EGF-targeting lipodisks for specific delivery of poorly water-soluble anticancer agents to tumour cells

Abstract

Concerns regarding poor aqueous solubility, high toxicity and lack of specificity impede the translation of many hydrophobic anticancer agents into safe and effective anticancer drugs. The application of colloidal drug delivery systems, and in particular the use of lipid-based nanocarriers, has been identified as a promising means to overcome these issues. PEG-stabilized lipid nanodisks (lipodisks) have lately emerged as a novel type of biocompatible, nontoxic and adaptable drug nanocarrier. In this study we have explored the potential of lipodisks as a platform for formulation and tumour targeted delivery of hydrophobic anticancer agents. Using curcumin as a model compound, we show that lipodisks can be loaded with substantial amounts of hydrophobic drugs (curcumin/lipid molar ratio 0.15). We demonstrate moreover that by deliberate choice of preparation protocols the lipodisks can be provided with relevant amounts of targeting proteins, such as epidermal growth factor (EGF). Data from in vitro cell studies verify that such EGF-decorated curcumin-loaded lipodisks are capable of EGF-receptor specific targeting of human A-431 tumour cells, and strongly suggest that the interaction between the lipodisks and the tumour cells results in receptor-mediated internalization of the disks and their cargo.

Tumor-Targeted Delivery of the p53-Activating Peptide VIP116 with PEG-Stabilized Lipodisks

“…All lipodisks used in the study were produced with a method based on detergent depletion using Bio-Beads (SM-2 Adsorbent, Bio-rad, Sundbyberg, Sweden) in accordance with a previously described protocol [15,19]. Briefly, for lipodisks used in QCM-D assays a lipid film composed of DSPC:DSPE-PEG2000:DSPE-PEG2000-biotin 80:16:4 was prepared as described above.…”

“…Lipid bilayer disks (lipodisks) are nanosized bilayer structures, stabilized into flat, circular shapes by polyethylene glycol (PEG)-linked lipids [12][13][14]. These nanoparticles show great potential as drug carriers and have been preclinically assessed for delivery of anti-cancer and anti-bacterial compounds [13,[15][16][17][18][19]. Moreover, a targeting moiety can be attached to the lipodisk to increase delivery to desired tissues.…”

“…Epidermal growth factor receptor (EGFR) is upregulated in several cancers, and has emerged as a target for diagnostic imaging and therapy [20]. Consequently, we have developed and utilized EGFR-targeted lipodisks for delivery of different classes of anti-cancer drugs [15,19]. In the present study, we investigated the feasibility of delivering the novel p53-activating peptide VIP116 to tumor cells via EGFR-targeted lipodisks.…”

The Phospholipid Research Center: Current Research in Phospholipids and Their Use in Drug Delivery

“…Previous studies showed that a formulation in lipodisks can be used as a viable means to increase tumor accumulation and reduce off-target toxicity of both the anticancer peptide melittin and chemotherapeutic drugs, such as doxorubicin and paclitaxel [ 149 ]. Recent results from the Edwards lab showed that by decorating the lipodisks with ligands that recognize selected cell membrane receptors, it is possible to design systems capable of specific tumor cell targeting and true intracellular delivery of both conventional and peptide-based anticancer drugs [ 150 , 151 , 152 ]. In this project by Edwards, the possibilities to use lipodisks for the co-delivery of chemotherapeutic drugs and membranolytic anticancer peptides will be investigated.…”

A Systematic Approach for Liposome and Lipodisk Preclinical Formulation Development by Microfluidic Technology

“…Several formulation approaches were adapted to improve the EE, including altering drug to lipid (D/L) ratio (23,32), leveraging remote loading (33,34), and increasing polyethylene glycol (PEG) ratios, which promotes the morphology change from liposomes to lipodisks. Lipodisks consist of a disk-like structure where the phospholipids form a flat lipid surface, and the PEG-lipids are located at the highly curved rim (35)(36)(37). Many published results suggest that lipodisks are promising nanocarriers, and the rich contents of PEG may promote improved EE (38)(39)(40)(41).…”