Bacterial Cellulose-Chitosan Composite for Prolonged-Action L-Asparaginase in Treatment of Melanoma Cells

---

Anastasia N. Shishparenok¹, Egor R. Petryaev², Svetlana A. Koroleva³, Natalya V. Dobryakova¹, Igor D. Zlotnikov⁴, Elena N. Komedchikova⁵, Olga A. Kolesnikova⁵, Elena V. Kudryashova⁴, Dmitry D. Zhdanov^1,a*

¹Institute of Biomedical Chemistry, 119121 Moscow, Russia

²Moscow Polytechnic University, 107023 Moscow, Russia

³Patrice Lumumba Peoples’ Friendship University of Russia (RUDN University), 117198 Moscow, Russia

⁴Faculty of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia

⁵Moscow Institute of Physics and Technology (National Research University), 141701 Dolgoprudny, Moscow Region, Russia

^* To whom correspondence should be addressed.

Received: May 30, 2024; Revised: July 12, 2024; Accepted: July 22, 2024

---

A significant challenge associated with the therapeutic use of L-ASP for treatment of tumors is its rapid clearance from plasma. Effectiveness of L-ASP is limited by the dose-dependent toxicity. Therefore, new approaches are being developed for L-ASP to improve its therapeutic properties. One of the approaches to improve properties of the enzymes, including L-ASP, is immobilization on various types of biocompatible polymers. Immobilization of enzymes on a carrier could improve stability of the enzyme and change duration of its enzymatic activity. Bacterial cellulose (BC) is a promising carrier for various drugs due to its biocompatibility, non-toxicity, high porosity, and high drug loading capacity. Therefore, this material has high potential for application in biomedicine. Native BC is known to have a number of disadvantages related to structural stability, which has led to consideration of the modified BC as a potential carrier for immobilization of various proteins, including L-ASP. In our study, a BC–chitosan composite in which chitosan is cross-linked with glutaraldehyde was proposed for immobilization of L-ASP. Physicochemical characteristics of the BC–chitosan films were found to be superior to those of native BC films, resulting in increase in the release time of L-ASP in vitro from 8 to 24 h. These films exhibited prolonged toxicity (up to 10 h) against the melanoma cell line. The suggested strategy for A-ASP immobilization on the BC–chitosan films could be potentially used for developing therapeutics for treatment of surface types of cancers including melanomas.

---

KEY WORDS: L-asparaginase, bacterial cellulose, chitosan, kinetic models, cytotoxicity, melanoma

DOI: 10.1134/S0006297924100067

Publisher’s Note. Pleiades Publishing remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

---