l-Asparaginase Immobilized on Nanographene Oxide as an Efficient Nanobiocatalytic Tool for Asparagine Depletion in Leukemia Cells.

in Bioconjugate chemistry by Paulina Erwardt, Bartosz Szymczak, Marek Wiśniewski, Bartosz Maciejewski, Michał Świdziński, Janusz Strzelecki, Wiesław Nowak, Katarzyna Roszek

TLDR

  • Researchers developed a novel enzyme-based therapy using immobilized l-asparaginase on nanostructured graphene oxide to target leukemia cells, showing potential for improved treatment options.

Abstract

l-Asparaginase (l-ASNase) catalyzes the hydrolysis of l-asparagine, leading to its depletion and subsequent effects on the cellular proliferation and survival. In contrast to normal cells, malignant cells that lack asparagine synthase are extremely susceptible to asparagine deficiency. l-ASNase has been successfully employed in treating pediatric leukemias and non-Hodgkin lymphomas; however, its usage in adult patients and other types of cancer is limited due to significant side effects and drug resistance. Recent research has explored alternative formulations and delivery methods to enhance its efficacy and minimize adverse effects. One promising approach involves the immobilization of l-ASNase onto nanostructured materials, offering improved enzymatic activity and biocompatibility of the support. We harnessed anl-ASNase type II preparation to develop a novel strategy of enzyme immobilization on graphene oxide (GO)-based support. We compared GO and nanographene oxide (nGO) in terms of their biocompatibility and influence on enzyme parameters. The obtained l-ASNase on the nGO nanobiocatalyst maintains enzymatic activity and increases its stability, selectively acting on K562 leukemia cells without cytotoxic influence on normal endothelial cells. In the case of treated K562 cells, we confirmed enlargement in the cell and nucleus size, disturbance in the cell cycle (interphase and metaphase), and increased apoptosis rate. The potential therapeutic possibilities of immobilized l-ASNase on leukemia cell damage are also discussed, highlighting the importance of further research in this area for advancing cancer therapy.

Overview

  • The study focuses on the development of a novel strategy for l-asparaginase (l-ASNase) immobilization on nanostructured materials for improved efficacy and reduced side effects in cancer treatment.
  • The study compares the biocompatibility and influence of graphene oxide (GO) and nanographene oxide (nGO) on enzyme parameters and activity.
  • The primary objective is to develop an improved enzyme-based therapy for treating leukemia and other types of cancer by harnessing the immunolized l-ASNase on nGO nanobiocatalyst.

Comparative Analysis & Findings

  • The study finds that the immobilized l-ASNase on nGO nanobiocatalyst maintains enzymatic activity and increases stability, selectively acting on K562 leukemia cells without cytotoxic effects on normal endothelial cells.
  • The study reports that treated K562 cells exhibit noticeable changes, including enlarged cell and nucleus size, disruption in cell cycle, and increased apoptosis rate.
  • The findings suggest that the immobilized l-ASNase on nGO nanobiocatalyst has potential therapeutic possibilities for leukemia treatment, highlighting the need for further research to advance cancer therapy.

Implications and Future Directions

  • The study demonstrates the potential of enzyme-based therapy for cancer treatment, particularly in leukemia, and highlights the importance of continued research in this area.
  • Future studies should focus on optimizing the immobilization strategy and exploring its efficacy in various types of cancer.
  • The study's findings have implications for the development of new cancer therapies and may lead to improved treatment options for patients with leukemia and other types of cancer.
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