Modular Peptide Amphiphile Micelles Improving an Antibody-Mediated Immune Response to Group A Streptococcus

Barrett, John C.; Ulery, Bret D.; Trent, Amanda; Liang, Simon; David, Natalie A.; Tirrell, Matthew

doi:10.1021/acsbiomaterials.6b00422

Cited by 37 publications

(51 citation statements)

References 39 publications

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“…However, given the ability to synthesize a broad range of sequence‐specific polypeptides and to append them to different molecules via post‐translation modifications, these examples represent only a small subset of all possible peptide‐based micelle structures. Peptide‐based micelles have been used for several immunomodulatory applications, including the delivery of i) PR8 virus antigen for mucosal immunity, ii) docetaxel and siRNA to knockdown an anti‐apoptotic gene for synergistic tumor therapy, iii) antigenic OVA, poly(I:C), and siRNA to knockdown STAT3 (an immunosuppressor), iv) influenza antigens and CpG ODNs to establish durable humoral immunity, v) Group A streptococcus B cell antigen (J8) to also induce humoral immunity, and vi) a photosensitizer and 1MT (an IDO inhibitor) to enable PDT for eradicating tumor lung metastases . Overall, peptide‐based micelles are a promising vehicle for delivering various immunomodulatory agents; however, a better understanding of their optimal size and loading parameters must be gained to fully benefit from their exquisite tunability.…”

Section: Nanoscale Materials For Immunotherapymentioning

confidence: 99%

Materials for Immunotherapy

et al. 2019

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Breakthroughs in materials engineering have accelerated the progress of immunotherapy in preclinical studies. The interplay of chemistry and materials has resulted in improved loading, targeting, and release of immunomodulatory agents. An overview of the materials that are used to enable or improve the success of immunotherapies in preclinical studies is presented, from immunosuppressive to proinflammatory strategies, with particular emphasis on technologies poised for clinical translation. The materials are organized based on their characteristic length scale, whereby the enabling feature of each technology is organized by the structure of that material. For example, the mechanisms by which i) nanoscale materials can improve targeting and infiltration of immunomodulatory payloads into tissues and cells, ii) microscale materials can facilitate cell‐mediated transport and serve as artificial antigen‐presenting cells, and iii) macroscale materials can form the basis of artificial microenvironments to promote cell infiltration and reprogramming are discussed. As a step toward establishing a set of design rules for future immunotherapies, materials that intrinsically activate or suppress the immune system are reviewed. Finally, a brief outlook on the trajectory of these systems and how they may be improved to address unsolved challenges in cancer, infectious diseases, and autoimmunity is presented.

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Section: Nanoscale Materials For Immunotherapymentioning

confidence: 99%

Materials for Immunotherapy

et al. 2019

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“…As nanoparticles have been shown to have promising self-adjuvanting properties (12,13), amphiphiles that self-assemble into them are often used in peptide vaccine delivery (14)(15)(16). For example, hydrophobic dendritic poly(tert-butyl acrylate) has previously been conjugated to a variety of peptide epitopes, including GAS-derived peptides, and the conjugates have been self-assembled to form particles (17).…”

Section: Introductionmentioning

confidence: 99%

Poly(amino acids) as a potent self-adjuvanting delivery system for peptide-based nanovaccines

et al. 2020

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To be optimally effective, peptide-based vaccines need to be administered with adjuvants. Many currently available adjuvants are toxic, not biodegradable; they invariably invoke adverse reactions, including allergic responses and excessive inflammation. A nontoxic, biodegradable, biocompatible, self-adjuvanting vaccine delivery system is urgently needed. Herein, we report a potent vaccine delivery system fulfilling the above requirements. A peptide antigen was coupled with poly-hydrophobic amino acid sequences serving as self-adjuvanting moieties using solid-phase synthesis, to produce fully defined single molecular entities. Under aqueous conditions, these molecules self-assembled into distinct nanoparticles and chain-like aggregates. Following subcutaneous immunization in mice, these particles successfully induced opsonic epitope-specific antibodies without the need of external adjuvant. Mice immunized with entities bearing 15 leucine residues were able to clear bacterial load from target organs without triggering the release of soluble inflammatory mediators. Thus, we have developed a well-defined and effective self-adjuvanting delivery system for peptide antigens.

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“…PAMs are also advantageous because they are biocompatible and have been shown to have a broad range of applications 32,33 . The water solubility of micelles offers an advantage over other nanoparticle-based systems such as certain polymeric nanoparticles that are not soluble in water and have to be suspended in solubilizers for injections 34 . Additionally, the ability to create PAMs that disassemble in response to a specific stimuli makes PAMs an attractive candidate for controlled intracellular drug delivery 35 .…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Monocyte-targeting Peptide Amphiphile Micelles for Imaging of Atherosclerosis

Poon

Sarkar

Chung

2017

JoVE

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Atherosclerosis is a major contributor to cardiovascular disease, the leading cause of death worldwide, which claims 17.3 million lives annually. Atherosclerosis is also the leading cause of sudden death and myocardial infarction, instigated by unstable plaques that rupture and occlude the blood vessel without warning. Current imaging modalities cannot differentiate between stable and unstable plaques that rupture. Peptide amphiphiles micelles (PAMs) can overcome this drawback as they can be modified with a variety of targeting moieties that bind specifically to diseased tissue. Monocytes have been shown to be early markers of atherosclerosis, while large accumulation of monocytes is associated with plaques prone to rupture. Hence, nanoparticles that can target monocytes can be used to discriminate different stages of atherosclerosis. To that end, here, we describe a protocol for the preparation of monocyte-targeting PAMs (monocyte chemoattractant protein-1 (MCP-1) PAMs). MCP-1 PAMs are self-assembled through synthesis under mild conditions to form nanoparticles of 15 nm in diameter with near neutral surface charge. In vitro, PAMs were found to be biocompatible and had a high binding affinity for monocytes. The methods described herein show promise for a wide range of applications in atherosclerosis as well as other inflammatory diseases.

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Modular Peptide Amphiphile Micelles Improving an Antibody-Mediated Immune Response to Group A Streptococcus

Cited by 37 publications

References 39 publications

Materials for Immunotherapy

Materials for Immunotherapy

Poly(amino acids) as a potent self-adjuvanting delivery system for peptide-based nanovaccines

Synthesis of Monocyte-targeting Peptide Amphiphile Micelles for Imaging of Atherosclerosis

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