Polymeric glabrescione B nanocapsules for passive targeting of Hedgehog-dependent tumor therapy in vitro

  • Nanomedicine (Lond). 2017 Apr;12(7):711-728. doi: 10.2217/nnm-2016-0388.
Cinzia Ingallina  1  2 ,  Pedro M Costa  1 ,  Francesca Ghirga  3 ,  Rebecca Klippstein  1 ,  Julie T Wang  1 ,  Simone Berardozzi  2  3 ,  Naomi Hodgins  1 ,  Paola Infante  3 ,  Steven M Pollard  4 ,  Bruno Botta  2 ,  Khuloud T Al-Jamal  1
Affiliations
  • 1. Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, Franklin-Wilkins Building, London, SE1 9NH, UK.
  • 2. Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, Rome, Italy.
  • 3. Center for Life NanoScience@Sapienza, Istituto Italiano di Tecnologia, Rome, Italy.
  • 4. MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh bioQuarter, 5 Little France Drive, Edinburgh EH16 4UU, UK.
PMID: 28322108 DOI: 10.2217/nnm-2016-0388
Abstract

Aim: With the purpose of delivering high doses of glabrescione B (GlaB) to solid tumors after systemic administration, long-circulating GlaB-loaded oil-cored polymeric nanocapsules (NC-GlaB) were formulated.

Materials & methods: Synthesis of GlaB and its encapsulation in nanocapsules (NCs) was performed. Empty and GlaB-loaded NCs were assessed for their physico-chemical properties, in vitro cytotoxicity and in vivo biodistribution.

Results: GlaB was efficiently loaded into NCs (∽90%), which were small (∽160 nm), homogeneous and stable upon storage. Further, GlaB and NC-GlaB demonstrated specific activities against the Cancer Stem Cells. Preliminary studies in tumor-bearing mice supported the ability of NC to accumulate in pancreatic tumors.

Conclusion: This study provides early evidence that NC-GlaB has the potential to be utilized in a preclinical setting and justifies the need to perform therapeutic experiments in mice.

Keywords
Hedgehog (Hh) pathway; glabrescione B (GlaB); oil-cored polymeric nanocapsules.
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