Daishun Ling

The surface science of nanocrystals

All nanomaterials share a common feature of large surface-to-volume ratio, making their surfaces the dominant player in many physical and chemical processes. Surface ligands - molecules that bind to the surface - are an essential component of nanomaterial synthesis, processing and application. Understanding the structure and properties of nanoscale interfaces requires an intricate mix of concepts and techniques borrowed from surface science and coordination chemistry. Our Review elaborates these connections and discusses the bonding, electronic structure and chemical transformations at nanomaterial surfaces. We specifically focus on the role of surface ligands in tuning and rationally designing properties of functional nanomaterials. Given their importance for biomedical (imaging, diagnostics and therapeutics) and optoelectronic (light-emitting devices, transistors, solar cells) applications, we end with an assessment of application-targeted surface engineering.

Iron Oxide Based Nanoparticles for Multimodal Imaging and Magnetoresponsive Therapy

Magnetoresponsive Therapy Nohyun Lee, Dongwon Yoo, Daishun Ling,†,‡,⊥ Mi Hyeon Cho, Taeghwan Hyeon,*,†,‡ and Jinwoo Cheon* †Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 151-742, Korea ‡School of Chemical and Biological Engineering, Seoul National University, Seoul 151-742, Korea Department of Chemistry, Yonsei University, Seoul 120-749, Korea School of Advanced Materials Engineering, Kookmin University, Seoul 136-702, Korea Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China

Theranostic Probe Based on Lanthanide-Doped Nanoparticles for Simultaneous In Vivo Dual-Modal Imaging and Photodynamic Therapy

Dual-modal in vivo tumor imaging and photodynamic therapy using hexagonal NaYF(4):Yb,Er/NaGdF(4) core-shell upconverting nanoparticles combined with a photosensitizer, chlorin e6, is reported. Tumors can be clearly observed not only in the upconversion luminescence image but also in the magnetic resonance image. In vivo photodynamic therapy by systemic administration is demonstrated under 980 nm irradiation.

Chemical Design of Biocompatible Iron Oxide Nanoparticles for Medical Applications

Iron oxide nanoparticles are one of the most versatile and safe nanomaterials used in medicine. Recent progress in nanochemistry enables fine control of the size, crystallinity, uniformity, and surface properties of iron oxide nanoparticles. In this review, the synthesis of chemically designed biocompatible iron oxide nanoparticles with improved quality and reduced toxicity is discussed for use in diverse biomedical applications.

Multiple‐Interaction Ligands Inspired by Mussel Adhesive Protein: Synthesis of Highly Stable and Biocompatible Nanoparticles

Theprerequisiteforthesuccessfulbiomedicaluseofnanoparticles is their colloidal stability in harsh biologicalenvironments. One main approach to render nanoparticleswater-dispersible is replacing the hydrophobic cappingligands with hydrophilic ones that harbor anchoring groupssuch as carboxylic acids, thiols, phosphines, and amines;

Hyaluronic acid-conjugated graphene oxide/photosensitizer nanohybrids for cancer targeted photodynamic therapy

Hyaluronic acid (HA)-graphene oxide (GO) conjugates, with a high loading of photosensitizers (PS; Ce6), were developed as a cancer cell targeted and photoactivity switchable nanoplatform for photodynamic therapy (PDT). HA-GO conjugates with size below 100 nm were first prepared by the chemical conjugation between ADH-modified HA and fractionated GO sheets with size relevant for drug delivery. Before evaluating the drug delivery efficacies, their chemical structure, morphology, and biocompatibility were characterized by 1H NMR, UV, TGA, AFM, DLS and MTT assays. The physical adsorption of Ce6 onto HA-GO nanocarriers was mainly due to the π-π stacking as well as hydrophobic interactions. It was demonstrated by CLSM and FACS that the cellular internalization of the HA-GO/Ce6 nanohybrids was much more effective when compared with free Ce6, which was also found to be significantly influenced by the co-treatment with an excess amount of HA polymers, illustrating their active targeting to HA receptors overexpressed on cancer cells. The photoactivity of Ce6 adsorbed on HA-GO nanocarriers was mostly quenched in aqueous solution to ensure biocompatibility, but was quickly recovered after the release of Ce6 from HA-GO nanocarriers upon cellular uptake. As a result, the PDT efficiency of the HA-GO/Ce6 nanohybrids was remarkably improved ∼10 times more than that of free Ce6, as well demonstrated in both MTT and LIVE/DEAD assays.

