Graphical Abstract

The Little Details

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Liposomes can carry a wide range of drugs, from small molecules like doxurubicin to macromolecules like siRNA. The drug payload can be adapted for future systems, but in our design we use a dummy fluorescent drug called TopFluor Cholesterol.


1,2-Distaeroyl-sn-glycero-3-phosphoethanolamine-Polyethylene Glycol (DSPE-PEG 2000) is an amphiphilic block copolymer that anchors into the hydrophobic tails of the liposome bilayer. The hydroxyl terminal group of PEG2000 is modified to attach to various ligands such as APOE or EGF. Modified DSPE-PEG linkers have shown to increase drug circulation time and increase delivery specificity.

Epidermal Growth Factor

EGFRs are overexpressed in around 50% of all glioblastoma cases. EGF binds to the EGFR and allows for the DDS to get taken in via receptor mediated endocytosis.

pH-Sensitive Hydrazone (HZ) Bond

The hydrazone bond hydrolyzes at acidic microenvironments (~pH 5.5-6.0) such as the endosomal compartments. Hydrolysis of the HZ bond will cleave APOE off, allowing for more specific EGF ligand uptake.


APOE is a lipoprotein that binds to the low-density-lipoprotein receptors (LDLRs) on the BBB. It transfers APOE to the brain side via receptor mediated transcytosis.

Liposome Capsule

The lipid bilayer is made up of a 1:2 ratio of 1,2-Distaeroyl-sn-glycero-3-phosphocholine (DSPC) & cholesterol. DSPC is a long chain saturated phospholipid, while cholesterol improves plasma stability and increase lipid density.

The Big Picture

Step-by-step process:

  1. Apolipoprotein-E (APOE) on the drug delivery system (DDS) binds to lipoprotein receptors (LDLRs)

  2. DDS gets taken up by the LDLR

  3. DDS passes through early endosomes (pH 6.5)

  4. DDS passes through late endosomes (pH 5.5) and the acid labile hydrazone (HZ) bond cleaves APOE off from DDS

  5. Epidermal growth facter (EGF) on the DDS binds to overexpressed EGF receptors (EGFRs) on the glioblastoma


Project Design