4:00pm - 4:30pmInvited
Leverage Physiology for Bioresponsive Medications
University of North Carolina at Chapel Hill, United States
Spurred by recent advances in materials chemistry, molecular pharmaceutics and nanobiotechnology, stimuli-responsive “smart” systems offer opportunities for precisely delivering drugs in dose-, spatial- and temporal-controlled manners. In this talk, I will discuss our ongoing efforts in using physiological signals, such as blood sugar level, enzyme activity and ATP gradient for on-demand drug delivery in a programmed manner. I will first present the glucose-responsive synthetic systems for biomimetic delivery of insulin for diabetes treatment. I will further discuss programmable delivery of anticancer therapeutics, the release of which can be activated in the tumor microenvironment or subcellular environment. Our latest studies on the local delivery of immune checkpoint inhibitors for enhanced cancer immunotherapy will be specifically introduced.
4:30pm - 5:00pmInvited
Molecular Imaging of Reactive Oxygen Species using Polymer Nanoparticles
Nanyang Technological University, Singapore
In vivo imaging of reactive oxygen and nitrogen species (RONS) is imperative to understand many pathological conditions, which however remains challenging due to the lack of reliable imaging probes. In this presentation, a unique approach to tackle this challenge using semiconducting polymer nanoparticles (SPNs) as the photonic imaging platform will be presented. The design and chemistry of SPN-based nanoprobes with different optical imaging modalities including fluorescence, chemiluminescence and photoacoustics will be discussed first. Then, applications of these nanoprobes in evaluation of drug-induced hepatotoxicity, imaging of neuroinflammation and monitoring of cancer therapeutic outcome will be detailed. At last, the potential of SPN in controlling the cellular machinery will be introduced.
5:00pm - 5:30pmInvited
Therapeutic Targeting of Pro-Inflammatory Macrophages
University of Illinois at Urbana-Champaign, United States
Inflammation is causally linked to numerous clinical pathologies, including cancer, heart disease, and type 2 diabetes. Pro-inflammatory macrophages have been widely implicated in the initiation and progression of these diseases and therefore are a key target for therapeutic intervention. We have recently developed a new macrophage targeting strategy for imaging agents and anti-inflammatory prodrugs that shows unusually high targeting efficiency to inflamed tissue in vivo. We observe more than 60% of an administered dose selectively distributes to inflamed adipose tissues of obese rodent models, and >90% of the targeted dose is associated with macrophages. Anti-inflammatory prodrugs delivered through this strategy demonstrate higher potency of inflammatory gene expression inhibition in adipose tissue compared with free drugs, and yield a trend toward systemic normalization 24 hours after a single dose. This strategy may be widely adopted for the detection and treatment of diseases associated with macrophage-mediated inflammation.
5:30pm - 5:45pmOral
A Dynamic Light Scattering Nanoplatform for High-Throughput Drug Screening Targeting p53 Pathway
Institute of Materials Research and Engineering, Agency for Science, Technology and Research (A*STAR), Singapore
The tumor suppressor p53 is a transcription factor regulating various critical cellular functions and is found to be inactivated by mutations in over 50% of all cancers. Thus, restoring p53 activity represents a very attractive way for cancer treatment. However, drug screening to identify a suitable lead compound has been proven to be very challenging. In this work, we report a label-free, ultrasensitive gold nanoparticle (AuNP)-based high-throughput drug screening platform targeting druggable p53 pathways. A dumbbell-shaped p53 specific DNA response element (RE) conjugated AuNPs was designed as unique sensing probe to measure the binding of drug activated p53 via dynamic light scattering (DLS) readout. A wildtype p53 protein binds specifically to the RE in a tetrameric form which will bridge the AuNP probes, resulting in a significant increase in the hydrodynamic size of the p53-RE-AuNPs. In contrast, mutant p53 proteins do not bind with RE sequence on the AuNPs, thus displaying negligible size change. Based on this sensing principle, this technology can be used to screen for the drugs that can activate/reactivate different p53-DNA binding in complex biological samples such as cell lysates directly without sacrificing its sensitivity and selectivity.This “mix-and-measure’ assay is operated in multi-well plates and allows rapid, sensitive, real-time and high-throughput measurements.
5:45pm - 6:00pmOral
Engineering Functional Neuronal Networks Using Nanowire Arrays
Australian National University, Australia
Introduction: Engineering neuronal circuits on artificial substrates provides insights into designing regenerative implants to interface with the nervous system. Advanced fabrication techniques in materials science are increasingly being used to create surface topographies (like grooves, pillars) for directing the growth of neuronal processes. Here, we grow neuronal cell cultures on vertically aligned semiconducting nanowires for guided neurite growth.
