Kazi Julekha, Mukhopadhyay Ria, Sen Ramkrishna, Jha Tarun, Ganguly Shantanu, Debnath Mita Chatterjee
Infectious Diseases and Immunology Division , CSIR-Indian Institute of Chemical Biology , Kolkata , India . Email:
Department of Pharmaceutical Technology , Jadavpur University , Kolkata , India.
Medchemcomm. 2019 Mar 12;10(4):559-572. doi: 10.1039/c8md00565f. eCollection 2019 Apr 1.
In the present investigation folate peptide (FA-Pep) conjugated 5-fluorouracil (5-FU) loaded nanoparticles were synthesized and their tumor targeting potentiality was monitored by different and techniques. FA-Pep-1 and FA-Pep-2 were synthesized and radiolabeled with Tc(CO)(HO). Tc(CO)-FA-Pep-1 exhibited promising tumor uptake in an model (nude mice bearing HeLa cell xenograft and Balb/c mice bearing B16F10 melanoma tumor) as compared to Tc(CO)-FA-Pep-2. FA-Pep-1 was then conjugated with 5-FU-NPs (118 ± 4.3), as confirmed by the XPS study. These showed promising cytotoxic and apoptotic potential in B16F10 cell lines as compared to free 5-FU and unconjugated 5-FU-NPs. biodistribution and gamma-scintigraphy showed good accumulation of peptide conjugated NPs in the tumor region. Therapeutic efficacy studies in B16F10 tumor xenografts also exhibited substantial tumor growth inhibition. The above studies reveal that folate peptide conjugation may facilitate the tumor-targeting approach of 5-FU-NPs.
在本研究中，合成了叶酸肽（FA-Pep）偶联负载5-氟尿嘧啶（5-FU）的纳米颗粒，并通过不同的技术监测其肿瘤靶向潜力。合成了FA-Pep-1和FA-Pep-2并用Tc(CO)(HO)进行放射性标记。与Tc(CO)-FA-Pep-2相比，Tc(CO)-FA-Pep-1在动物模型（荷HeLa细胞异种移植瘤的裸鼠和荷B16F10黑色素瘤肿瘤的Balb/c小鼠）中表现出有前景的肿瘤摄取。然后通过XPS研究证实，FA-Pep-1与5-FU纳米颗粒（118±4.3）偶联。与游离5-FU和未偶联的5-FU纳米颗粒相比，这些在B16F10细胞系中显示出有前景的细胞毒性和凋亡潜力。生物分布和γ闪烁显像显示肽偶联纳米颗粒在肿瘤区域有良好的聚集。对B16F10肿瘤异种移植瘤的治疗效果研究也显示出显著的肿瘤生长抑制。上述研究表明，叶酸肽偶联可能有助于5-FU纳米颗粒的肿瘤靶向方法。
