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ACS Appl Mater Interfaces. 2020 Mar 17. doi: 10.1021/acsami.0c01786. [Epub ahead of print]

Engineered pH-Responsive Mesoporous Carbon Nanoparticles for Drug Delivery.

Author information

1
Department of Chemistry in Pharmaceutical Sciences, Faculty of Pharmacy, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Plaza Ramón y Cajal s/n, 28040 Madrid, Spain.
2
Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 28029 Madrid, Spain.
3
Julius Wolff Institute and Center for Musculoskeletal Surgery, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany.
4
Berlin-Brandenburg School for Regenerative Therapies, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany.
5
National Center for Scientific Research "Demokritos", Agia Paraskevi Attikis, 15341 Athens, Greece.
6
Department of Materials Science and Engineering, University of Ioannina, GR-45110 Ioannina, Greece.
7
Berlin Institute of Health Center for Regenerative Therapies, 13353 Berlin, Germany.

Abstract

In this work, two types of mesoporous carbon particles with different morphology, size, and pore structure have been functionalized with a self-immolative polymer sensitive to changes in pH and tested as drug nanocarriers. It is shown that their textural properties allow significantly higher loading capacity compared to typical mesoporous silica nanoparticles. In vial release experiments of a model Ru dye at pH 7.4 and 5 confirm the pH-responsiveness of the hybrid systems, showing that only small amounts of the cargo are released at physiological pH, whereas at slightly acidic pH (e.g., that of lysosomes), self-immolation takes place and a significant amount of the cargo is released. Cytotoxicity studies using human osteosarcoma cells show that the hybrid nanocarriers are not cytotoxic by themselves but induce significant cell growth inhibition when loaded with a chemotherapeutic drug such as doxorubicin. In preparation of an in vivo application, in vial responsiveness of the hybrid system to short-term pH-triggering is confirmed. The consecutive in vivo study shows no substantial cargo release over a period of 96 h under physiological pH conditions. Short-term exposure to acidic pH releases an experimental fluorescent cargo during and continuously after the triggering period over 72 h.

KEYWORDS:

controlled release; drug delivery; mesoporous carbons; pH-responsive; self-immolative coating

PMID:
32141284
DOI:
10.1021/acsami.0c01786

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