Christina M. MacLaughlin

Phospholipid Membrane Encapsulation of Nanoparticles for Surface-Enhanced Raman Scattering

Lipid-encapsulated surface-enhanced Raman scattering (SERS) nanoparticles, with promising applications in biomedical diagnostics, were produced. Gold nanoparticles, 60 nm in diameter, were coated with a ternary mixture of DOPC, sphingomyelin, and cholesterol. The lipid layer is versatile for engineering the chemical and optical properties of the particles. The stability of the lipid-encapsulated particles is demonstrated over a period of weeks. The versatility of the layer is demonstrated by the incorporation of three different Raman-active species using three different strategies. The lipid layer was directly observed by TEM, and the SERS spectrum of the three dye species was confirmed by Raman spectroscopy. UV-vis absorption and dynamic light scattering provide additional evidence of lipid encapsulation. The encapsulation is achieved in aqueous solution, avoiding phase transfer and possible contamination from organic solvents. Furthermore, when fluorescent dye-labeled lipids were employed in the encapsulant, the fluorescence and SERS activity of the particles were controlled by the use of dissolved ions in the preparation solution.

Evaluation of SERS labeling of CD20 on CLL cells using optical microscopy and fluorescence flow cytometry.

UNLABELLED Immunophenotyping of lymphoproliferative disorders depends on the effective measurement of cell surface markers. The inherent light-scattering properties of plasmonic nanoparticles (NPs) combined with recent developments in NP design may confer significant advantages over traditional fluorescence probes. We report and evaluate the use of surface-enhanced Raman scattering (SERS) gold NPs (AuNPs) conjugated to therapeutic rituximab antibodies for selective targeting of CD20 molecules. SERS AuNPs were prepared by adsorbing a Raman-active dye onto the surface of 60 nm spherical AuNPs, coating the particles with 5 kDa polyethylene glycol, and conjugating rituximab to functional groups on polyethylene glycol. The effective targeting of CD20 on chronic lymphocytic leukemia cells by rituximab-conjugated SERS AuNPs was evaluated by dark-field imaging, Raman spectroscopy, and flow cytometry with both competitive binding and fluorescence detection procedures. Evidence of CD20 clustering within approximately 100 nm was observed. FROM THE CLINICAL EDITOR This study discusses the use of surface enhancement Raman scattering (SERS)-based plasmonic gold nanoparticles, which can be used for cell specific labeling. In this example rituximab, a commercially available CD20 humanized monoclonal antibody is used. Dark field imaging, Raman spectroscopy and flow cytometry was utilized to demonstrate the sensitive labeling capability of these gold nanoparticle based hybrid nanodevices.

Activatable fluorescence: From small molecule to nanoparticle.

Molecular imaging has emerged as an indispensable technology in the development and application of drug delivery systems. Targeted imaging agents report the presence of biomolecules, including therapeutic targets and disease biomarkers, while the biological behaviour of labelled delivery systems can be non-invasively assessed in real time. As an imaging modality, fluorescence offers additional signal specificity and dynamic information due to the inherent responsivity of fluorescence agents to interactions with other optical species and with their environment. Harnessing this responsivity is the basis of activatable fluorescence imaging, where interactions between an engineered fluorescence agent and its biological target induce a fluorogenic response. Small molecule activatable agents are frequently derivatives of common fluorophores designed to chemically react with their target. Macromolecular scale agents are useful for imaging proteins and nucleic acids, although their biological delivery can be difficult. Nanoscale activatable agents combine the responsivity of fluorophores with the unique optical and physical properties of nanomaterials. The molecular imaging application and overall complexity of biological target dictate the most advantageous fluorescence agent size scale and activation strategy.

Lipid-encapsulation of surface enhanced Raman scattering (SERS) nanoparticles and targeting to chronic lymphocytic leukemia (CLL) cells

60 nm diameter gold nanoparticles (AuNP) were coated with a ternary mixture of lipids and targeted to human lymphocytes. Previously, the versatility, stability and ease of application of the lipid coating was demonstrated by the incorporation of three classes of Raman-active species. In the present study, lipid encapsulated AuNPs were conjugated to two targeting species, namely whole antibodies and antibody fragments (Fab), by two methods. Furthermore, in vitro targeting of lipid-encapsulated Au nanoparticles to patient-derived chronic lymphocytic leukemia (CLL) cells was demonstrated by Raman spectroscopy, Raman mapping, and darkfield microscopy. These results further demonstrate the versatility of the lipid layer for imparting stability, SERS activity, and targeting capability, which make these particles promising candidates for biodiagnostics.

