Danzi Song, ,* Jiwei Cui, ,§ Yi Ju, Huanli Sun, ,^ Kristofer J. Thurecht, and Frank Caruso


ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and the Department of Chemical Engineering, School of Chemical and Biomedical Engineering, The University of Melbourne, Parkville, Victoria 3010, Australia
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and Australian Institute for Bioengineering and Nanotechnology, University of Queensland, St Lucia, Australia.
§Key Laboratory of Colloid and Interface Chemistry of Ministry of Education, and the School of Chemistry and Chemical Engineering, Shandong University, Jinan, Shandong 250100, China
^Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China


Drug carriers that have high targeting ability to cancer cells are often required in drug development. It is crucial to understand how the drug carrier properties can be tailored to avoid immune recognition and improve targeted cell association. Interactions of spherical polymeric capsules with cells have been studied extensively, however the effect of carrier shape and their potential to enhance systemic targeting have yet to be fully elucidated. Herein, we report the preparation of rod-shaped poly(ethylene glycol) (PEG) capsules with tunable aspect ratios (ARs) of 1, 8 and 20 via the fabrication method, termed continuous assembly of polymers. Bi-specific antibodies (BsAbs) which have dual specificities to PEG and epidermal growth factor receptor (EGFR) were used to facilitate the PEG capsule targeting. The cell-targeting of these capsules with varying shapes was studied under both static and dynamic flow conditions. EGFR positive human breast cancer cell line MDA-MB-468, EGFR negative Chinese hamster ovary cell line CHO-K1 and murine macrophage cell line RAW264.7 were used to study the targeting specificity. It was found that these BsAb-labeled capsules showed high positive cell targeting while maintaining negligible negative association. All of the BsAb-labeled PEG capsules regardless of shape could achieve up to 98% of targeting after 5 hours of incubation. The cellular internalization for capsules with aspect ratio 8 and 20 was ~10% higher than their spherical counterparts with the same surface area under dynamic flow conditions. The dynamic incubation enhanced the cellular uptake for all types of capsules but more significantly for the smaller ones (500 nm and AR8). This study will enable a rational selection of capsule design for future development.