Folate Conjugated Polyethylene Glycol Probe for Tumor-Targeted Drug Delivery of 5-Fluorouracil

Abstract

A targeted delivery system is primarily intended to carry a potent anticancer drug to specific tumor sites within the bodily tissues. In the present study, a carrier system has been designed using folic acid (FA), bis-amine polyethylene glycol (PEG), and an anticancer drug, 5-fluorouracil (5-FU). FA and PEG were joined via an amide bond, and the resulting FA-PEG-NH2 was coupled to 5-FU producing folate-polyethylene glycol conjugated 5-fluorouracil (FA-PEG-5-FU). Spectroscopic techniques (UV-Vis, 1HNMR, FTIR, and HPLC) were used for the characterization of products. Prodrug (FA-PEG-5-FU) was analyzed for drug release profile (in vitro) up to 10 days and compared to a standard anticancer drug (5-FU). Folate conjugate was also analyzed to study its folate receptors (FR) mediated transport and in vitro cytotoxicity assays using HeLa cancer cells/Vero cells, respectively, and antitumor activity in tumor-bearing mice models. Folate conjugate showed steady drug release patterns and improved uptake in the HeLa cancer cells than Vero cells. Folate conjugate treated mice group showed smaller tumor volumes; specifically after the 15th day post-treatment, tumor sizes were decreased significantly compared to the standard drug group (5-FU). Molecular docking findings demonstrated importance of Trp138, Trp140, and Lys136 in the stabilization of flexible loop flanking the active site. The folic acid conjugated probe has shown the potential of targeted drug delivery and sustained release of anticancer drug to tumor lesions with intact antitumor efficacy.

CD44 targeted delivery of oncolytic Newcastle disease virus encapsulated in thiolated chitosan for sustained release in cervical cancer: a targeted immunotherapy approach

“…To support our strategy of choosing CD44 as a potential receptor for effective antitumor targeting in cervical cancer specifically, the role of CD44 expression in cervical cancer in overall survival and disease-free survival of patients was also analyzed. As reported, folate receptor targeting by polyethylene glycol probe for 5-Fluorouracil was evaluated using bioinformatic analysis like molecular docking studies and MD simulation prior to preparation of the nanoconjugates ( 34 ). The efficacy of various pharmacological compounds was studied against CCND1(human D-type cyclin gene)/CDK4 (Cyclin-dependent kinase 4)/PLK1 (polo like kinase 1)/CD44 using various bioinformatic tools and the results showed CD44 as a highly promising antitumor target in different solid tumors ( 35 ).…”

Current development of theragnostic nanoparticles for women’s cancer treatment

“…This led to the encapsulation of 5-FU drug in the micelles and the formation of folate-polyethylene glycol conjugated 5-fluorouracil (FA-PEG-5-FU). In vitro cytotoxicity assays and antitumor activity in tumor-bearing mice models of the drug were done using HeLa cancer cells/Vero cells (Sarwar et al 2022).…”

Material and Design Toolkit for Drug Delivery: State of the Art, Trends, and Challenges

“…Sarwar et al developed a nanocarrier system using FA bis-amine PEG, and an anticancer drug, 5-fluorouracil (5-FU). 234 FA and PEG were joined via an amide bond, and the resulting FA-PEG-NH 2 was coupled to 5-FU-producing folate-polyethylene glycol conjugated 5-fluorouracil (FA-PEG-5-FU). The in vivo experiment on mice suggested that the folate conjugate treated mice showed fewer tumor volumes, specifically after the 15th-day post-treatment.…”

“…The use of FA as a target ligand has several advantages, such as (i) ease of conjugation to both diagnostic and therapeutic agents, (ii) high affinity for the FR, and (iii) the distribution of FRs in limited numbers in normal tissues. Sarwar et al developed a nanocarrier system using FA bis-amine PEG, and an anticancer drug, 5-fluorouracil (5-FU) . FA and PEG were joined via an amide bond, and the resulting FA-PEG-NH 2 was coupled to 5-FU-producing folate-polyethylene glycol conjugated 5-fluorouracil (FA-PEG-5-FU).…”