Polyoxazoline-Conjugated <scp>l</scp>-Asparaginase: An Antibody-Production-Free Therapeutic Agent for Acute Lymphoblastic Leukemia

Yamada, Taiga; Ishimaru, Marika; Shoji, Takuma; Tomiyasu, Hirotaka; Tochinai, Ryota; Taguchi, Kazuaki; Komatsu, Teruyuki

doi:10.1021/acsabm.3c00888

ACS Appl. Bio Mater.

2023

DOI: 10.1021/acsabm.3c00888

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Polyoxazoline-Conjugated l-Asparaginase: An Antibody-Production-Free Therapeutic Agent for Acute Lymphoblastic Leukemia

Taiga Yamada,

Marika Ishimaru,

Takuma Shoji

et al.

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2024

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Cited by 2 publications

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Synthesis and Physicochemical Properties of Poly(2‐Alkyl‐2‐Oxazoline)‐Conjugated Hemoglobins as an Artificial O₂ Carrier: Comparison with Polyethylene Glycol Conjugates

Wakabayashi,

Ishii,

Yamada

et al. 2024

Macro Chemistry & Physics

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Polyethylene glycol (PEG) is a biocompatible polymer extensively employed to prolong blood circulation and mitigate the immunogenicity of the protein therapeutics. Nonetheless, there are reports of anti‐PEG antibody production. Poly(2‐alkyl‐2‐oxazoline) (PROx) exhibits analogous immunological stealth properties and represents a potential substitute for PEG. This study details the synthesis of PROx‐conjugated hemoglobins (PROxm‐Hbs, R = Me, Et) as artificial O2 carriers, functioning as red blood cell (RBC) substitutes, and evaluates their O2 affinities and solution properties. The average number of polymers bound is designed to be 6 or 11. The O2 affinities (P50) of PMeOxm‐Hbs and PEtOxm‐Hbs are ascertained as 9 Torr, comparable to those of PEG‐conjugated Hbs (PEGm‐Hbs). The PEtOx6‐HbT, synthesized under an N2 atmosphere, exhibited a low O2 affinity (P50 = 57 Torr). Through the admixture of PEtOx6‐Hb and PEtOx6‐HbT, the P50 value of the formulation to range from 9 to 57 Tor can be tailored as desired. The colloid osmotic pressures and viscosities of PMeOxm‐Hb and PEtOxm‐Hb solutions are lower than those of the corresponding PEGm‐Hb solutions. Furthermore, the PROx conjugates evinced no cytotoxicity against normal cells. PMeOxm‐Hbs and PEtOxm‐Hbs, characterized by their appropriate O2 affinities and solution properties, present themselves as promising alternative materials to RBCs.

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Synthesis and Physicochemical Properties of Poly(2‐Alkyl‐2‐Oxazoline)‐Conjugated Hemoglobins as an Artificial O₂ Carrier: Comparison with Polyethylene Glycol Conjugates

Wakabayashi,

Ishii,

Yamada

et al. 2024

Macro Chemistry & Physics

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Asparagine: A key metabolic junction in targeted tumor therapy

Wang,

Gong,

Xiong

et al. 2024

Pharmacological Research

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Polyoxazoline-Conjugated l-Asparaginase: An Antibody-Production-Free Therapeutic Agent for Acute Lymphoblastic Leukemia

Cited by 2 publications

References 38 publications

Synthesis and Physicochemical Properties of Poly(2‐Alkyl‐2‐Oxazoline)‐Conjugated Hemoglobins as an Artificial O₂ Carrier: Comparison with Polyethylene Glycol Conjugates

Synthesis and Physicochemical Properties of Poly(2‐Alkyl‐2‐Oxazoline)‐Conjugated Hemoglobins as an Artificial O₂ Carrier: Comparison with Polyethylene Glycol Conjugates

Asparagine: A key metabolic junction in targeted tumor therapy

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Polyoxazoline-Conjugated l-Asparaginase: An Antibody-Production-Free Therapeutic Agent for Acute Lymphoblastic Leukemia

Cited by 2 publications

References 38 publications

Synthesis and Physicochemical Properties of Poly(2‐Alkyl‐2‐Oxazoline)‐Conjugated Hemoglobins as an Artificial O2 Carrier: Comparison with Polyethylene Glycol Conjugates

Synthesis and Physicochemical Properties of Poly(2‐Alkyl‐2‐Oxazoline)‐Conjugated Hemoglobins as an Artificial O2 Carrier: Comparison with Polyethylene Glycol Conjugates

Asparagine: A key metabolic junction in targeted tumor therapy

Contact Info

Product

Resources

About

Synthesis and Physicochemical Properties of Poly(2‐Alkyl‐2‐Oxazoline)‐Conjugated Hemoglobins as an Artificial O₂ Carrier: Comparison with Polyethylene Glycol Conjugates

Synthesis and Physicochemical Properties of Poly(2‐Alkyl‐2‐Oxazoline)‐Conjugated Hemoglobins as an Artificial O₂ Carrier: Comparison with Polyethylene Glycol Conjugates