Biology subjects

Schulte, M. C.

Publications and source records attributed to Schulte, M. C..

3 recordsLinked to original sources

bioRxiv2024

Vasoactive Intestinal Peptide Amphiphile Micelle Material Properties Influence Their Cell Association and Internalization

Vasoactive intestinal peptide (VIP) is a promising anti-inflammatory peptide therapeutic that is known to induce biological effects by interacting with its cognate receptor (i.e., VPAC) on the surface of antigen presenting cells (APCs). For VIP-based drug delivery technologies like nano- and microparticles, little is known about the effect VPAC targeting has on APC behavior. This is further influenced by the fact that particulate material properties including chemistry, shape, and size are all known to influence APC behavior. In this study, peptide amphiphile micelles (PAMs) were employed as a modifiable platform to study the impact VPAC targeting and physical particle properties have on their association with macrophages. VIP amphiphile micelles (VIPAMs) and their scrambled peptide amphiphile micelle analogs (SVIPAMs) were fabricated from various chemistries yielding particle batches that were comprised of spheres (10 - 20 nm in diameter) and/or cylinders of varying lengths (i.e., 20 - 9000 nm). Micelle surface attachment to and internalization by macrophages were observed using confocal microscopy and their association was characterized by flow cytometry. The enclosed work provides strong evidence that macrophages rapidly bind VPAC specific micelles independent of physical properties though micelle shape and size as well as receptor-specificity all influence their long-term macrophage association. Specifically, a mixture of spherical and short cylindrical VIPAMs were able to achieve the greatest cell association which may correlate to their capacity to fully bind the VPAC receptors available on the surface of macrophages. These results provide the foundation of how nano- and microparticle physical properties and targeting capacity synergistically influence their capacity to associate with APCs.

bioengineering↗

bioRxiv2024

M2e-Derived Peptidyl and Peptide Amphiphile Micelles as Novel Influenza Vaccines

A significant problem with current influenza vaccines is their reliance on predictions of what will be the most prevalent strains for the upcoming season. Mismatches between predictions and reality in any given year can greatly reduce the overall efficacy of an immunization campaign. A universal influenza vaccine, which leverages epitopes conserved across many, if not all, strains of influenza, can reduce the need for such accurate forecasting. The ectodomain of the M2 ion channel protein is highly conserved and includes a B cell epitope in the M22-16 region, making it a potentially viable candidate as a universal influenza vaccine. Unfortunately, the use of free peptide antigens as vaccines comes with several disadvantages including poor stability and weak immunogenicity in vivo. However, integrating peptide antigens into nanoparticles can avoid some of those drawbacks. Previous studies have shown that micellar nanoparticles can be generated from peptides by conjugating them with a lipid or lipids. Specifically, hydrophobically-driven, self-assembled peptide amphiphile micelles comprised of Palm2K-peptide-(KE)4 have been found to be immunostimulatory. Unlike other peptides previously used for this purpose, the M22-16 peptide interestingly formed micelles without any peptidyl or lipid modifications. Because this unmodified peptide self-assembled on its own, it enabled the decoupling of the effect of micellization on immunogenicity from the incorporation of non-vaccine components such as the addition of a lipid moiety (Palm2K) and a zwitterion-like peptide block ((KE)4). The enclosed work shows that M22-16 peptidyl micelles had some characteristic differences in shape, critical micelle concentration, and secondary structure when compared to M22-16 peptide amphiphile micelles, which produced a few differences in murine antibody responses. These results suggest that peptide amphiphile micelles could be leveraged as a one-dose vaccine, while either micelle formulation induced strong immunological responses with a prime-booster immunization regimen.

bioengineering↗

bioRxiv2020

Lipidated poly(amino acid) nanostructures as versatile therapeutic delivery vehicles

Poly(amino acid)s are a diverse and capable class of polymers with significant potential for utilization in a wide variety of drug delivery applications. A sub-class of these biomaterials known as lipidated poly(amino acid)s (LPAAs) are amphiphiles composed of both hydrophobic and hydrophilic domains yielding interesting physical properties. In this article, we describe our efforts in developing a novel class of lysine and valine containing LPAAs synthesized via hexadecylamine initiated N-carboxyanhydride ring-opening polymerization (NCA-ROP). These highly hydrophobic LPAAs were found capable of undergoing hydrophobically-driven self-assembly into small nanostructures as well as being forced into larger nanostructures using a novel dump-and-stir nanoprecipitation process. This process yielded fine control over resulting nanoparticle size and cargo entrapment. Furthermore, cell-targeting DNA aptamer modification of doxorubicin-loaded LPAA nanoparticles induced significant death of co-incubated Non-Hodgkin Lymphoma cells providing exciting evidence of the therapeutic potential of this novel biomaterials-based delivery device.

bioengineering↗