Journal
THERANOSTICS
Volume 10, Issue 1, Pages 109-122Publisher
IVYSPRING INT PUBL
DOI: 10.7150/thno.38388
Keywords
Titania nanotubes; pH-Responsive molecular gate; On-demand delivery; Bactericidal activity; Peptides
Categories
Funding
- National Key R&D Program of China [2018YFC 1105402, 2017YFC1104402, 2018YFC0311103]
- National Nature Science Foundation of China [U1801252, 31771027, 51603074]
- Science and Technology Program of Guangzhou [201804020060]
- Pearl River Nova Program of Guangzhou [201806010156]
- China Postdoctoral Science Foundation [2019M652907]
- Outstanding Scholar Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory [2018GZR110102001]
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Background: Localized delivery of antimicrobial agents such as antimicrobial peptides (AMPs) by a biomaterial should be on-demand. Namely, AMPs should be latent and biocompatible in the absence of bacterial infection, but released in an amount enough to kill bacteria immediately in response to bacterial infection. Methods: To achieve the unmet goal of such on-demand delivery, here we turned a titanium implant with titania nanotubes (Ti-NTs) into a Pandora's box. The box was loaded with AMPs (HHC36 peptides, with a sequence of KRWWKWWRR) inside the nanotubes and closed (surface-modified) with a pH-responsive molecular gate, poly(methacrylic acid) (PMAA), which swelled under normal physiological conditions (pH 7.4) but collapsed under bacterial infection (pH <= 6.0). Thus, the PMAA-gated Ti-NTs behaved just like a Pandora's box. The box retarded the burst release of AMPs under physiological conditions because the gate swelled to block the nanotubes opening. However, it was opened to release AMPs to kill bacteria immediately when bacterial infection occurred to lowering the pH (and thus made the gate collapse). Results: We demonstrated such smart excellent bactericidal activity against a panel of four clinically important bacteria, including Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus. In addition, this box was biocompatible and could promote the osteogenic differentiation of human mesenchymal stem cells. Both in vitro and in vivo studies confirmed the smart on-demand bactericidal activity of the Pandora's box. The molecularly gated Pandora's box design represents a new strategy in smart drug delivery.
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