Dual-responsive nanoparticles release cargo upon exposure to matrix metalloproteinase and reactive oxygen species

Daniel, Kevin B.; Callmann, Cassandra E.; Gianneschi, Nathan C.; Cohen, Seth M.

doi:10.1039/c5cc09164k

Cited by 27 publications

(19 citation statements)

References 32 publications

(50 reference statements)

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“…It can be useful as a trigger for cargo release, similar to already demonstrated amphiphilic polymerbased nanoparticle systems with drug release enzymatic response. 54 We further demonstrated that minute alteration in the disordered peptide sequence and dendrimer architecture could significantly impact the nanoscopic and macroscopic lengthscales. This platform also enables in-situ modifications of the IDPs and the study of the mutual interaction between IDPs.…”

Section: Resultsmentioning

confidence: 79%

Order from Disorder with Intrinsically Disordered Peptide Amphiphiles

Jacoby¹,

Segal²,

Ehm³

et al. 2021

Preprint

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Amphiphilic molecules and their self-assembled structures have long been the target of extensive research due to their potential applications in fields ranging from materials design to biomedical and cosmetic applications. Increasing demands for functional complexity have been met with challenges in biochemical engineering, driving researchers to innovate in the design of new amphiphiles. An emerging class of molecules, namely, peptide amphiphiles, combines key advantages and circumvents some of the disadvantages of conventional phospholipids and block-copolymers. Herein, we present new peptide amphiphiles comprised of an intrinsically disordered peptide conjugated to two variants of hydrophobic dendritic domains. These molecules termed intrinsically disordered peptide amphiphiles (IDPA), exhibit a sharp pH-induced micellar phase-transition from low-dispersity spheres to extremely elongated worm-like micelles. We present an experimental characterization of the transition and propose a theoretical model to describe the pH-response. We also present the potential of the shape transition to serve as a mechanism for the design of a cargo hold-and-release application. Such amphiphilic systems demonstrate the power of tailoring the interactions between disordered peptides for various stimuli-responsive biomedical applications.

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Section: Resultsmentioning

confidence: 79%

Order from Disorder with Intrinsically Disordered Peptide Amphiphiles

Jacoby¹,

Segal²,

Ehm³

et al. 2021

Preprint

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“…Boronate ester–based ROS sensitivity was also exploited by Daniel et al., where they designed a block copolymer prodrug system that could self‐assemble in aqueous conditions to form particles. The prodrug consisted of an inhibitor for MMPs, which are commonly found in areas of increased ROS concentration, tethered to the polymer backbone through an aryl boronic ester moiety.…”

Section: Methods Of Stimuli‐responsive Drug Deliverymentioning

confidence: 99%

Stimuli‐Responsive Prodrug Chemistries for Drug Delivery

Taresco

Alexander

Singh

et al. 2018

Advanced Therapeutics

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Research into advanced therapeutic materials is of growing importance worldwide, particularly in the disease areas of infection, neurodegeneration, and oncology. Advances have been made in treating these diverse pathologies but there still remain many challenging areas. Amongst the most difficult are those involving highly potent and/or cytotoxic agents which present the inherent problem of adverse off-target effects. Of key importance is to widen the therapeutic window for such agents by reducing access to non-diseased cells and enhancing release at targeted sites. Spatiotemporal controlled release can be achieved by exploiting physical, chemical, or biological stimuli present at the specific diseased area. A crucial strategy involves drug-carrier linkages able to respond to physiological or biochemical stimuli present in the disease region, and there is now significant literature on (polymeric) prodrugs based on the drug + carrier + cleavable linker philosophy, predominantly for cancer applications. The authors therefore focuse this mini-review primarily on single/multistimuli-responsive prodrugs for cancer therapies, covering prominent examples of prodrug chemistries used to endow polymers with controlled and site-specific drug delivery properties. Additionally, the possibilities for exploiting similar approaches to disease-associated stimuli present in bacterial and viral infections, inflammatory and immune diseases, and in degenerative disorders are emphasized.

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“…Other systems are responsive to a combination of different stimuli. The association of MMP- and reactive oxygen species (ROS)-responsiveness enabled Daniel et al [ 215 ] to use amphiphilic polymer NPs in inflammatory diseases, such as myocardial infarction, arthritis, ischemia and atherosclerosis, where both are upregulated. With this design approach they achieved specific in vivo targeting of ischemic skeletal muscle [ 216 ], avoiding off-target accumulation in healthy muscle and regulating macrophage internalization [ 217 ].…”

Section: Stimuli Responsivenessmentioning

confidence: 99%

Biomedical nanoparticle design: What we can learn from viruses

Figueroa

Fleischmann

Goepferich

2021

Journal of Controlled Release

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Viruses are nanomaterials with a number of properties that surpass those of many synthetic nanoparticles (NPs) for biomedical applications. They possess a rigorously ordered structure, come in a variety of shapes, and present unique surface elements, such as spikes. These attributes facilitate propitious biodistribution, the crossing of complex biological barriers and a minutely coordinated interaction with cells. Due to the orchestrated sequence of interactions of their stringently arranged particle corona with cellular surface receptors they effectively identify and infect their host cells with utmost specificity, while evading the immune system at the same time. Furthermore, their efficacy is enhanced by their response to stimuli and the ability to spread from cell to cell. Over the years, great efforts have been made to mimic distinct viral traits to improve biomedical nanomaterial performance. However, a closer look at the literature reveals that no comprehensive evaluation of the benefit of virus-mimetic material design on the targeting efficiency of nanomaterials exists. In this review we, therefore, elucidate the impact that viral properties had on fundamental advances in outfitting nanomaterials with the ability to interact specifically with their target cells. We give a comprehensive overview of the diverse design strategies and identify critical steps on the way to reducing them to practice. More so, we discuss the advantages and future perspectives of a virus-mimetic nanomaterial design and try to elucidate if viral mimicry holds the key for better NP targeting.

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Dual-responsive nanoparticles release cargo upon exposure to matrix metalloproteinase and reactive oxygen species

Cited by 27 publications

References 32 publications

Order from Disorder with Intrinsically Disordered Peptide Amphiphiles

Order from Disorder with Intrinsically Disordered Peptide Amphiphiles

Stimuli‐Responsive Prodrug Chemistries for Drug Delivery

Biomedical nanoparticle design: What we can learn from viruses

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