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Adv Healthc Mater. 2019 Mar 14:e1801607. doi: 10.1002/adhm.201801607. [Epub ahead of print]

Modulating Targeting of Poly(ethylene glycol) Particles to Tumor Cells Using Bispecific Antibodies.

Author information

1
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and the Department of Chemical Engineering, The University of Melbourne, Parkville, Victoria, 3010, Australia.
2
Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education, School of Chemistry and Chemical Engineering, Shandong University, Jinan, Shandong, 250100, China.
3
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia, Queensland, 4072, Australia.
4
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and the Centre for Advanced Imaging, The University of Queensland, St. Lucia, Queensland, 4072, Australia.
5
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and the Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville, Victoria, 3010, Australia.
6
ARC Training Centre for Biopharmaceutical Innovation, The University of Queensland, St. Lucia, Queensland, 4072, Australia.
7
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria, 3052, Australia.
8
Materials Characterisation and Fabrication Platform, The University of Melbourne, Parkville, Victoria, 3010, Australia.
9
School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, 3010, Australia.

Abstract

Low-fouling or "stealth" particles composed of poly(ethylene glycol) (PEG) display a striking ability to evade phagocytic cell uptake. However, functionalizing them for specific targeting is challenging. To address this challenge, stealth PEG particles prepared by a mesoporous silica templating method are functionalized with bispecific antibodies (BsAbs) to obtain PEG-BsAb particles via a one-step binding strategy for cell and tumor targeting. The dual specificity of the BsAbs-one arm binds to the PEG particles while the other targets a cell antigen (epidermal growth factor receptor, EGFR)-is exploited to modulate the number of targeting ligands per particle. Increasing the BsAb incubation concentration increases the amount of BsAb tethered to the PEG particles and enhances targeting and internalization into breast cancer cells overexpressing EGFR. The degree of BsAb functionalization does not significantly reduce the stealth properties of the PEG particles ex vivo, as assessed by their interactions with primary human blood granulocytes and monocytes. Although increasing the BsAb amount on PEG particles does not lead to the expected improvement in tumor accumulation in vivo, BsAb functionalization facilitates tumor cell uptake of PEG particles. This work highlights strategies to balance evading nonspecific clearance pathways, while improving tumor targeting and accumulation.

KEYWORDS:

PEG particles; biodistribution; bispecific antibodies; cell targeting; mesoporous silica particles

PMID:
30868751
DOI:
10.1002/adhm.201801607

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