Bioresorbable Electronic Stent Integrated with Therapeutic Nanoparticles for Endovascular Diseases

Implantable endovascular devices such as bare metal, drug eluting, and bioresorbable stents have transformed interventional care by providing continuous structural and mechanical support to many peripheral, neural, and coronary arteries affected by blockage. Although effective in achieving immediate restoration of blood flow, the long-term re-endothelialization and inflammation induced by mechanical stents are difficult to diagnose or treat. Here we present nanomaterial designs and integration strategies for the bioresorbable electronic stent with drug-infused functionalized nanoparticles to enable flow sensing, temperature monitoring, data storage, wireless power/data transmission, inflammation suppression, localized drug delivery, and hyperthermia therapy. In vivo and ex vivo animal experiments as well as in vitro cell studies demonstrate the previously unrecognized potential for bioresorbable electronic implants coupled with bioinert therapeutic nanoparticles in the endovascular system.

An endoscope with integrated transparent bioelectronics and theranostic nanoparticles for colon cancer treatment

The gastrointestinal tract is a challenging anatomical target for diagnostic and therapeutic procedures for bleeding, polyps and cancerous growths. Advanced endoscopes that combine imaging and therapies within the gastrointestinal tract provide an advantage over stand-alone diagnostic or therapeutic devices. However, current multimodal endoscopes lack the spatial resolution necessary to detect and treat small cancers and other abnormalities. Here we present a multifunctional endoscope-based interventional system that integrates transparent bioelectronics with theranostic nanoparticles, which are photoactivated within highly localized space near tumours or benign growths. These advanced electronics and nanoparticles collectively enable optical fluorescence-based mapping, electrical impedance and pH sensing, contact/temperature monitoring, radio frequency ablation and localized photo/chemotherapy, as the basis of a closed-loop solution for colon cancer treatment. In vitro, ex vivo and in vivo experiments highlight the utility of this technology for accurate detection, delineation and rapid targeted therapy of colon cancer or precancerous lesions.

Parallel Comparative Studies on Mouse Toxicity of Oxide Nanoparticle- and Gadolinium-Based T1 MRI Contrast Agents

Magnetic resonance imaging (MRI) contrast agents with high relaxivity are highly desirable because they can significantly increase the accuracy of diagnosis. However, they can be potentially toxic to the patients. In this study, using a mouse model, we investigate the toxic effects and subsequent tissue damage induced by three T1 MRI contrast agents: gadopentetate dimeglumine injection (GDI), a clinically used gadolinium (Gd)-based contrast agent (GBCAs), and oxide nanoparticle (NP)-based contrast agents, extremely small-sized iron oxide NPs (ESIONs) and manganese oxide (MnO) NPs. Biodistribution, hematological and histopathological changes, inflammation, and the endoplasmic reticulum (ER) stress responses are evaluated for 24 h after intravenous injection. These thorough assessments of the toxic and stress responses of these agents provide a panoramic description of safety concerns and underlying mechanisms of the toxicity of contrast agents in the body. We demonstrate that ESIONs exhibit fewer adverse effects than the MnO NPs and the clinically used GDI GBCAs, providing useful information on future applications of ESIONs as potentially safe MRI contrast agents.

Surface design of magnetic nanoparticles for stimuli-responsive cancer imaging and therapy

Magnetic nanoparticles (MNPs) have been extensively studied for their potential applications to cancer diagnosis and treatment. However, various obstacles limit the use of nanoparticles for delivery in the tumor microenvironment. As a viable solution to such obstacles, advances in nanoparticle surface engineering augmented by a profound understanding of cancer physiology present new opportunities for MNP-based imaging and therapeutic agents. Stimuli-responsive ligands, rationally designed to interact with various physicochemical aspects, can improve the performance of MNPs in cancer-targeted imaging and therapy. In this review, we highlight recent progress in the design of MNP-based stimuli-responsive nanomaterials and their applications to cancer diagnosis and treatment.