Figueroa, Sara Maslanka and Veser, Anika and Abstiens, Kathrin and Fleischmann, Daniel and Beck, Sebastian and Goepferich, Achim (2019) Influenza A virus mimetic nanoparticles trigger selective cell uptake. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 116 (20). pp. 9831-9836. ISSN 0027-8424,
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Poor target cell specificity is currently a major shortcoming of nanoparticles (NPs) used for biomedical applications. It causes significant material loss to off-target sites and poor availability at the intended delivery site. To overcome this limitation, we designed particles that identify cells in a virus-like manner. As a blueprint, we chose a mechanism typical of influenza A virus particles in which ectoenzymatic hemagglutinin activation by target cells is a mandatory prerequisite for binding to a secondary target structure that finally confirms cell identity and allows for uptake of the virus. We developed NPs that probe mesangial cells for the presence of angiotensin-converting enzyme on their surface using angiotensin I (Ang-I) as a proligand. This initial interaction enzymatically transforms Ang-I to a secondary ligand angiotensin II (Ang-II) that has the potential to bind in a second stage to Ang-II type-1 receptor (AT1R). The presence of the receptor confirms the target cell identity and triggers NP uptake via endocytosis. Our virus-mimetic NPs showed outstanding target-cell affinity with picomolar avidities and were able to selectively identify these cells in the presence of 90% offtarget cells that carried only the AT1R. Our results demonstrate that the design of virus-mimetic cell interactive NPs is a valuable strategy to enhance NP specificity for therapeutic and diagnostic applications. Our set of primary and secondary targets is particularly suited for the identification of mesangial cells that play a pivotal role in diabetic nephropathy, one of the leading causes of renal failure, for which currently no treatment exists.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ENZYME-RESPONSIVE NANOPARTICLES; ANGIOTENSIN-II GENERATION; DELIVERY-SYSTEMS; ACE-INHIBITORS; BINDING; MULTIVALENCY; ACCUMULATION; PHARMACOLOGY; AFFINITY; HEART; virus-mimetic nanoparticles; influenza A; heteromultivalent; target specific; enzyme responsive |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Technology (Prof. Göpferich) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Apr 2020 09:47 |
| Last Modified: | 08 Apr 2020 09:47 |
| URI: | https://pred.uni-regensburg.de/id/eprint/27014 |
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