Release of Anti-inflammatory Peptides from Thermosensitive Nanoparticles with Degradable Cross-Links Suppresses Pro-inflammatory Cytokine Production

Poh, Scott; Lin, Ji; Panitch, Alyssa

doi:10.1021/bm501849p

Cited by 34 publications

(40 citation statements)

References 43 publications

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“…Additionally the attached SILY, combined with the electrostatic attraction between the KAFAK and the particle, could hinder the release of any KAFAK that was successfully loaded into the core, resulting in the incomplete peptide release that was observed with these particles. Work has been done, in our lab and others, on the synthesis of degradable poly(NIPAM) nanoparticles (55)(56)(57)(58)(59)(60), and it is likely that the use of a similar system in these particles would result in a more complete peptide release profile over a longer time period.…”

Section: Discussionmentioning

confidence: 99%

Prevention of Collagen-Induced Platelet Binding and Activation by Thermosensitive Nanoparticles

McMasters

Panitch

2015

AAPS J

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ABSTRACT. Peripheral artery disease is an atherosclerotic occlusion in the peripheral vasculature that is typically treated via percutaneous transluminal angioplasty. Unfortunately, deployment of the angioplasty balloon damages the endothelial layer, exposing the underlying collagen and allowing for the binding and activation of circulating platelets, which initiate an inflammatory cascade leading to eventual restenosis. Here, we report on the development of poly(NIPAm-MBA-AMPS-AAc) nanoparticles that have a collagen I-binding peptide crosslinked to their surface allowing them to bind to exposed collagen. Once bound, these particles mask the exposed collagen from circulating platelets, effectively reducing collagen-mediated platelet activation. Using collagen I-coated plates, we demonstrate that these particles are able to bind to collagen at concentrations above 0.5 mg/mL. Once bound, these particles inhibit collagen-mediated platelet activation by over 60%. Using light scattering and zeta potential measurements, we investigated the potential of the nanoparticles as a drug delivery platform. We have verified that the collagen-binding nanoparticles retain the temperature sensitivity common to poly(NIPAm)-based nanoparticles while remaining colloidally stable in aqueous environments. We also demonstrate that they are able to passively load and release anti-inflammatory cell penetrating peptides. Combined, we have developed a collagen-binding nanoparticle that has dual therapy potential, preventing collagen-mediated platelet activation while delivering water-soluble therapeutics directly to the damaged area.

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Section: Discussionmentioning

confidence: 99%

Prevention of Collagen-Induced Platelet Binding and Activation by Thermosensitive Nanoparticles

McMasters

Panitch

2015

AAPS J

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“…As described previously, in aqueous solutions pNIPAM nanoparticles with 5% AMPS co-monomer remain spherical, well dispersed, and capable of delivering therapeutic peptides (14, 16). KAFAK-loaded pNIPAM nanoparticles with N,O-dimethacryloyl hydroxylamine (DMHA) crosslinks were reported to impart anti-inflammatory activity in cartilage explants and to penetrate deeply into aggrecan-depleted cartilage (15).…”

Section: Discussionmentioning

confidence: 64%

“…Nanoparticle and peptide synthesis were performed and characterized as previously reported with no modifications (16). Details of experimental methods are provided in supplementary materials.…”

Section: Methodsmentioning

confidence: 99%

“…KAFAK treatments are susceptible to peptidases in the blood and synovial fluid. To limit systemic exposure and premature degradation of KAFAK, our laboratory has designed poly N -isopropylacrylamide (pNIPAM) nanoparticle delivery systems to increase the peptide’s therapeutic lifetime (12–16). …”

Section: Introductionmentioning

confidence: 99%

“…In RAW 264.7 macrophages, an approximately 6-fold greater KAFAK release and improved anti-inflammatory response was seen with NGPEGSS compared to non-degradable NGPEGMBA counterparts (16). While Bartlett et al reported delivery of KAFAK to damaged cartilage in pH sensitive pNIPAm nanoparticles, the nanoparticles continuously degraded before reaching the target cell, thus limiting the therapeutic potential of the system (15).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Controlled release of anti-inflammatory peptides from reducible thermosensitive nanoparticles suppresses cartilage inflammation

Lin

Poh

Panitch

2016

Nanomedicine: Nanotechnology, Biology and Medicine

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Characterized by pain, cartilage degradation, and inflammation, osteoarthritis is often treated with anti-inflammatory therapies that provide short-term relief but can have adverse side effects; intra-articular drug delivery systems with controlled release of anti-inflammatory peptides using degradable poly(N-isopropylacrylamide) (pNIPAM) nanoparticles could prolong relief and minimize these side effects. Nanoparticles provide a biocompatible drug carrier that can protect encapsulated therapeutics from enzymatic degradation and increase payload delivery upon encountering a degradation stimulus. Here we demonstrate passive targeting of inflamed cartilage ex vivo by uptake of PEGylated pNIPAM nanoparticles with degradable disulfide crosslinks (abbreviated as NGPEGSS) into chondrocytes and subsequent intracellular release of an anti-inflammatory peptide KAFAKLAARLYRKALARQLGVAA (KAFAK). The KAFAK-loaded NGPEGSS treatment reduced ex vivo inflammation to a greater extent compared to its non-degradable counterparts. This study highlights a nanoparticle system that delivers therapeutics intracellularly with improved efficacy by triggered degradation and suppresses inflammation in multiple cell types within an inflamed joint.

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Bioresponsive Immunotherapeutic Materials

et al. 2023

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The human immune system is an interaction network of biological processes, and its dysfunction is closely associated with a wide array of diseases, such as cancer, infectious diseases, tissue damage, and autoimmune diseases. Manipulation of the immune response network in a desired and controlled fashion has been regarded as a promising strategy for maximizing immunotherapeutic efficacy and minimizing side effects. Integration of “smart” bioresponsive materials with immunoactive agents including small molecules, biomacromolecules, and cells can achieve on‐demand release of agents at targeted sites to reduce overdose‐related toxicity and alleviate off‐target effects. This review highlights the design principles of bioresponsive immunotherapeutic materials and discusses the critical roles of controlled release of immunoactive agents from bioresponsive materials in recruiting, housing, and manipulating immune cells for evoking desired immune responses. Challenges and future directions from the perspective of clinical translation are also discussed.

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Release of Anti-inflammatory Peptides from Thermosensitive Nanoparticles with Degradable Cross-Links Suppresses Pro-inflammatory Cytokine Production

Cited by 34 publications

References 43 publications

Prevention of Collagen-Induced Platelet Binding and Activation by Thermosensitive Nanoparticles

Prevention of Collagen-Induced Platelet Binding and Activation by Thermosensitive Nanoparticles

Controlled release of anti-inflammatory peptides from reducible thermosensitive nanoparticles suppresses cartilage inflammation

Bioresponsive Immunotherapeutic Materials

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