Journal
ACS NANO
Volume 6, Issue 8, Pages 6667-6674Publisher
AMER CHEMICAL SOC
DOI: 10.1021/nn3010476
Keywords
drug delivery; antibodies; cell targeting; layer-by-layer; click chemistry; internalization; nanoparticle
Categories
Funding
- Australian Research Council (ARC) under the Discovery Project [DP0877360]
- Future Fellowship [FT110100265]
- Federation Fellowship schemes [FF0776078]
- National Health and Medical Research Council (NHMRC) of Australia Program Grant [433607, 487992]
- Senior Research Fellowship
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The development of nanoengineered particles, such as polymersomes, liposomes, and polymer capsules, has the potential to offer significant advances in vaccine and cancer therapy. However, the effectiveness of these carriers has the potential to be greatly improved if they can be specifically delivered to target cells. We describe a general method for functionalizing nanoengineered polymer capsules with antibodies using click chemistry and investigate their interaction with cancer cells in vitro. The binding efficiency to cells was found to be dependent on both the capsule-to-cell ratio and the density of antibody on the capsule surface. In mixed cell populations, more than 90% of target cells bound capsules when the capsule-to-target cell ratio was 1:1. Strikingly, greater than 50% of target cells exhibited capsules on the cell surface even when the target cells were present as less than 0.1% of the total cell population. Imaging flow cytometry was used to quantify the internalization of the capsules, and the target cells were found to internalize capsules efficiently. However, the role of the antibody in this process was determined to enhance accumulation of capsules on the cell surface rather than promote endocytosis. This represents a significant finding, as this is the first study into the role antibodies play in internalization of such capsules. It also opens up the possibility of targeting these capsules to cancer cells using targeting molecules that do not trigger an endocytic pathway. We envisage that this approach will be generally applicable to the specific targeting of a variety of nanoengineered materials to cells.
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