Design of 5-fluorouracil (5-FU) loaded, folate conjugated peptide linked nanoparticles, a potential new drug carrier for selective targeting of tumor cells.

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 in vitro and in vivo techniques. FA-Pep-1 and FA-Pep-2 were synthesized and radiolabeled with 99mTc(CO)3(H2O)3. 99mTc(CO)3-FA-Pep-1 exhibited promising tumor uptake in an in vivo model (nude mice bearing HeLa cell xenograft and Balb/c mice bearing B16F10 melanoma tumor) as compared to 99mTc(CO)3-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. In vivo 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.