Targeted camptothecin delivery via silicon nanoparticles reduces breast cancer metastasis

Marietta Landgraf; Christoph A Lahr; Ishdeep Kaur; Abbas Shafiee; Alvaro Sanchez-Herrero; Phillip W Janowicz; Akhilandeshwari Ravichandran; Christopher B Howard; Anna Cifuentes-Rius; Jacqui A McGovern; Nicolas H Voelcker; Dietmar W Hutmacher

doi:10.1016/j.biomaterials.2020.119791

Targeted camptothecin delivery via silicon nanoparticles reduces breast cancer metastasis

Biomaterials. 2020 May:240:119791. doi: 10.1016/j.biomaterials.2020.119791. Epub 2020 Jan 17.

Affiliations

¹ Centre in Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia.
² Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.
³ Centre in Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia; UQ Diamantina Institute, Translational Research Institute, The University of Queensland, Brisbane, QLD, Australia.
⁴ The Centre for Advanced Imaging (CAI), The University of Queensland, Brisbane, QLD, 4072, Australia.
⁵ Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, Australia.
⁶ Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia. Electronic address: anna.cifuentesrius@monash.edu.
⁷ Centre in Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia. Electronic address: jacqui.mcgovern@qut.edu.au.
⁸ Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia; Commonwealth Scientific and Industrial Research Organization (CSIRO), Clayton, VIC, Australia; Department of Materials Science and Engineering, Monash University, Clayton, VIC, Australia; Melbourne Centre for Nanofabrication, Victorian Node of the Australian National Fabrication Facility, Clayton, VIC, Australia. Electronic address: nicolas.voelcker@monash.edu.
⁹ Centre in Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia. Electronic address: dietmar.hutmacher@qut.edu.au.

PMID: 32109589
DOI: 10.1016/j.biomaterials.2020.119791

Abstract

In advanced breast cancer (BCa) patients, not the primary tumor, but the development of distant metastases, which occur mainly in the organ bone, and their adverse health effects are responsible for high mortality. Targeted delivery of already known drugs which displayed potency, but rather unfavorable pharmacokinetic properties, might be a promising approach to overcome the current limitations of metastatic BCa therapy. Camptothecin (CPT) is a highly cytotoxic chemotherapeutic compound, yet poorly water-soluble and non-specific. Here, CPT was loaded into porous silicon nanoparticles (pSiNP) displaying the epidermal growth factor receptor (EGFR)-targeting antibody (Ab) cetuximab to generate a soluble and targeted nanoscale delivery vehicle for cancer treatment. After confirming the cytotoxic effect of targeted CPT-loaded pSiNP in vitro on MDA-MB-231BO cells, nanoparticles were studied in a humanized BCa bone metastasis mouse model. Humanized tissue-engineered bone constructs (hTEBCs) provided a humanized microenvironment for BCa bone metastases in female NOD-scid IL2Rg^null (NSG) mice. Actively targeted CPT-loaded pSiNP led to a reduction of orthotopic primary tumor growth, increased survival rate and significant decrease in hTEBC and murine lung, liver and bone metastases. This study demonstrates that targeted delivery via pSiNP is an effective approach to employ CPT and other potent anti-cancer compounds with poor pharmacokinetic profiles in cancer therapy.

Keywords: Bone metastases; Chemotherapy; Drug delivery; Humanized animal model; Porous silicon; Triple-negative breast cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Breast Neoplasms* / drug therapy
Camptothecin
Cell Line, Tumor
Female
Humans
Mice
Mice, Inbred NOD
Nanoparticles*
Silicon
Tumor Microenvironment

Substances

Camptothecin
Silicon