Department of Gynecology, The First Hospital of Jilin University, Changchun 130021, China.
Department of Sports Medicine, Orthopaedics Clinic, The First Hospital of Jilin University, Changchun 130021, China.
Colloids Surf B Biointerfaces. 2024 Apr;236:113795. doi: 10.1016/j.colsurfb.2024.113795. Epub 2024 Feb 16.
Overexpression of epidermal growth factor receptor (EGFR) in cancer is a key cause of recurrence of cervical cancer (CC). Although the EGF-EGFR pathway has been studied for decades, preventing tumor growth and recurrence caused by peripheral EGF remains a great challenge. In this work, a strategy is proposed to reduce the stimulation of high concentration EGF on tumor growth by using a thermo-sensitive hydrogel. The hydrogel is a triblock copolymer composed of polyethylene glycol (PEG) and poly (lactide glycolide) (PLGA). Based on the excellent temperature sensitivity, carrier capacity, swelling property and biocompatibility, the hydrogel can absorb the liquid around the tumor by injection and release EGF continuously at low concentration. The inhibitory effect of hydrogel on tumor growth is fully confirmed by an implanted tumor mouse model with human cervical cancer cell lines (HeLa) using triple-immunodeficient NCG mice. Compared with free EGF, the EGF-loaded hydrogel can hardly induce surface plasmon resonance (SPR) response, which proves that hydrogel can effectively weaken cytoskeleton rearrangement and inhibit cell migration by continuously releasing low concentration EGF. In addition, the EGF-loaded hydrogel can reduce cell proliferation by delaying the progress of cell cycle progression. Taken together, the hydrogel can effectively protect tumor microenvironment from the stimulation of high concentration EGF, delay cancer cellular processes and tumor growth, and thus providing an approach for inhibiting tumor recurrence of CC.
表皮生长因子受体（EGFR）在癌症中的过度表达是宫颈癌（CC）复发的一个关键原因。尽管 EGF-EGFR 通路已经研究了几十年，但防止外周 EGF 引起的肿瘤生长和复发仍然是一个巨大的挑战。在这项工作中，提出了一种利用热敏水凝胶来减少高浓度 EGF 对肿瘤生长刺激的策略。该水凝胶是一种由聚乙二醇（PEG）和聚（乳酸-乙醇酸）（PLGA）组成的三嵌段共聚物。基于其优异的温度敏感性、载药能力、溶胀性能和生物相容性，水凝胶可以通过注射吸收肿瘤周围的液体，并以低浓度持续释放 EGF。通过使用三重免疫缺陷 NCG 小鼠植入人宫颈癌细胞系（HeLa）的肿瘤小鼠模型，充分证实了水凝胶对肿瘤生长的抑制作用。与游离 EGF 相比，负载 EGF 的水凝胶几乎不能诱导表面等离子体共振（SPR）响应，这证明水凝胶可以通过持续释放低浓度 EGF 有效地削弱细胞骨架重排并抑制细胞迁移。此外，负载 EGF 的水凝胶可以通过延迟细胞周期进程来减少细胞增殖。总之，水凝胶可以有效地保护肿瘤微环境免受高浓度 EGF 的刺激，延缓癌症细胞过程和肿瘤生长，从而为抑制 CC 的肿瘤复发提供了一种方法。
