HPMA copolymer–phospholipase C and dextrin–phospholipase A2 as model triggers for polymer enzyme liposome therapy (PELT)

Elaine L. Ferguson*, Anna Scomparin, Hanna Hailu, Ronit Satchi-Fainaro

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


‘Polymer Enzyme Liposome Therapy’ (PELT) is a two-step anticancer approach in which a liposomal drug and polymer-phospholipase conjugate are administered sequentially to target the tumour interstitium by the enhanced permeability and retention effect, and trigger rapid, local, drug release. To date, however, the concept has only been described theoretically. We synthesised two polymer conjugates of phospholipase C (PLC) and A2 (PLA2) and evaluated their ability to trigger anthracycline release from the clinically used liposomes, Caelyx® and DaunoXome®. N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymer–PLC and a dextrin-PLA2 were synthesised and their enzymatic activity characterised. Doxorubicin release from polyethyleneglycol-coated (PEGylated) Caelyx® was relatively slow (<20%, 60 min), whereas daunomycin was rapidly released from non-PEGylated DaunoXome® (∼87%) by both enzymes. Incubation with dextrin–PLA2 triggered significantly less daunomycin release than HPMA copolymer-PLC, but when dextrin-PLA2 was pre-incubated with α-amylase, the rate of daunomycin release increased. DaunoXome®’s diameter increased in the presence of PLA2, while Caelyx®’s diameter was unaffected by free or conjugated PLA2. Dextrin–PLA2 potentiated the cytotoxicity of DaunoXome® to MCF-7 cells to a greater extent than free PLA2, while combining dextrin–PLA2 with Caelyx® resulted in antagonism, even in the presence of α-amylase, presumably due to steric hindrance by PEG. Our findings suggest that in vivo studies to evaluate PELT combinations should be further evaluated.

Original languageEnglish
Pages (from-to)818-828
Number of pages11
JournalJournal of Drug Targeting
Issue number9-10
StatePublished - 26 Nov 2017


  • PELT
  • liposome
  • phospholipases
  • polymer therapeutics
  • polymer–protein conjugate


Dive into the research topics of 'HPMA copolymer–phospholipase C and dextrin–phospholipase A2 as model triggers for polymer enzyme liposome therapy (PELT)'. Together they form a unique fingerprint.

Cite this