An enzyme-responsive controlled release system based on a dual-functional peptide

Li, X.; Bürger, Stephan; O’Connor, Andrea J.; Ong, Lydia; Karas, John A.; Gras, Sally L.

doi:10.1039/c5cc10480g

Cited by 17 publications

(8 citation statements)

References 32 publications

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“…By using HA‐MA with different DM, the crosslinked films showed different final stiffness as 190.8 ± 59.4 and 345.7 ± 56.1 kPa for 20% and 57%, respectively (Figure S3, Supporting Information). To test stiffness adaptivity of MMP(S)x‐CL film in response to MMPs, collagenase was employed to simulate enzyme environment . One can observe that, after the treatment of collagenase solution, the stiffness of MMP(S)x‐CL significantly decreased to 55.0 ± 13.4 kPa, the stiffness level of original uncrosslinked film; meanwhile MMP(IS)x‐CL had barely changed its stiffness showing 589.8 ± 191.4 kPa.…”

Section: Resultsmentioning

confidence: 91%

Mechanical Adaptability of the MMP‐Responsive Film Improves the Functionality of Endothelial Cell Monolayer

Chang

et al. 2017

Adv Healthcare Materials

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Extracellular matrix and cells are inherent in coordinating and adapting to each other during all physiological and pathological processes. Synthetic materials, however, show rarely reciprocal and spatiotemporal responses to cells, and lacking self-adapting properties as well. Here, a mechanical adaptability based on the matrix metalloproteinase (MMPs) sensitive polyelectrolyte film is reported. Poly-lysine (PLL) and methacrylated hyaluronic acid (HA-MA) nanolayers are employed to build the thin film through the layer-by-layer assembly, and it is further crosslinked using MMP sensitive peptides, which endows the films with changeable mechanical properties in response to MMPs. It is demonstrated that stiffness of the (PLL/HA-MA) films increases with the crosslinking, and then decreases in response to a treatment of enzyme. Consequently, the crosslinked (PLL/HA-MA) films reveal effective growth of endothelial cells (ECs), leading to fast formation of EC monolayer. Importantly, significantly improved endothelial function of the EC monolayer, which is characterized by integrity, biomolecules release, expression of function related gene, and antithrombotic properties, is achieved along with the decrosslinking of the film because of EC-secreted MMPs. These results suggest that mechanical adaptability of substrate in Young's modulus plays a significant role in endothelial progression, which shows great application potential in tissue engineering, regenerative medicine, and organ-on-a-chip.

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Section: Resultsmentioning

confidence: 91%

Mechanical Adaptability of the MMP‐Responsive Film Improves the Functionality of Endothelial Cell Monolayer

Chang

et al. 2017

Adv Healthcare Materials

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“…[26] Once exposed to the enzyme, enzyme-responsive self-assembled NPs incorporated with ester bonds and peptide segments as the substrate for enzyme reaction will release drugs at target sites owing to the fracture of ester bonds or peptide segments. [27,28,29]…”

Section: Enzyme-responsive Self-assembled Npsmentioning

confidence: 99%

“…Considering the variable types and levels of enzymes at the targeted site, accurate test results to design related enzyme-responsive DDSs should be obtained. [27][28][29] In recent years, redox-responsive self-assembled NPs have attracted great attention due to their efficient release effect and simple preparation process, which is expected to stand out among many stimuli-responsive self-assembled NPs.…”

Section: Multistimuli-responsive Self-assembled Npsmentioning

confidence: 99%

Redox‐Responsive Self‐Assembled Nanoparticles for Cancer Therapy

Zhang

Liu

et al. 2020

Adv Healthcare Materials

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Chemotherapy, combined with other treatments, is widely applied in the clinical treatment of cancer. However, deficiencies inherited from the traditional route of administration limit its successful application. With the development of nanotechnology, a series of smart nanodelivery systems have been developed to utilize the unique tumor environment (pH changes, different enzymes, and redox potential gradients) and exogenous stimuli (thermal changes, magnetic fields, and light) to improve the curative effect of anticancer drugs. In this review, endogenous and exogenous stimuli are briefly introduced. Among these stimuli, various redox-sensitive linkages are primarily described in detail, and their application with self-assembled nanoparticles is recounted. Finally, the application of redox-responsive self-assembled nanoparticles in cancer therapy is summarized.

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“…It has been reported that type I collagenase is able to depredate the MMP-sensitive peptide but not for the MMP-insensitive sequence used in this study; thus, using type I collagenase is a valid method to mimic enzyme cut and evaluate the MMP sensitivity of the same peptide sequence. 28,29 As shown in Figure 3, when prepared MNG bulk films with 7.5 μg of DNA incorporated were incubated with collagenase, only about 0.34 μg of DNA was released within the first 3 days. In contrast, the release rate of DNA from MDG was significantly higher than MNG, with more than 1 μg DNA release within the first 3 days, and the DNA release continued to increase as the incubation prolonged, demonstrating the stimuli-responsive degradation and DNA release behavior of MDG.…”

Section: ■ Resultsmentioning

confidence: 99%

Surface-Mediated Stimuli-Responsive Gene Delivery Based on Breath Figure Film Combined with Matrix Metalloproteinase-Sensitive Hydrogel

Zhang

Huang

Wang

et al. 2019

ACS Biomater. Sci. Eng.

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Surface-mediated gene delivery appears to be potential gene delivery modes for various applications. Still, controlled and smart delivery manners are required especially considering the need for gene therapy to deliver gene with selectivity. A surface that can effectively payload DNA, promote cell adhesion, and stimuli response is an important prerequisite. Here, we report a matrix metalloproteinase (MMP)-responsive surface-mediated gene delivery system by combining MMP-degradable hydrogel with a breath figure (BF) porous film. The MMP-degradable hydrogel containing plasmid DNA was loaded into the surface pores of the BF film as DNA reservoirs. The upper surface without hydrogel on the BF film served as footholds of integrin adhesions. MMP is one of the important endogenous signals in tumor-related pathologic changes, and MMP expressions in cancer cells are significantly higher than those in normal cells. Consequently, our surface-mediated gene delivery locally and rapidly released the payload DNA in response to cancer cells and transfected them. This work highlights the importance of the combination of stimuli-response and surface-mediated gene delivery to functional materials, showing good potential applications in the field of gene therapy.

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An enzyme-responsive controlled release system based on a dual-functional peptide

Cited by 17 publications

References 32 publications

Mechanical Adaptability of the MMP‐Responsive Film Improves the Functionality of Endothelial Cell Monolayer

Mechanical Adaptability of the MMP‐Responsive Film Improves the Functionality of Endothelial Cell Monolayer

Redox‐Responsive Self‐Assembled Nanoparticles for Cancer Therapy

Surface-Mediated Stimuli-Responsive Gene Delivery Based on Breath Figure Film Combined with Matrix Metalloproteinase-Sensitive Hydrogel

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