Targeted Myoglobin Delivery as a Strategy for Enhancing the Sensitivity of Hypoxic Cancer Cells to Radiation

Yang, Zaofeng; Heater, Bradley S.; Cuddington, Clayton; Palmer, Andre F.; Lee, Marianne M.M.; Chan, Michael K.

doi:10.1016/j.isci.2020.101158

Cited by 18 publications

(20 citation statements)

References 53 publications

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“…Collectively, Mb might assume positive roles in slowing cancer progression. Most recently, targeted delivery of O 2 -bound myoglobin was suggested to be an effective approach to enhance the efficacy of radiotherapy via increasing intracellular oxygen levels [ 201 ].…”

Section: Myoglobinmentioning

confidence: 99%

Lessons from the post-genomic era: Globin diversity beyond oxygen binding and transport

et al. 2020

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Vertebrate hemoglobin (Hb) and myoglobin (Mb) were among the first proteins whose structures and sequences were determined over 50 years ago. In the subsequent pregenomic period, numerous related proteins came to light in plants, invertebrates and bacteria, that shared the myoglobin fold, a signature sequence motif characteristic of a 3-on-3 α-helical sandwich. Concomitantly, eukaryote and bacterial globins with a truncated 2-on-2 α-helical fold were discovered. Genomic information over the last 20 years has dramatically expanded the list of known globins, demonstrating their existence in a limited number of archaeal genomes, a majority of bacterial genomes and an overwhelming majority of eukaryote genomes. In vertebrates, 6 additional globin types were identified, namely neuroglobin (Ngb), cytoglobin (Cygb), globin E (GbE), globin X (GbX), globin Y (GbY) and androglobin (Adgb). Furthermore, functions beyond the familiar oxygen transport and storage have been discovered within the vertebrate globin family, including NO metabolism, peroxidase activity, scavenging of free radicals, and signaling functions. The extension of the knowledge on globin functions suggests that the original roles of bacterial globins must have been enzymatic, involved in defense against NO toxicity, and perhaps also as sensors of O 2 , regulating taxis away or towards high O 2 concentrations. In this review, we aimed to discuss the evolution and remarkable functional diversity of vertebrate globins with particular focus on the variety of non-canonical expression sites of mammalian globins and their according impressive variability of atypical functions.

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Section: Myoglobinmentioning

confidence: 99%

Lessons from the post-genomic era: Globin diversity beyond oxygen binding and transport

et al. 2020

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“…Michael K. Chan’s group has provided the most comprehensive investigation to date on this aspect. They published [ 45 , 91 , 92 , 93 , 94 , 95 ] and patented [ 96 , 97 , 98 ] a strategy involving different Cry toxins and more specifically Cry3Aa, which they selected for further investigations for several reasons. Cry3Aa is a toxin with high self-assembly propensity that is able to crystallize both in vitro and in vivo with similar crystal packing interfaces, indicating that its crystallization process is strongly driven by the toxin itself, pending an adequate toxin concentration [ 31 , 99 , 100 ].…”

Section: Functionalizing Toxin Crystals For the Development Of New Biotechnological Toolsmentioning

confidence: 99%

“…The same group also explored the potential of Cry3Aa crystals for drug delivery [ 91 , 94 , 95 ]. The use of crystalline formulations for the storage and delivery of biopharmaceutical proteins has received increasing interest during the last decade [ 13 , 103 , 104 ] as it offers many advantages associated with their higher stability, long-lasting and progressive diffusion within the organism, and long-term storage [ 3 , 4 ].…”

Section: Functionalizing Toxin Crystals For the Development Of New Biotechnological Toolsmentioning

confidence: 99%

“…In vivo crystallization, notably using Bt , could allow an expansion of the set of crystalline biopharmaceuticals in the market. Cry3Aa was shown to successfully entrap antimicrobial peptides and myoglobin, which could be further taken up by macrophages and cancer cells, respectively [ 94 , 95 ]. Moreover, by using only the first domain of Cry3Aa, an important domain for Cry3Aa crystallization in Bt [ 31 , 107 ], for fusion with myoglobin, results comparable to those with fusions using the full toxin were obtained, indicating that only some parts of the toxin might be sufficient to stabilize the cargo protein.…”

Section: Functionalizing Toxin Crystals For the Development Of New Biotechnological Toolsmentioning

confidence: 99%

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Can (We Make) Bacillus thuringiensis Crystallize More Than Its Toxins?

Tetreau

Андреева

Banneville

et al. 2021

Toxins

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The development of finely tuned and reliable crystallization processes to obtain crystalline formulations of proteins has received growing interest from different scientific fields, including toxinology and structural biology, as well as from industry, notably for biotechnological and medical applications. As a natural crystal-making bacterium, Bacillus thuringiensis (Bt) has evolved through millions of years to produce hundreds of highly structurally diverse pesticidal proteins as micrometer-sized crystals. The long-term stability of Bt protein crystals in aqueous environments and their specific and controlled dissolution are characteristics that are particularly sought after. In this article, I explore whether the crystallization machinery of Bt can be hijacked as a means to produce (micro)crystalline formulations of proteins for three different applications: (i) to develop new bioinsecticidal formulations based on rationally improved crystalline toxins, (ii) to functionalize crystals with specific characteristics for biotechnological and medical applications, and (iii) to produce microcrystals of custom proteins for structural biology. By developing the needs of these different fields to figure out if and how Bt could meet each specific requirement, I discuss the already published and/or patented attempts and provide guidelines for future investigations in some underexplored yet promising domains.

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“…To obtain a high affinity and specific binder to GPC-3, the tumor-targeting peptide with the advantage of synthesis and modification is an alternative to other than traditional antibodies (11,12). Recently, phage-displayed libraries containing numerous randomized peptides on the surface of phages are becoming more popular for screening a specific binder to the selected target.…”

Section: Introductionmentioning

confidence: 99%

Identification of a Glypican-3 Binding Peptide From a Phage-Displayed Peptide Library for PET Imaging of Hepatocellular Carcinoma

Yan

Chen

et al. 2021

Front. Oncol.

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Tumor-targeting peptides functioned as molecular probes are essential for multi-modality imaging and molecular-targeting therapy in caner theronostics. Here, we performed a phage-displayed bio-panning to identify a specific binding peptide targeting Glypican-3 (GPC-3), a promising biomarker in hepatocellular carcinoma (HCC). After screening in the cyclic peptide library, a candidate peptide named F3, was isolated and showed specific binding to HCC cell lines. In a bio-distribution study, higher accumulation of F3 peptide was observed in HepG-2 tumors compared to PC-3 tumors in xenograft models. After labeling with radioactive 68Ga, the F3 peptide tracer enabled the specific detection of tumors in HCC tumor models with PET imaging. More importantly, the expression of GPC-3 in human tissue samples may be distinguished by an F3 fluorescent peptide probe indicating its potential for clinical application. This cyclic peptide targeting GPC-3 has been validated, and may be an alternative to serve as an imaging probe or a targeting domain in the drug conjugate.

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Targeted Myoglobin Delivery as a Strategy for Enhancing the Sensitivity of Hypoxic Cancer Cells to Radiation

Cited by 18 publications

References 53 publications

Lessons from the post-genomic era: Globin diversity beyond oxygen binding and transport

Lessons from the post-genomic era: Globin diversity beyond oxygen binding and transport

Can (We Make) Bacillus thuringiensis Crystallize More Than Its Toxins?

Identification of a Glypican-3 Binding Peptide From a Phage-Displayed Peptide Library for PET Imaging of Hepatocellular Carcinoma

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