The elimination or minimization of nonspecific biomolecule-material interactions is an integral part of refining the biological performance of existing and future biomaterials, as biofouling of surfaces can lead to compromised device performance, increased cost, and health concerns for the patient. In the emerging field of nanomedicine, for example, biointerfacial interactions play an important role in biodistribution, targeting and overall performance of nanomaterials. The long-term goals of this research are 1) to understand the fundamental biointerfacial phenomena surrounding interactions between engineered surfaces and biomolecules, with a specific emphasis on resistance of grafted polymers to nonspecific protein adsorption;and 2) to use this information to guide the design of novel antifouling peptide mimetic polymers for use in controlling biofouling of medical devices and nanoparticle therapeutics. To accomplish this, we will integrate experimental and theoretical approaches to study the antifouling properties of N-substituted glycine polymers (peptoids), and employ these peptoids as an integral component of a nanoparticle anticancer therapeutic. In the first and second aims, we will combine molecular theory with a versatile synthetic strategy and detailed experimental measurements of protein adsorption to develop novel antifouling peptoids. The focus will be on glycocalyx-mimetic peptoids (glycopeptoids), as well as N-methylglycine peptoid (sarcosine). The performance of these peptoids as surface-grafted polymers will be experimentally evaluated for resistance to nonspecific protein and cell fouling, and integration of these results with those obtained by molecular theory will allow us to understand the effects of chemical composition and chain architecture on fouling resistance.
In Aim 3, these peptoids will be grafted onto gold nanorods (AuNRs), modified with MUC1 antibody and investigated for anticancer efficacy in in-vitro and in-vivo model systems. An innovative aspect of this aim involves the use of theoretical predictions to guide the architectural and compositional design of peptoids to achieve bound surface densities and distributions that enhance the cellular uptake of anti-MUC1 modified AuNRs. In-vitro studies will probe glycopeptoid biocompatibility, cell-targeting efficiency, and photothermal cell ablation using the near-infrared plasmonic properties of the AuNRs. Finally, a xenograft tumor model will be used to demonstrate the efficacy of the anti-MUC1 modified AuNRs as a novel strategy for cancer therapy.
In this study we will combine theoretical and experimental approaches to study the antifouling properties of peptide mimetic polymers use this information to guide the design of polymer-modified anticancer therapeutics. The outcomes of this research will include enhanced understanding of protein-surface interactions and the development of novel strategies for cancer treatment.
|Gonzalez Solveyra, Estefania; Szleifer, Igal (2016) What is the role of curvature on the properties of nanomaterials for biomedical applications? Wiley Interdiscip Rev Nanomed Nanobiotechnol 8:334-54|
|Lau, King Hang Aaron; Sileika, Tadas S; Park, Sung Hyun et al. (2015) Molecular Design of Antifouling Polymer Brushes Using Sequence-Specific Peptoids. Adv Mater Interfaces 2:|
|Zelasko-Leon, Daria C; Fuentes, Christina M; Messersmith, Phillip B (2015) MUC1-Targeted Cancer Cell Photothermal Ablation Using Bioinspired Gold Nanorods. PLoS One 10:e0128756|
|Zhou, Jiajing; Wang, Peng; Wang, Chenxu et al. (2015) Versatile Core-Shell Nanoparticle@Metal-Organic Framework Nanohybrids: Exploiting Mussel-Inspired Polydopamine for Tailored Structural Integration. ACS Nano 9:6951-60|
|Ryu, Ji Young; Song, In Taek; Lau, K H Aaron et al. (2014) New antifouling platform characterized by single-molecule imaging. ACS Appl Mater Interfaces 6:3553-8|
|Kuang, Jinghao; Guo, Jason L; Messersmith, Phillip B (2014) High ionic strength formation of DOPA-melanin coating for loading and release of cationic antimicrobial compounds. Adv Mater Interfaces 1:|
|Black, Kvar C L; Sileika, Tadas S; Yi, Ji et al. (2014) Bacterial killing by light-triggered release of silver from biomimetic metal nanorods. Small 10:169-78|
|Black, Kvar C L; Yi, Ji; Rivera, JosÃ© G et al. (2013) Polydopamine-enabled surface functionalization of gold nanorods for cancer cell-targeted imaging and photothermal therapy. Nanomedicine (Lond) 8:17-28|
|Ham, Hyun Ok; Park, Sung Hyun; Kurutz, Josh W et al. (2013) Antifouling glycocalyx-mimetic peptoids. J Am Chem Soc 135:13015-22|
|Wei, Tao; Carignano, Marcelo A; Szleifer, Igal (2012) Molecular dynamics simulation of lysozyme adsorption/desorption on hydrophobic surfaces. J Phys Chem B 116:10189-94|
Showing the most recent 10 out of 28 publications