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Article

Asparaginase-Phage P22 Nanoreactors: Toward a Biobetter Development for Acute Lymphoblastic Leukemia Treatment

Centro de Nanociencias y Nanotecnología, Universidad Nacional Autónoma de México, Km. 107 Carretera Tijuana-Ensenada, Ensenada 22860, Mexico
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Academic Editor: Avi Domb
Pharmaceutics 2021, 13(5), 604; https://doi.org/10.3390/pharmaceutics13050604
Received: 13 February 2021 / Revised: 28 February 2021 / Accepted: 2 March 2021 / Published: 22 April 2021
(This article belongs to the Special Issue Nanomaterials for Smart Therapeutic Treatments)
Asparaginase (ASNase) is a biopharmaceutical for Acute Lymphoblastic Leukemia (ALL) treatment. However, it shows undesirable side effects such as short lifetimes, susceptibility to proteases, and immunogenicity. Here, ASNase encapsidation was genetically directed in bacteriophage P22-based virus-like particles (VLPs) (ASNase-P22 nanoreactors) as a strategy to overcome these challenges. ASNase-P22 was composed of 58.4 ± 7.9% of coat protein and 41.6 ± 8.1% of tetrameric ASNase. Km and Kcat values of ASNase-P22 were 15- and 2-fold higher than those obtained for the free enzyme, respectively. Resulting Kcat/Km value was 2.19 × 105 M−1 s−1. ASNase-P22 showed an aggregation of 60% of the volume sample when incubated at 37 °C for 12 days. In comparison, commercial asparaginase was completely aggregated under the same conditions. ASNase-P22 was stable for up to 24 h at 37 °C, independent of the presence of human blood serum (HBS) or whether ASNase-P22 nanoreactors were uncoated or PEGylated. Finally, we found that ASNase-P22 caused cytotoxicity in the leukemic cell line MOLT-4 in a concentration dependent manner. To our knowledge, this is the first work where ASNase is encapsulated inside of VLPs, as a promising alternative to fight ALL. View Full-Text
Keywords: asparaginase nanoreactors; ALL treatment; P22 virus-like particles asparaginase nanoreactors; ALL treatment; P22 virus-like particles
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MDPI and ACS Style

Díaz-Barriga, C.; Villanueva-Flores, F.; Quester, K.; Zárate-Romero, A.; Cadena-Nava, R.D.; Huerta-Saquero, A. Asparaginase-Phage P22 Nanoreactors: Toward a Biobetter Development for Acute Lymphoblastic Leukemia Treatment. Pharmaceutics 2021, 13, 604. https://doi.org/10.3390/pharmaceutics13050604

AMA Style

Díaz-Barriga C, Villanueva-Flores F, Quester K, Zárate-Romero A, Cadena-Nava RD, Huerta-Saquero A. Asparaginase-Phage P22 Nanoreactors: Toward a Biobetter Development for Acute Lymphoblastic Leukemia Treatment. Pharmaceutics. 2021; 13(5):604. https://doi.org/10.3390/pharmaceutics13050604

Chicago/Turabian Style

Díaz-Barriga, Cristina, Francisca Villanueva-Flores, Katrin Quester, Andrés Zárate-Romero, Ruben D. Cadena-Nava, and Alejandro Huerta-Saquero. 2021. "Asparaginase-Phage P22 Nanoreactors: Toward a Biobetter Development for Acute Lymphoblastic Leukemia Treatment" Pharmaceutics 13, no. 5: 604. https://doi.org/10.3390/pharmaceutics13050604

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