纳米免疫治疗药物在肺癌细胞中的传递研究

C. A. Kruger, M. Mokwena, H. Abrahamse
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引用次数: 1

摘要

肺癌在世界范围内具有很高的发病率和死亡率,因此迫切需要开发新的治疗方法。光动力疗法(PDT)是一种利用光敏剂(PS)药物的光化学癌症治疗,当被特定波长的激光激活时,产生活性氧,进而诱导细胞死亡。然而,由于PSs的被动扩散,有时会影响周围的正常细胞,其在癌细胞中的靶向浓度往往很低,从而限制了这种治疗的有效性。因此,通常采用多组分药物靶向策略来提高PS在癌细胞中的特异性递送和浓度,从而提高PDT的有效性。本研究旨在通过增强锌(II)酞菁四磺酸(ZnPcS4)的化学结构,改善其在肺癌细胞中的PS药物传递。ZnPcS4成功地偶联到聚乙二醇化的金纳米颗粒上,以最大限度地提高其溶解度和稳定性,并结合到特定的活性肿瘤相关抗体抗原(Cetuximab: Anti-EGFR1 Ab)上,以帮助特异性靶向PS递送。在体外培养的肺癌细胞中,该分子给药系统改善了ZnPcS4的亚细胞定位。此外,在进行体外PDT实验后,发现大量细胞死亡和细胞毒性。总的来说,这种纳米免疫治疗药物结合ZnPcS4与AuNP和西妥昔单抗,被证明可以增强肺癌细胞对浓缩PS的摄取,从而改善这种癌症的PDT治疗效果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Investigation of nano immunotherapy drug delivery in lung cancer cells
Lung cancer has high incidence and mortality rates worldwide and so there is strong need for the development of novel therapies. Photodynamic therapy (PDT) is a photochemotherapeutic cancer treatment that utilizes a photosensitizer (PS) drug that, when activated by laser light at a specific wavelength, yields reactive oxygen species, which in turn induces cell death. However, due to the passive diffusion of PSs, normal surrounding cells are sometimes affected and their targeted concentrations in cancer cells tends to be minimal, thus limiting the effectiveness of this treatment. Therefore, a multicomponent drug targeting strategy is often applied to improve PS specific delivery and concentration in cancer cells, which in turn can improve the effectiveness of PDT. The intention of this study was to improve the PS drug delivery of Zn(II) Phthalocyanine tetrasulfonic acid (ZnPcS4) in lung cancer cells, by enhancing its chemical structure. ZnPcS4 was successfully conjugated to pegylated gold nanoparticles in order to maximize its solubility and stability, as well as bound to specific active tumour-associated antibody-antigens (Cetuximab: Anti-EGFR1 Ab) to aid specific targeted PS delivery. Within in vitro cultured lung cancer cells, this molecular drug delivery system noted improved and specific sub-cellular location of ZnPcS4. Furthermore, after conducting in vitro PDT experiments, a significant amount of cell death and cytotoxicity was found. Overall, this nano immunotherapy drug conjugation combination of ZnPcS4 with AuNP and Cetuximab, proved to enhance concentrated PS uptake in lung cancer cells and so improve PDT treatment outcomes for this form of cancer.
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