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<p>Protein therapeutics have gained market share in the medical community worldwide. However, proteins cannot cross cell membranes, and they can be degraded in the intracellular or extracellular environment. Materials that are used in pharmaceutical formulations play crucial roles in allowing the proteins they deliver to perform the appropriate functions. The copolymer of 2-methacryloyloxyethyl phosphorylcholine (MPC) and <i>n</i>-butyl methacrylate (BMA) is a phospholipid-mimicking polymer that has excellent biocompatibility and direct cell-penetrating properties. In this study, the phospholipid polymer-based bioconjugation polymer poly[MPC-<i>co</i>-BMA-<i>co</i>-<i>N</i>-succinimidyloxycarbonyl tetra(ethylene glycol) methacrylate (MENHS)] (PMBS) was synthesized and conjugated with OVA: ovalbumin (as a model protein). We investigated the effect of the PMBS and OVA mixing ratio on the cellular internalization of OVA to evaluate the ability of this formulation to control immune responses in a murine dendritic cell line. The bioconjugate of PMBS-OVA formed polymolecular associations in aqueous solution. The PMBS-OVA conjugate that contained a greater amount of PMBS delivered OVA into the cytosol at 4 °C, which is a condition that inhibits the endocytic pathway. Although the PMBS-OVA conjugate did not affect cytokine production, it increased antigen presentation via major histocompatibility complex class I. Therefore, we successfully prepared a bioconjugate that exhibits excellent biocompatibility and cans directly deliver a protein into the cytosol using phospholipid polymers.</p>

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Direct cytosolic delivery of antigenic proteins via phospholipid polymer bioconjugates

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月31日

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  • Yuta Yoshizaki,
  • Koki Onoda,
  • Tomohiro Konno

摘要

Protein therapeutics have gained market share in the medical community worldwide. However, proteins cannot cross cell membranes, and they can be degraded in the intracellular or extracellular environment. Materials that are used in pharmaceutical formulations play crucial roles in allowing the proteins they deliver to perform the appropriate functions. The copolymer of 2-methacryloyloxyethyl phosphorylcholine (MPC) and n-butyl methacrylate (BMA) is a phospholipid-mimicking polymer that has excellent biocompatibility and direct cell-penetrating properties. In this study, the phospholipid polymer-based bioconjugation polymer poly[MPC-co-BMA-co-N-succinimidyloxycarbonyl tetra(ethylene glycol) methacrylate (MENHS)] (PMBS) was synthesized and conjugated with OVA: ovalbumin (as a model protein). We investigated the effect of the PMBS and OVA mixing ratio on the cellular internalization of OVA to evaluate the ability of this formulation to control immune responses in a murine dendritic cell line. The bioconjugate of PMBS-OVA formed polymolecular associations in aqueous solution. The PMBS-OVA conjugate that contained a greater amount of PMBS delivered OVA into the cytosol at 4 °C, which is a condition that inhibits the endocytic pathway. Although the PMBS-OVA conjugate did not affect cytokine production, it increased antigen presentation via major histocompatibility complex class I. Therefore, we successfully prepared a bioconjugate that exhibits excellent biocompatibility and cans directly deliver a protein into the cytosol using phospholipid polymers.