Folate PEG

Folate PEG has gained considerable attention in oncology due to its ability to selectively target cancer cells that overexpress folate receptors. Folate receptors are highly expressed on the surface of many cancer cells, making them an attractive target for specifically delivering anticancer drugs to tumor cells while minimizing systemic toxicity. By combining folic acid with PEG, researchers have been able to create drug delivery systems that can specifically target cancer cells. For example, folic acid-polyethylene glycol (PEG)-modified liposomes can enhance stability and tumor targeting, improve the anti-tumor effect of baicalin, and are an effective targeting carrier system.

BOC Sciences, a leading provider of research chemicals and custom synthesis services, offers high-quality folate PEG products designed to enhance the delivery of therapeutics to specific cells expressing folate receptors. Our PEG products are available in a variety of molecular weights and configurations to meet the specific needs of researchers and pharmaceutical companies. We support custom conjugation of folic acid to PEG to optimize pharmacokinetics, biodistribution, and targeting efficiency of the final product.

What is Folate (Folic Acid)?

Folic acid is a water-soluble B vitamin that plays a vital role in various biological processes in the body, including DNA synthesis, repair, and methylation. The body cannot synthesize folic acid and must obtain it through diet or supplements. It is essential for the production of nucleic acids, the building blocks of DNA and RNA. Through a series of enzymatic reactions in the body, folate is converted into its active form, tetrahydrofolate (THF). THF plays a key role in the transfer of one-carbon units during DNA, RNA, and amino acid synthesis. This process is essential for cell division, growth and repair, so folate is essential for normal physiological functions.

Folate PEG in Drug Delivery

The combination of folic acid with PEG offers several advantages for targeted drug delivery. The PEG component provides water solubility and stability to the compound, thereby extending blood circulation and enhancing tumor penetration. In addition, folate ligands promote specific binding of compounds to folate receptors on cancer cells, thereby increasing drug uptake in the tumor microenvironment. One of the key features of folate PEG is its ability to overcome multidrug resistance in cancer cells. Multidrug resistance is a common phenomenon in cancer treatment, in which cancer cells become resistant to multiple chemotherapy drugs, leading to treatment failure. Folate PEG has been shown to bypass the efflux pumps responsible for cancer cell drug resistance, thereby increasing intracellular drug accumulation and improving treatment outcomes.

Fig. 1. Application of folic acid-PEG conjugates in cancer therapy (ACS Omega. 2017, 2(10): 6349-6360).

In addition to its use in cancer treatment, folic acid PEG has shown promise in treating other diseases, such as inflammatory diseases, autoimmune diseases, and infectious diseases. Targeted delivery of therapeutics using folic acid PEG can enhance therapeutic efficacy while minimizing off-target effects, making it a versatile platform for precision medicine.

Folate-PEG Conjugates

The development of folate PEG-based drug delivery systems involves the design and synthesis of novel conjugates to optimize drug loading, stability, and targeting efficiency. Various strategies have been used to conjugate folic acid to PEG, including chemical conjugation, biological conjugation, and self-assembly techniques. These methods allow tailoring of folate PEG conjugates to meet the specific requirements of different therapeutic applications. The pharmacokinetic properties of Folate PEG can be further optimized by varying the molecular weight and structure of the PEG components. By adjusting the size and flexibility of the PEG chains, researchers can control the circulation time, biodistribution, and tumor accumulation of folate PEG conjugates, thereby improving their overall therapeutic efficacy.

Folate-PEG-Amine

Folate-PEG-Amine is a compound composed of folic acid, PEG and amine groups. The amine groups in the formula can be used for further functionalization or conjugation of drugs or imaging agents, thereby increasing the versatility of the system. The presence of folic acid can specifically target folate receptor-expressing cells, making it a valuable tool for precision medicine applications. PEGylation endows folate-PEG-amine with invisibility and stability, thereby prolonging the circulation time and reducing the immunogenicity. The flexibility of amine groups provides an opportunity to customize nano-preparations for specific therapeutic or diagnostic purposes.

DSPE-PEG-Folate

DSPE-PEG-Folate is a nano-preparation composed of DSPE (1,2-distearoyl-sn-glycerol-3-phosphate ethanolamine), PEG and folic acid. The PEG incorporated in DSPE-PEG-Folate provides invisible properties by reducing the recognition and clearance of the immune system, thereby prolonging the circulation time in the blood. In addition, PEGylation enhances the stability of nano-preparations and prevents aggregation under physiological conditions. DSPE contributes to the formation of lipid bilayers, which can encapsulate hydrophobic drugs for delivery to target cells.

PLGA-PEG-Folate

PLGA-PEG-Folate is another nano-preparation that combines PLGA (poly lactic-co-glycolic acid), PEG and folic acid. PLGA is a biodegradable and biocompatible polymer that is widely used in drug delivery systems due to its adjustable degradation kinetics and ability to encapsulate multiple drugs. The addition of PEG improved the hydrophilicity of the nano-preparation and enhanced its stability in the biological environment. Similar to DSPE-PEG-Folate, the presence of folic acid in PLGA-PEG-Folate can be targeted to folate receptor-expressing cells, such as cancer cells.

Case Study

Sarwar et al. designed a drug carrier system using folic acid (FA), diamine polyethylene glycol (Amine-PEG-Amine), and the anticancer drug 5-fluorouracil (5-FU). FA and PEG are connected through an amide bond, and the resulting FA-PEG-NH is coupled with 5-FU to produce folic acid-polyethylene glycol conjugated 5-fluorouracil (FA-PEG-5-FU). The prodrug (FA-PEG-5-FU) was analyzed for drug release profiles (in vitro) up to 10 days and compared with a standard anticancer drug (5-FU). Folate conjugates were also analyzed to study their folate receptor (FR)-mediated transport and in vitro cytotoxicity assay using HeLa cancer cells/Vero cells, respectively, as well as antitumor activity in tumor-bearing mouse models. Folate conjugates exhibited stable drug release patterns and improved uptake in HeLa cancer cells compared to Vero cells. Mice in the folic acid conjugate-treated group had smaller tumor sizes; especially at day 15 after treatment, tumor size was significantly reduced compared to the standard drug group (5-FU). Molecular docking results demonstrate the importance of Trp138, Trp140, and Lys136 in the stabilization of the flexible loops flanking the active site. Folate-conjugated probes show potential for targeted drug delivery and sustained release of anticancer drugs to tumor lesions with complete antitumor efficacy.^[2]

References

1. You, Y. et al. Folate-PEG Conjugates of a Far-Red Light-Activatable Paclitaxel Prodrug to Improve Selectivity toward Folate Receptor-Positive Cancer Cells. ACS Omega. 2017, 2(10): 6349-6360.
2. Sarwar, S. et al. Folate Conjugated Polyethylene Glycol Probe for Tumor-Targeted Drug Delivery of 5-Fluorouracil. Molecules. 2022, 27(6): 1780.