Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center of RAS, Kazan 420111, Russia.
Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan 420008, Russia.
Int J Mol Sci. 2023 Jan 4;24(2):926. doi: 10.3390/ijms24020926.
Therapy of colorectal cancer with protein drugs, including targeted therapy using monoclonal antibodies, requires the preservation of the drug's structure and activity in the gastrointestinal tract or bloodstream. Here, we confirmed experimentally the fundamental possibility of creating composite protein-polysaccharide hydrogels based on non-degrading rhamnogalacturonan I (RG) and fibrin as a delivery vehicle for antitumor RNase binase. The method is based on enzymatic polymerization of fibrin in the presence of RG with the inclusion of liposomes, containing an encapsulated enzyme drug, into the gel network. The proposed method for fabricating a gel matrix does not require the use of cytotoxic chemical cross-linking agents and divalent cations, and contains completely biocompatible and biodegradable components. The process proceeds under physiological conditions, excluding the effect of high temperatures, organic solvents and ultrasound on protein components. Immobilization of therapeutic enzyme binase in the carrier matrix by encapsulating it in liposomes made from uncharged lipid made it possible to achieve its prolonged release with preservation of activity for a long time. The release time of binase from the composite carrier can be regulated by variation of the fibrin and RG concentration.
用于治疗结直肠癌的蛋白质药物，包括使用单克隆抗体的靶向治疗，需要在胃肠道或血液中保持药物的结构和活性。在这里，我们通过实验证实了基于非降解鼠李半乳糖醛酸聚糖 I（RG）和纤维蛋白的复合蛋白-多糖水凝胶作为抗肿瘤 RNase binase 递送载体的基本可能性。该方法基于在 RG 存在下纤维蛋白的酶聚合，将包含包封酶药物的脂质体纳入凝胶网络中。所提出的制造凝胶基质的方法不需要使用细胞毒性化学交联剂和二价阳离子，并且包含完全生物相容和可生物降解的成分。该过程在生理条件下进行，排除了高温、有机溶剂和超声对蛋白质成分的影响。通过将治疗酶 binase 包封在由不带电荷的脂质制成的脂质体中来固定在载体基质中，使其能够长时间保持活性的长时间释放。通过改变纤维蛋白和 RG 的浓度可以调节 binase 从复合载体中的释放时间。
