Gelatin-albumin Hybrid Nanoparticles As Matrix metalloproteinases-degradable Delivery Systems for Breast Cancer Therapy

Abstract

Aim: To develop matrix metalloproteinase-responsive gelatin-albumin hybrid nanoparticles encapsulating a selective tropomyosin receptor kinase A (TrkA) inhibitor GNF-5837 (Gel-Alb-GNF HNPs) and to demonstrate their anticancer effects in breast cancer. Methods: Gel-Alb-GNF HNPs were prepared using a pH-controlled complexation process from cationic gelatin, dextran sulfate and albumin-bound GNF-5837. The anticancer activities of Gel-Alb-GNF HNPs were tested in a panel of subtype-specific breast cancer cell lines. Results: Gel-Alb-GNF HNPs (∼130 nm) displayed excellent stability and matrix metalloproteinase-triggered drug release. Compared with GNF-5837 alone, Gel-Alb-GNF HNPs not only significantly enhanced the antiproliferative and anti-invasive effects but also restored the apoptosis of cancer cells. Conclusion: Gel-Alb-GNF HNPs may be adaptable for stand-alone therapies or used in combination with traditional chemotherapies for breast cancer treatment.

Keywords:

• breast cancer
• hybrid nanoparticles
• matrix metalloproteinase
• TrkA inhibitor

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at:www.tandfonline.com/doi/full/10.2217/epi-2016-0184

Acknowledgements

The Electron Microscope and X-Ray Unit (EMX) of the University of Newcastle is acknowledged for SEM images.

Financial & competing interests disclosure

This work was supported by the School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Australia. VH Shargh received the University of Newcastle International Postgraduate Research Scholarship (UNIPRS) and the University of Newcastle Postgraduate Research Scholarship Central (UNRSC50:50). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.