Kobylinska Lesya, Patereha Igor, Finiuk Natalia, Mitina Natalia, Riabtseva Anna, Kotsyumbas Igor, Stoika Rostyslav, Zaichenko Alexander, Vari Sandor G
1Danylo Halytsky Lviv National Medical University, Pekarska str., 69a, Lviv, 79010 Ukraine.
State Scientific-Research Control Institute of Veterinary Medicinal Products and Feed Additives, Donetska str., 11, Lviv, 79019 Ukraine.
Cancer Nanotechnol. 2018;9(1):11. doi: 10.1186/s12645-018-0045-5. Epub 2018 Dec 20.
Development of biocompatible multifunctional polymeric drug carriers is crucial in modern pharmaceutics aimed to create "smart" drugs. The high potential of the PEGylated comb-like polymeric nanocarrier (PNC) in delivering both traditional and experimental drugs to tumor cells in vitro and in vivo has been demonstrated previously. In the present study, we investigated the general toxicity of polyethylene glycol (PEG) processed with both covalent and non-covalent attachments of PEG to compose a comb-like polymer that behaves like a simple chain of n monomers decorated with swollen side chains. The PNC possesses properties of a water-soluble surfactant containing methyl-terminated PEG side branches in some monomer units attached covalently to the carbon chain backbone.
We have demonstrated that the synthesized PNC possesses weak toxic effects toward human leukemia cells (HL-60 and Jurkat lines), as well as toward hepatocellular (HepG2), colon (HCT116) and breast (MCF-7) tumor cell lines. Additionally, after a long period (20 days) of intraperitoneal administration, the PNC had no significant toxic effects in laboratory white mice (470 mg/kg body mass in 1 ml) and Wistar rats (440 mg/kg body mass in 10 ml).
The developed PNC we studied can be qualified as a compound of grade 4 toxicity (low toxicity substance). The reduced toxicity of this PNC in combination with its improved bioavailability and previously detected capability to enhance cytotoxicity toward tumor cells in vitro and potential tumor treatment effects in vivo suggests its potential as a safe drug delivery platform for treating various diseases, especially cancer.
在现代制药领域，开发生物相容性多功能聚合物药物载体对于创造“智能”药物至关重要。此前已证明聚乙二醇化梳状聚合物纳米载体（PNC）在体外和体内将传统药物和实验药物递送至肿瘤细胞方面具有很高的潜力。在本研究中，我们研究了通过共价和非共价连接聚乙二醇（PEG）制备的梳状聚合物的一般毒性，该聚合物的行为类似于由带有肿胀侧链的n个单体组成的简单链。PNC具有水溶性表面活性剂的特性，在一些单体单元中含有甲基封端的PEG侧链，这些侧链共价连接到碳链主链上。
我们已证明合成的PNC对人白血病细胞（HL-60和Jurkat细胞系）以及对肝细胞（HepG2）、结肠（HCT116）和乳腺（MCF-7）肿瘤细胞系具有微弱的毒性作用。此外，在腹腔注射较长时间（20天）后，PNC对实验室小白鼠（1ml中470mg/kg体重）和Wistar大鼠（10ml中440mg/kg体重）没有明显的毒性作用。
我们研究的已开发PNC可被归类为4级毒性化合物（低毒物质）。这种PNC毒性降低，同时具有改善的生物利用度，以及先前检测到的在体外增强对肿瘤细胞的细胞毒性和在体内潜在的肿瘤治疗效果的能力，表明其作为治疗各种疾病，尤其是癌症的安全药物递送平台的潜力。
