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

Author:
Song, Danzi, Cui, Jiwei, Ju, Yi, Faria, Matthew, Sun, Huanli, Howard, Christopher B., Thurecht, Kristofer J., Caruso, Frank
Source:
ACS applied materials & interfaces 2019 v.11 no.32 pp. 28720-28731
ISSN:
1944-8252
Subject:
Chinese hamsters, animal ovaries, antibodies, breast neoplasms, cell lines, dosimetry, epidermal growth factor receptors, humans, macrophages, mice, mixing, neoplasm cells, polyethylene glycol, surface area
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.
Agid:
6564418