PCSK9 conjugated liposomes for targeted delivery of paclitaxel to the cancer cell: A proof-of-concept study

Nitin Bharat Charbe, Carlos F. Lagos, Cristian Andrés Vilos Ortiz, Murtaza Tambuwala, Sushesh Srivatsa Palakurthi, Flavia C. Zacconi

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Ligand-based targeting of the receptors that are overexpressed explicitly on cancer cells represents an effective drug delivery approach to enhance the chemotherapeutic efficacy. Proprotein convertase subtilisin/kexin type 9 (PCSK9) which is a serine protease enzyme primarily produced by the liver cells, can potentially be used as a targeting ligand. PCSK9 binds to the LDL-r on hepatocytes' surface, leading to endocytosis and endosomal degradation. High LDL-r expression, which is believed to meet the higher demand of the cholesterol and phospholipids to build proliferating cancer cell membrane, ensures selective uptake of the PCSK9 conjugated liposomes. In the present work, the PCSK9 conjugated liposomal system was developed to deliver paclitaxel (PTX) to cancer cells. The protein was conjugated by EDC and NHS in a two-step coupling reaction to the liposomes containing COOH-PEG 2000-COOH lipid. Conjugation was confirmed by NMR, and liposomes were further characterized by SEM and zeta sizer. PCSK9-conjugated liposomes showed high encapsulation efficiency of 69.1% with a diameter of 90.0 ± 4.9 nm. Long-term stability (30 days) study (Zeta potential: −9.88) confirmed excellent constancy and significant drug retention (58.2%). Invitro cytotoxicity and targeting efficiency was explored using MTS assay in human embryonic kidney cells (HEK293), liver hepatocellular cells (HEPG2), and a human colon cancer cell line (HCT116) for 24 h. PCSK9 conjugated liposomes exhibited significantly higher growth inhibition than the unconjugated (control) liposomes in HCT116 cell line (p < 0.001). The novel PCSK9 conjugated liposomes presented potent and precise in vitro anticancer activity and, therefore, are suggested for the first time as a promising targeted delivery system for cancer treatment.

Original languageEnglish
Article number113428
Pages (from-to)1-13
Number of pages13
JournalBiomedicine and Pharmacotherapy
Early online date15 Jul 2022
Publication statusPublished (in print/issue) - 30 Sept 2022

Bibliographical note

Funding Information:
Nitin Bharat Charbe is the recipient of ANID/CONICYT POSTDOCTORADO Fellowship (PROYECTO N° 3180250).

Publisher Copyright:
© 2022 The Authors


  • Cancer
  • PCSK9
  • Targeted drug delivery system
  • Lipsome
  • Low-density lipoprotein receptor
  • Nanomedicine
  • Paclitaxel - pharmacology
  • Humans
  • Liposome
  • Receptors, LDL - metabolism
  • Proprotein Convertase 9 - metabolism
  • Neoplasms - drug therapy
  • Proprotein Convertases - chemistry - metabolism
  • HEK293 Cells
  • Ligands
  • Liposomes


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