Tuneable peptide cross-linked nanogels for enzyme-triggered protein delivery
In: 8907 ; 8894, 2020
Online
academicJournal
Zugriff:
Many diseases are associated with the dysregulated activity of enzymes, such as matrix metalloproteinases (MMPs). This dysregulation can be leveraged in drug delivery to achieve disease- or site-specific cargo release. Self-assembled polymeric nanoparticles are versatile drug carrier materials due to the accessible diversity of polymer chemistry. However, efficient loading of sensitive cargo, such as proteins, and introducing functional enzyme-responsive behaviour remain challenging. Herein, peptide-crosslinked, temperature-sensitive nanogels for protein delivery were designed to respond to MMP-7, which is overexpressed in many pathologies including cancer and inflammatory diseases. The incorporation of N-cyclopropylacrylamide (NCPAM) into N-isopropylacrylamide (NIPAM)-based copolymers enabled us to tune the polymer lower critical solution temperature from 33 to 44 1C, allowing the encapsulation of protein cargo and nanogel-crosslinking at slightly elevated temperatures. This approach resulted in nanogels that were held together by MMP-sensitive peptides for enzymespecific protein delivery. We employed a combination of cryogenic transmission electron microscopy (cryo-TEM), dynamic light scattering (DLS), small angle neutron scattering (SANS), and fluorescence correlation spectroscopy (FCS) to precisely decipher the morphology, self-assembly mechanism, enzyme-responsiveness, and model protein loading/release properties of our nanogel platform. Simple variation of the peptide linker sequence and combining multiple different crosslinkers will enable us to adjust our platform to target specific diseases in the future.
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Tuneable peptide cross-linked nanogels for enzyme-triggered protein delivery
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Autor/in / Beteiligte Person: | Massi, L ; Najer, A ; Chapman, R ; Spicer, C ; Nele, V ; Che, J ; Booth, MA ; Doutch, JJ ; Stevens, M ; British Heart Foundation ; Medical Research Council (MRC) ; Engineering & Physical Science Research Council (EPSRC) ; Trust, Wellcome ; Commission of the European Communities |
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Zeitschrift: | 8907 ; 8894, 2020 |
Veröffentlichung: | Royal Society of Chemistry, 2020 |
Medientyp: | academicJournal |
ISSN: | 2050-750X (print) |
DOI: | 10.1039/D0TB01546F |
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