Porphysome nanoparticles for enhanced photothermal therapy in a patient-derived orthotopic pancreas xenograft cancer model: a pilot study

Abstract. Local disease control is a major challenge in pancreatic cancer treatment, because surgical resection of the primary tumor is only possible in a minority of patients and radiotherapy cannot be delivered in curative doses. Despite the promise of photothermal therapy (PTT) for focal ablation of pancreatic tumors, this approach remains underinvestigated. Using photothermal sensitizers in combination with laser light irradiation for PTT can result in more efficient conversion of light energy to heat and improved spatial confinement of thermal destruction to the tumor. Porphysomes are self-assembled nanoparticles composed mainly of pyropheophorbide-conjugated phospholipids, enabling the packing of ∼80,000 porphyrin photosensitizers per particle. The high-density porphyrin loading imparts enhanced photonic properties and enables high-payload tumor delivery. A patient-derived orthotopic pancreas xenograft model was used to evaluate the feasibility of porphysome-enhanced PTT for pancreatic cancer. Biodistribution and tumor accumulation were evaluated using fluorescence intensity measurements from homogenized tissues and imaging of excised organs. Tumor surface temperature was recorded using IR optical imaging during light irradiation to monitor treatment progress. Histological analyses were conducted to determine the extent of PTT thermal damage. These studies may provide insight into the influence of heat-sink effect on thermal therapy dosimetry for well-perfused pancreatic tumors.

Nanotexaphyrin: One-Pot Synthesis of a Manganese Texaphyrin-Phospholipid Nanoparticle for Magnetic Resonance Imaging

The discovery and synthesis of novel multifunctional organic building blocks for nanoparticles is challenging. Texaphyrin macrocycles are capable and multifunctional chelators. However, they remain elusive as building blocks for nanoparticles because of the difficulty associated with synthesis of texaphyrin constructs capable of self-assembly. A novel manganese (Mn)-texaphyrin-phospholipid building block is described, along with its one-pot synthesis and self-assembly into a Mn-nanotexaphyrin. This nanoparticle possesses strong resilience to manganese dissociation, structural stability, in vivo bio-safety, and structure-dependent T1 and T2 relaxivities. Magnetic resonance imaging (MRI) contrast enhanced visualization of lymphatic drainage is demonstrated with respect to proximal lymph nodes on the head and neck VX-2 tumors of a rabbit. Synthesis of 17 additional metallo-texaphyrin building blocks suggests that this novel one-pot synthetic procedure for nanotexaphyrins may lead to a wide range of applications in the field of nanomedicines.

Polymer-coated surface enhanced Raman scattering (SERS) gold nanoparticles for multiplexed labeling of chronic lymphocytic leukemia cells

The ease and flexibility of functionalization and inherent light scattering properties of plasmonic nanoparticles make them suitable contrast agents for measurement of cell surface markers. Immunophenotyping of lymphoproliferative disorders is traditionally undertaken using fluorescence detection methods which have a number of limitations. Herein, surface-enhanced Raman scattering (SERS) gold nanoparticles conjugated to monoclonal antibodies are used for the selective targeting of CD molecules on the surface of chronic lymphocytic leukemia (CLL) cells. Raman-active reporters were physisorbed on to the surface of 60 nm spherical Au nanoparticles, the particles were coated with 5kDa polyethylene glycol (PEG) including functionalities for conjugation to monoclonal IgG1 antibodies. A novel method for quantifying the number of antibodies bound to SERS probes on an individual basis as opposed to obtaining averages from solution was demonstrated using metal dots in transmission electron microscopy (TEM). The specificity of the interaction between SERS probes and surface CD molecules of CLL cells was assessed using Raman spectroscopy and dark field microscopy. An in-depth study of SERS probe targeting to B lymphocyte marker CD20 was undertaken, and proof-of-concept targeting using different SERS nanoparticle dyes specific for cell surface CD19, CD45 and CD5 demonstrated using SERS spectroscopy.