Methods: Vertically aligned nanowires on semiconductor wafers (Indium Phosphide and Silicon) were fabricated with top-down approach using electron beam lithography and reactive ion etching. The nanowires were in an isotropic arrangement with varying pitch of 1.5 μm – 5 μm and diameters ~ 100 nm - 800 nm. Primary cell cultures were obtained from hippocampal regions of the brain of Wistar rats aged 0-2 days. The cells were plated on the nanowire substrates, incubated at 37oC, 5% CO2 and grown for up to 21 days. Scanning electron microscopy (SEM) and immunocytochemistry were used for imaging the features of the cell/neurite growth on the nanowires, while a fluorogenic calcium indicator was used for imaging spontaneous activity of the cells.
Results: The SEM and immunocytochemistry images show that neuronal processes align along the nanowires. The dense interconnection between the cellular processes (axons and dendrites) and neuronal guidance occurs preferentially at the region of the nanowires.We also observed that the alignment of processes occurs at a nanowire pitch of < 2 μm and the growth is random above that pitch. We further show that cellular activity over a population of neurons growing on nanowires is highly synchronized compared to that on planar substrates.
Conclusion: Our results show that nanowires act as topographical cues for neuronal growth, resulting in the directional growth of the processes and highly interconnected neuronal network. We present a novel application of semiconducting nanowires for neural tissue engineering and regenerative medicine.
6:00pm - 6:15pmOral
The Influence of Variable of Polyethylene Oxide Content to Some Characteristics of PLA/CS Nanocomposite Films Loading Nifedipine
Institute for Tropical Technology, Vietnam Academy of Science and Technology, Vietnam
This paper presents effect of polyethylene oxide (PEO) content on some characteristics and properties of polylactic acid (PLA)/chitosan (CS) (80/20 wt/wt) nanocomposite films loading nifedipine (NIF). These nanocomposite films were prepared by solution method with various PEO content in the range of 0 to 10 wt.% in comparison with total weight of both PLA and CS. Infrared spectroscopy (IR), thermal gravimetric analysis (TGA), differential scanning calorimetry (DSC), field emission scanning electron microscopy (FESEM) and droplet size method were used to investigate the characteristics, properties, morphology, and hydrophilic/hydrophobic properties of the above composite films. In addition, the water absorption ability, efficiency of loading the drug, drug release and drug release kinetics, which are highlights of this paper, were also studied and discussed. The obtained results show that PEO plays an important role in improvement of interaction ability, dispersibility and compatibility between PLA, CS and NIF. At 6 wt.% of PEO, CS and NIF disperse in PLA matrix more regularly and smaller than at other PEO content. The glass temperature and relative crystal degree of the PLA/CS/NIF/PEO nanocomposite films are higher than those of the PLA/CS/NIF nanocomposite films without loading PEO. The hydrophobic property of the PLA/CS/NIF nanocomposite films is improved in the presence of PEO. The SEM images of the samples immersed in different pH solutions indicate that NIF had been released and made holes in chitosan phase. The NIF released from the PLA/CS/NIF nanocomposite films with and without PEO is complied with Zero order kinetic and mechanism of drug release is complex follows the Korsmeyer – Peppas model.
6:15pm - 6:30pmOral
Rapid Swelling and Highly Expandable Microneedles for In Situ Extraction of Skin Interstitial Fluid
1School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore; 2School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore; 3NTU-Northwestern Institute for Nanomedicine, Nanyang Technological University, Singapore
Skin interstitial fluid (ISF) is an emerging source used for monitoring of physiological systems and diagnosis of human diseases. Microneedles (MNs) show promises for extracting skin ISF, but there still remains issues, such as costly and complicated fabrication, risk of residue in skin and long-time administration on patient, which impede application of MNs. Here, we demonstrate a fast swelling and highly expandable MNs made of methacrylated hyaluronic acid (MeHA) for in situ extraction ISF. MeHA MNs can be simply fabricated and finally crosslinked under UV exposure. Due to the high water affinity of HA, the MNs can fast swell and expand to several times its initial volume with several minutes not only in PBS but also after insertion into agarose gel, without losing entire structure. Analytes, including RhoB, glucose and cholesterol, can be efficiently collected from MNs into microtubes for subsequent off-line analysis by simple centrifugation method. In vivo study demonstrate sufficient ISF (~2.3 ± 0.4 mg) of mice is extracted by each MN patch with retaining its structure in 10 min. Both glucose and cholesterol levels detected from MNs display similar trends as the levels detected by commercial glucose and cholesterol meters. This study strongly contributes to a minimally-invasive biomarkers detection, and opens up new avenues for application of polysaccharide hydrogel based on photo-crosslinking in design of MNs.