFRvIII, obtained from Dr. Webster Cavenee; Ludwig Cancer Institute, San Diego, CA, USA) by flow cytometry using a BD Fortessa ( Figure 3 ).…”

Section: Methodsmentioning

confidence: 99%

“…In addition, the tumor microenvironment is acidic [ 25 ], which enhances the binding of SapC-DOPS to the surface PS of cancer cells. SapC-DOPS specifically targets PS on the surface of tumor cells in this acidic milieu, leading to ceramide accumulation, caspase activation and eventual apoptosis [ 15 ], selectively killing GBM tumor cells, without apparent off-target toxicity to normal cells and tissues [ 26 , 27 , 28 ]. Indeed, SapC-DOPS has shown an exemplary safety profile in Phase I clinical trials [ 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

Biotherapy of Brain Tumors with Phosphatidylserine-Targeted Radioiodinated SapC-DOPS Nanovesicles

Davis

Vallabhapurapu

Chu

et al. 2020

Cells

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Glioblastoma multiforme (GBM), a common type of brain cancer, has a very poor prognosis. In general, viable GBM cells exhibit elevated phosphatidylserine (PS) on their membrane surface compared to healthy cells. We have developed a drug, saposin C-dioleoylphosphatidylserine (SapC-DOPS), that selectively targets cancer cells by honing in on this surface PS. To examine whether SapC-DOPS, a stable, blood–brain barrier-penetrable nanovesicle, could be an effective delivery system for precise targeted therapy of radiation, we iodinated several carbocyanine-based fluorescent reporters with either stable iodine (127I) or radioactive isotopes (125I and 131I). While all of the compounds, when incorporated into the SapC-DOPS delivery system, were taken up by human GBM cell lines, we chose the two that best accumulated in the cells (DiI (22,3) and DiD (16,16)). Pharmacokinetics were conducted with 125I-labeled compounds and indicated that DiI (22,3)-SapC-DOPS had a time to peak in the blood of 0.66 h and an elimination half-life of 8.4 h. These values were 4 h and 11.5 h, respectively, for DiD (16,16)-SapC-DOPS. Adult nude mice with GBM cells implanted in their brains were treated with 131I-DID (16,16)-SapC-DOPS. Mice receiving the radionuclide survived nearly 50% longer than the control groups. These data suggest a potential novel, personalized treatment for a devastating brain disease.

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Optical and nuclear imaging of glioblastoma with phosphatidylserine-targeted nanovesicles

Cited by 18 publications

References 67 publications

Glioblastoma Treatments: An Account of Recent Industrial Developments

Glioblastoma Treatments: An Account of Recent Industrial Developments

Multimodal nanoparticle imaging agents: design and applications

Biotherapy of Brain Tumors with Phosphatidylserine-Targeted Radioiodinated SapC-DOPS Nanovesicles

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