Photonic Nanoparticles for Cellular and Tissular Labeling

Nanotechnology has made significant contributions to biomedical sciences, and an important example is the pervasive use of colloidal nanoparticles, whose tunable optical properties and surface chemistries have contributed largely to their versatility. Prominent among these applications is their use as targeted optical probes in cellular and tissular investigations both in vivo and in vitro. This chapter focuses on metallic and semiconductor nanoparticles, summarizing their physical and optical properties, highlighting their advantage as fluorescence, colorimetric, Raman, and optoacoustic probes, and reviewing surface chemical modifications and particle targeting strategies. Current trends in research are illustrated through numerous examples from primary literature. The growing interest in pursuing medical applications has raised questions about their toxicity, biocompatibility, and long-term accumulation, and hence this chapter also examines current studies of cellular and animal toxicity and biodistribution of metallic and semiconductor nanoparticles. Growing trends and future perspectives in the field are highlighted.

Dual-Mode Dark Field and Surface-Enhanced Raman Scattering Liposomes for Lymphoma and Leukemia Cell Imaging

Multifunctional probes are needed to characterize individual cells simultaneously by different techniques to provide complementary information. A preparative method and an in vitro demonstration of function are presented for a dual-function dark field microscopy/surface-enhanced Raman scattering (SERS) liposome probe for cancer. Liposomes composed of zwitterionic lipids are valuable both to limit biofouling and to serve as a modular matrix to incorporate a variety of functional molecules and hence are used here as vehicles for SERS-active materials. Dark field microscopy and SERS represent new combined functionalities for targeted liposomal probes. Two methods of antibody conjugation to SERS liposomes are demonstrated: (i) direct conjugation to functional groups on the SERS liposome surface and (ii) postinsertion of lipid-functionalized antibody fragments (Fabs) into preformed SERS liposomes. In vitro experiments targeting both lymphoma cell line LY10 and primary human chronic lymphocytic leukemia (CLL) cells demonstrate the usefulness of these probes as optical contrast agents in both dark field and Raman microscopy.

Call for Papers for Zwitterionic Interfaces : Concepts and Emerging Applications

Applications W are planning to publish a collection of papers in autumn 2018 as a special issue in Langmuir, titled “Zwitterionic Interfaces: Concepts and Emerging Applications”. Langmuir authors have made important and timely contributions to this field, and we would like to highlight that through a special issue featuring impactful new articles. Generally, articles published in special issues of Langmuir are highly cited, and placing your work in a collection among experts in the field is excellent visibility for your article. Engineering materials with zwitterionic interfaces has emerged as a highly effective and increasingly adopted strategy, particularly in the production of environmentally benign and biocompatible materials with antifouling properties at the interface of biological environments. This approach is motivated by biology, in particular, by the presence of zwitterionic or alternating-charged groups on cell membranes and protein surfaces. We took inspiration for this issue, in part, from the third International Conference on Bioinspired and Zwitterionic Materials (ICBZM 2017) held in Tokyo, Japan, October 18− 20, 2017. This conference highlighted some of the most important advances in the field of zwitterionic materials and interfaces, from fundamental research to practical applications. These advances have significant implications in fields including biomaterials, biosensors, medical devices, tissue scaffolds, drug carriers, membranes, and marine coatings. As such, we want to bring this concept to Langmuir and to extend the invitation as an open call for papers. If you are interested in submitting a research article, please send an email stating your intent to special-issue@langmuir.acs. org. In response, you will receive a unique submission link with which to submit your manuscript. We request that you submit your manuscript by May 15, 2018 for it to be considered for inclusion in this issue. Once accepted, your article will be available online immediately. We are very excited about this issue and welcome the opportunity to work with previous Langmuir authors as well as newcomers to our journal. We hope that you will take part in this event and look forward to receiving your contribution. Shaoyi Jiang, Senior Editor University of Washington, Kazuhiko Ishihara, Guest Editor University of Tokyo, Yasuhiko Iwasaki, Guest Editor Kansai University, Julius Vancso, Guest Editor University of Twente Christina MacLaughlin, Development Editor ACS Publications ■ AUTHOR INFORMATION ORCID Julius Vancso: 0000-0003-4718-0507 Notes Views expressed in this editorial are those of the authors and not necessarily the views of the ACS.