PEG-Conjugates of Folic Acid and Cholesterol

PEG-Conjugates of Folic Acid and Cholesterol

Published on 30.09.2016

Conjugates of PEG and folic acid or cholesterol, respectively, combine the positive properties of these molecules. Those conjugates are available with a wide variety of functional groups and different PEG chain lengths to suit your needs.

Folic acid (FA) is one of the B vitamins (vitamin B9) and is an essential nutrient. Folic acid deficiency may lead to symptoms such as headaches, depression, forgetfulness and other cognitive deficits, nerve damage, heart palpitations and pregnancy complications. Folic acid is recognized and internalized by folate receptors, which are overexpressed on the cell surface of certain tumor types.

Cholesterol (CLS) is a lipid that is an integral component of all animal cell membranes. It is required to maintain both membrane structural integrity and fluidity, and thus is essential for all animal life. Cholesterol also serves as a precursor for the biosynthesis of steroid hormones and bile acids and is involved in many other biological functions.

Folic Acid (left) and Cholesterol (right).

PEG conjugates of folic acid and cholesterol are valuable tools for the delivery of drugs and other molecules, such as fluorophores. While the folic acid moiety is commonly used to target folate receptors, PEG-cholesterol conjugates promote internalization via clathrin-independent pathways into endosomes and the Golgi apparatus. Furthermore, the PEG chain drastically improves solubility as well as physical stability and half-life in vivo.

Iris Biotech now offers many variants of PEG-conjugates of FA and CLS, equipped with a wide variety of functional groups to suit your needs (amine, NHS ester, azide, thiol etc.). Moreover, each of these derivatives is offered with PEG chains of different lengths, ranging from 1’000 Da to 20’000 Da. We also offer cross-linked PEG-conjugates of both cholesterol and folic acid (FA-PEG-CLS), which combine the benefits of those moieties.

→ Find all of our PEG-Conjugates, as well as many other PEGylation reagents, in our Webshop!

References

  • Curcumin entrapped folic acid conjugated PLGA-PEG nanoparticles exhibit enhanced anticancer activity by site specific delivery; J. J. Pillai, A. K. T. Thulasidasan, R. J. Anto, N. C. Devika, N. Ashwanikumar and G. S. V. Kumar; RSC Advances 2015; 5: 25518-25524. doi:10.1039/c5ra00018a
  • Folate-conjugated nanoparticles as a potent therapeutic approach in targeted cancer therapy; B. Bahrami, M. Mohammadnia-Afrouzi, P. Bakhshaei, Y. Yazdani, G. Ghalamfarsa, M. Yousefi, S. Sadreddini, F. Jadidi-Niaragh and M. Hojjat-Farsangi; Tumor Biology 2015; 36: 5727-5742. doi:10.1007/s13277-015-3706-6
  • Defined Folate-PEG-siRNA Conjugates for Receptor-specific Gene Silencing; C. Dohmen, T. Frohlich, U. Lachelt, I. Rohl, H.-P. Vornlocher, P. Hadwiger and E. Wagner; Mol Ther Nucleic Acids 2012; 1: e7. doi:10.1038/mtna.2011.10
  • Utilizing the folate receptor for active targeting of cancer nanotherapeutics; G. L. Zwicke, G. A. Mansoori and C. J. Jeffery; 2012 2012. doi:10.3402/nr.v3i0.18496
  • A Comparative Study of Two Folate-Conjugated Gold Nanoparticles for Cancer Nanotechnology Applications; G. A. Mansoori, K. S. Brandenburg and A. Shakeri-Zadeh; Cancers 2010; 2: 1911.
  • Development of a targeted siRNA delivery system using FOL-PEG-PEI conjugate; B. K. Biswal, N. B. Debata and R. S. Verma; Molecular Biology Reports 2010; 37: 2919-2926. doi:10.1007/s11033-009-9853-3
  • Targeted drug delivery via folate receptors; X. Zhao, H. Li and R. J. Lee; Expert Opinion on Drug Delivery 2008; 5: 309-319. doi:10.1517/17425247.5.3.309
  • Tumor detection using folate receptor-targeted imaging agents; E. I. Sega and P. S. Low; Cancer and Metastasis Reviews 2008; 27: 655-664. doi:10.1007/s10555-008-9155-6
  • The folate receptor: What does it promise in tissue-targeted therapeutics?; M. D. A. Salazar and M. Ratnam; Cancer and Metastasis Reviews 2007; 26: 141-152. doi:10.1007/s10555-007-9048-0
  • Folic acid-PEG conjugated superparamagnetic nanoparticles for targeted cellular uptake and detection by MRI; C. Sun, R. Sze and M. Zhang; Journal of Biomedical Materials Research Part A 2006; 78A: 550-557. doi:10.1002/jbm.a.30781
  • Folate receptor expression in carcinomas and normal tissues determined by a quantitative radioligand binding assay; N. Parker, M. J. Turk, E. Westrick, J. D. Lewis, P. S. Low and C. P. Leamon; Analytical Biochemistry 2005; 338: 284-293. doi:http://dx.doi.org/10.1016/j.ab.2004.12.026
  • Subcellular Fate of a Fluorescent Cholesterol-Poly(ethylene glycol) Conjugate: An Excellent Plasma Membrane Imaging Reagent; X. Chen, X. Zhang, H.-Y. Wang, Z. Chen and F.-G. Wu; Langmuir 2016. doi:10.1021/acs.langmuir.6b02288
  • Recent development of poly(ethylene glycol)-cholesterol conjugates as drug delivery systems; Z.-Y. He, B.-Y. Chu, X.-W. Wei, J. Li, C. K. Edwards Iii, X.-R. Song, G. He, Y.-M. Xie, Y.-Q. Wei and Z.-Y. Qian; International Journal of Pharmaceutics 2014; 469: 168-178. doi:http://dx.doi.org/10.1016/j.ijpharm.2014.04.056
  • Preparation of long-circulating immunoliposomes using PEG–cholesterol conjugates: effect of the spacer arm between PEG and cholesterol on liposomal characteristics; C. Carrion, J. C. Domingo and M. A. de Madariaga; Chemistry and Physics of Lipids 2001; 113: 97-110. doi:http://dx.doi.org/10.1016/S0009-3084(01)00178-5
  • Poly(ethylene glycol)−Lipid Conjugates Promote Bilayer Formation in Mixtures of Non-Bilayer-Forming Lipids; J. W. Holland, P. R. Cullis and T. D. Madden; Biochemistry 1996; 35: 2610-2617. doi:10.1021/bi951999j