TFP-dPEG®13-DSPE, product number 11029 (PN11029), is designed for use in liposomes and micelles. The lipophilic end of the molecule is the lipid 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) modified by conjugation to a single molecular weight, discrete polyethylene glycol (dPEG®) chain. The dPEG® spacer is functionalized as a 2,3,5,6-tetrafluorophenyl (TFP) ester. The TFP ester reacts with primary or secondary amines to form amide bonds, allowing for surface modification of a liposome or micelle with peptides, proteins, or small molecule drugs.

Liposomes and Micelles

As carriers of cytotoxic agents, labels, and imaging agents, liposomes and micelles have revolutionized pharmaceutics and medical diagnostics. Operating either passively or actively through ligand-receptor targeting, liposomal and micellar nanoparticles with diameters of 30 – 200 nm possess several desirable features for payload delivery. These features include good stability in vivo and in vitro; extended circulation in the bloodstream, increased tumor accumulation through the enhanced permeability and retention (EPR) effect; and reduced systemic toxicity, since cytotoxic agents are sequestered from cells until delivery through membrane fusion. To date, several different liposomal and micellar formulations have been approved for clinical use.

In vivo, liposomes and micelles used as nanocarriers are susceptible to opsonization and removal from the bloodstream through the RES, also known as the mononuclear phagocytic system (MPS). Polyethylene glycol (PEG) is the most commonly used surface coating of liposomes and micelles. A sufficiently dense coating of PEG creates a hydrophilic, flexible, steric barrier around the PEGylated liposomes and micelles, thus preventing opsonization and removal by the RES. Consequently, liposomes and micelles circulate longer in the bloodstream, which results in lower dosing requirements.

PEGylation of Liposomes and Micelles

Traditional PEG is a polymer. Accordingly, polymeric PEG is dispersed (Đ > 1) and consists of a complex mixture of different chain lengths and molecular weights. In contrast, Quanta BioDesign’s dPEG® products are single molecular weight compounds. Each dPEG® product contains a single, discrete PEG chain (Đ = 1). This results in a uniform product that is easier to analyze and use. To learn more about out dPEG® products, please click here. For answers to our frequently asked questions, please click here.

Traditionally liposomes and micelles are coated with polymeric PEG2000 (a polymer PEG having an average molecular weight of 2,000 Daltons) at a density of about 5 – 8 mole%. Three papers from the lab of Başar Bilgiçer at the University of Notre Dame demonstrate that this traditional PEG coating is not scientifically well reasoned. Using Quanta BioDesign’s dPEG® products, two papers by Stefanik, et al., and one paper by Noble, et al., analyze systematically the effect of different PEG chain lengths and different degrees of PEGylation of liposomes. The results of this research demonstrate that smaller, dPEG® coatings provide PEGylated liposomes with levels of protection similar to polymeric DSPE-PEG2000. Furthermore, liposomes modified with dPEG® coatings showed superior uptake of PEGylated liposomes as compared to liposomes prepared with traditional polymeric DSPE-PEG2000.

PN11029, TFP-dPEG®13-DSPE

With TFP-dPEG®13-DSPE, PN11029, the phospholipid DSPE is modified by addition of a reactive TFP ester-terminated dPEG® that is 43 atoms (50.0 Å) long. By design, the dPEG® spacer provides discrete PEG surface coating for liposomes and micelles that protects them from opsonization and removal by the RES. Moreover, the terminal TFP ester is designed to permit conjugation of PN11029 to a primary or secondary amine with a ligand such as a targeting peptide, antibody, or antibody fragment. TFP esters are particularly useful for this as they react more readily with amines and are more resistant to hydrolysis than N-hydroxysuccinimide (NHS) esters. See, TFP Esters Have More Hydrolytic Stability and Greater Reactivity Than NHS Esters.

In addition, reasoning from the data in the above-mentioned papers from the Bilgiçer lab, TFP-dPEG®13-DSPE can be mixed with other DSPE products from Quanta BioDesign that are coated with slightly shorter dPEG® spacers and terminated with non-reactive groups (for example, methoxy).

If you need bulk product in a larger package size than our standard sizes, please contact us for a quote. Our commercial capabilities permit us to manufacture this product at any scale that you need.

Application References:

  1. Hermanson, G. T. Chapter 18, PEGylation and Synthetic Polymer Modification. Bioconjugate Techniques, 3rd edition. Academic Press: New York, 2013, 787-838. Click here now for a review of Greg’s book and a link to purchase it.
  2. Hermanson, G. T. Chapter 21, Liposome Conjugates and Derivatives. Bioconjugate Techniques, 3rd edition. Academic Press: New York, 2013, 921-949.
  3. Stefanick, J. F.; Ashley, J. D.; Kiziltepe, T.; Bilgicer, B. A Systematic Analysis of Peptide Linker Length and Liposomal Polyethylene Glycol Coating on Cellular Uptake of Peptide-Targeted Liposomes. ACS Nano 2013, 7(4), 2935–2947.
  4. Stefanick, J. F.; Ashley, J. D.; Bilgicer, B. Enhanced Cellular Uptake of Peptide-Targeted Nanoparticles through Increased Peptide Hydrophilicity and Optimized Ethylene Glycol Peptide-Linker Length. ACS Nano 2013, 7(9), 8115–8127.
  5. Noble, G. T.; Stefanick, J. F.; Ashley, J. D.; Kiziltepe, T.; Bilgicer, B. Ligand-Targeted Liposome Design: Challenges and Fundamental Considerations. Trends in Biotechnology 2014, 32(1), 32–45.
  6. Saw, P. E.; Park, J.; Lee, E.; Ahn, S.; Lee, J.; Kim, H.; Kim, J.; Choi, M.; Farokhzad, O. C.; Jon, S. Effect of PEG Pairing on the Efficiency of Cancer-Targeting Liposomes. Theranostics 2015, 5(7), 746–754.
  7. Bulbake, U.; Doppalapudi, S.; Kommineni, N.; Khan, W. Liposomal Formulations in Clinical Use: An Updated Review. Pharmaceutics 2017, 9(2), 12.

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