Sivanesan Divya, Verma Rama S, Prasad Edamana
Department of Biotechnology, Indian Institute of Technology Madras Chennai-600036 India
Department of Chemistry, Indian Institute of Technology Madras Chennai-600036 India
RSC Adv. 2021 May 25;11(31):18984-18993. doi: 10.1039/d1ra01722e. eCollection 2021 May 24.
The majority of anti-cancer drugs fail to reach clinical trials due to their low water solubility. A biocompatible drug delivery system that encapsulates and efficiently delivers hydrophobic drugs to the target site is the need of the hour. This study addresses the issue by focusing on a polymeric polyglycerol sebacate (PGS) nanoparticles loaded with 5-fluorouracil (5FU), a primary line chemotherapy drug for many types of cancers. The generated nanoparticle (PGS-NP) was biocompatible and had minimal cytotoxicity against the MDA-MB-231 and A549 cell lines, even at a high concentration of 100 μg mL. The cell viability post treatment with PGS nanoparticles encapsulated with 5FU (PGS-5FU) decreased to as low as around 40% whereas, in the case of treatment with 5FU, the viability percentage increased. The nanoparticles also showed controlled drug release when encapsulated with 5FU. This striking observation suggested that these nanoparticles can improve the efficacy of drug delivery to tumor sites. Apoptosis assay and caspase-3 activity quantification supported these data wherein PGS-5FU treatment showed almost three times caspase-3 activity as compared to control cells. Additionally, throughout all the experiments, MDA-MB-231 cells were more sensitive to PGS-5FU than A549 cells, indicating that these nanoparticles are ideal for breast cancer treatment. In summary, 5FU encapsulated PGS nanoparticles are a potential drug carrier to deliver 5FU efficiently to cancer cells.
由于大多数抗癌药物水溶性低，无法进入临床试验。因此，亟需一种生物相容性药物递送系统，能够包裹并有效地将疏水性药物递送至靶位点。本研究聚焦于负载5-氟尿嘧啶（5FU）的聚癸二酸甘油酯（PGS）聚合物纳米颗粒，以解决这一问题。5FU是多种癌症的一线化疗药物。所制备的纳米颗粒（PGS-NP）具有生物相容性，即使在100 μg/mL的高浓度下，对MDA-MB-231和A549细胞系的细胞毒性也极小。用包裹了5FU的PGS纳米颗粒（PGS-5FU）处理后的细胞活力降至约40%，而用5FU处理时，活力百分比则升高。当包裹5FU时，纳米颗粒还表现出药物的可控释放。这一显著发现表明，这些纳米颗粒可以提高药物向肿瘤部位的递送效果。凋亡分析和caspase-3活性定量支持了这些数据，其中PGS-5FU处理显示出的caspase-3活性几乎是对照细胞的三倍。此外，在所有实验中，MDA-MB-231细胞对PGS-5FU比A549细胞更敏感，表明这些纳米颗粒是乳腺癌治疗的理想选择。总之，包裹5FU的PGS纳米颗粒是一种将5FU有效递送至癌细胞的潜在药物载体。
