Cellular Targeting of Bispecific Antibody-Functionalized Poly(ethylene glycol) Capsules: Do Shape and Size Matter?

Danzi Song; Jiwei Cui; Yi Ju; Matthew Faria; Huanli Sun; Christopher B Howard; Kristofer J Thurecht; Frank Caruso

doi:10.1021/acsami.9b10304

Cellular Targeting of Bispecific Antibody-Functionalized Poly(ethylene glycol) Capsules: Do Shape and Size Matter?

ACS Appl Mater Interfaces. 2019 Aug 14;11(32):28720-28731. doi: 10.1021/acsami.9b10304. Epub 2019 Aug 1.

Authors

Danzi Song¹, Jiwei Cui^{1

2}, Yi Ju¹, Matthew Faria¹, Huanli Sun¹, Christopher B Howard³, Kristofer J Thurecht³, Frank Caruso¹

Affiliations

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 ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Centre for Advanced Imaging and Australian Institute for Bioengineering and Nanotechnology , The University of Queensland , St. Lucia , Queensland 4072 , Australia.

PMID: 31369234
DOI: 10.1021/acsami.9b10304

Abstract

In the present study, a capsule system that consists of a stealth carrier based on poly(ethylene glycol) (PEG) and functionalized with bispecific antibodies (BsAbs) is introduced to examine the influence of the capsule shape and size on cellular targeting. Hollow spherical and rod-shaped PEG capsules with tunable aspect ratios (ARs) of 1, 7, and 18 were synthesized and subsequently functionalized with BsAbs that exhibit dual specificities to PEG and epidermal growth factor receptor (EGFR). Dosimetry (variation between the concentrations of capsules present and capsules that reach the cell surface) was controlled through "dynamic" incubation (i.e., continuously mixing the incubation medium). The results obtained were compared with those obtained from the "static" incubation experiments. Regardless of the incubation method and the capsule shape and size studied, BsAb-functionalized PEG capsules showed >90% specific cellular association to EGFR-positive human breast cancer cells MDA-MB-468 and negligible association with both control cell lines (EGFR negative Chinese hamster ovary cells CHO-K1 and murine macrophages RAW 264.7) after incubation for 5 h. When dosimetry was controlled and the dose concentration was normalized to the capsule surface area, the size or shape had a minimal influence on the cell association behavior of the capsules. However, different cellular internalization behaviors were observed, and the capsules with ARs 7 and 18 were, respectively, the least and most optimal shape for achieving high cell internalization under both dynamic and static conditions. Dynamic incubation showed a greater impact on the internalization of rod-shaped capsules (∼58-67% change) than on the spherical capsules (∼24-29% change). The BsAb-functionalized PEG capsules reported provide a versatile particle platform for the evaluation and comparison of cellular targeting performance of capsules with different sizes and shapes in vitro.

Keywords: bispecific antibody; cell targeting; dosimetry; poly(ethylene glycol); polymer capsules.

MeSH terms

Animals
Antibodies, Bispecific* / chemistry
Antibodies, Bispecific* / pharmacology
Antineoplastic Agents, Immunological* / chemistry
Antineoplastic Agents, Immunological* / pharmacology
CHO Cells
Capsules
Cricetulus
Drug Delivery Systems*
Humans
Mice
Polyethylene Glycols* / chemistry
Polyethylene Glycols* / pharmacology
RAW 264.7 Cells

Substances

Antibodies, Bispecific
Antineoplastic Agents, Immunological
Capsules
Polyethylene Glycols