Asparaginase-Phage P22 Nanoreactors: Toward a Biobetter Development for Acute Lymphoblastic Leukemia Treatment
Por:
Diaz-Barriga, Cristina, Villanueva-Flores, Francisca, Quester, Katrin, Zarate-Romero, Andres, Cadena-Nava, Ruben Dario, Huerta-Saquero, Alejandro
Publicada:
1 may 2021
Categoría:
Pharmaceutical science
Resumen:
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 x 10(5) M-1 s(-1). ASNase-P22 showed an
aggregation of 60% of the volume sample when incubated at 37 degrees 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 degrees 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.
Filiaciones:
Diaz-Barriga, Cristina:
Centro de Nanociencias y Nanotecnología, Universidad Nacional Autónoma de México, Km. 107 Carretera Tijuana-Ensenada, Ensenada, 22860, Mexico
Villanueva-Flores, Francisca:
Centro de Nanociencias y Nanotecnología, Universidad Nacional Autónoma de México, Km. 107 Carretera Tijuana-Ensenada, Ensenada, 22860, Mexico
Quester, Katrin:
Centro de Nanociencias y Nanotecnología, Universidad Nacional Autónoma de México, Km. 107 Carretera Tijuana-Ensenada, Ensenada, 22860, Mexico
Zarate-Romero, Andres:
Centro de Nanociencias y Nanotecnología, Universidad Nacional Autónoma de México, Km. 107 Carretera Tijuana-Ensenada, Ensenada, 22860, Mexico
Cadena-Nava, Ruben Dario:
Centro de Nanociencias y Nanotecnología, Universidad Nacional Autónoma de México, Km. 107 Carretera Tijuana-Ensenada, Ensenada, 22860, Mexico
Huerta-Saquero, Alejandro:
Centro de Nanociencias y Nanotecnología, Universidad Nacional Autónoma de México, Km. 107 Carretera Tijuana-Ensenada, Ensenada, 22860, Mexico
Gold, Green Published, All Open Access; Gold
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