10:30am - 11:00amInvited
Near Infrared Cancer Photoimmunotherapy Can Enhance Nano-Drug Delivery
National Cancer Institute, United States
Near infrared photoimmunotherapy (NIR-PIT) is a newly developed, molecularly-targeted cancer photo-theranostic technology based on conjugating a near infrared silica-phthalocyanine dye, IRdye700DX (IR700) to a monoclonal antibody thereby targeting specific cell-surface molecules. A first-in-human Phase 1 clinical trial of NIR-PIT with the cetuximab-IR700 (RM1929) targeting EGFR in patients with inoperable head and neck cancer was approved by the US FDA in April 2015, and is now in transition to a Phase 2 trial (https://clinicaltrials.gov/ct2/show/NCT02422979). When exposed to NIR light, the conjugate rapidly induces a highly-selective, necrotic/immunogenic cell death (ICD) only in antigen-positive MAb-IR700-bound cancer cells. ICD occurs as early as 1 minute after exposure to NIR light and results in irreversible morphologic changes on target-expressing cells including cellular swelling, bleb formation, and rupture of vesicles due to membrane damage. Meanwhile, immediately adjacent receptor-negative cells are totally unharmed. Dynamic 3D observation of tumor cells undergoing NIR-PIT along with novel live cell microscopies showed rapidly swelling in treated cells immediately after light exposure suggesting rapid water influx into cells. Cell biological analysis showed that ICD induced by NIR-PIT rapidly maturate immature dendritic cells adjacent to dying cancer cells initiating a host anti-cancer immune response. Additionally, NIR-PIT can enhance nano-drug delivery into the treated tumor bed up to 24-fold compared with untreated tumors, a phenomenon that we have termed the “super-enhanced permeability and retention” (SUPR) effect. Furthermore, NIT-PIT targeting immuno-suppressor cells, such as Treg, in a local tumor, can enhance tumor cell-selective systemic host-immunity leading to significant responses in distant metastatic tumors. In conclusion, due to it highly targeted cancer cell-selective cytotoxicity, NIR-PIT carries few side effects and healing is rapid. NIR-PIT induces ICD on cancer cells that initiates host immunity. Moreover, NIR-PIT can locally deplete immune suppressor cells infiltrating in tumor beds, thus, activating systemic anti-cancer cellular immunity without potential autoimmune adverse effects.
11:00am - 11:30amInvited
Synthesis of Functional Noble Metal Nanomaterials for Bioanalytical Applications
Korea University, South Korea
Noble metal nanomaterials exhibit a variety of unique chemical and physical properties, such as intense optical properties in UV-vis spectroscopy or surface-enhanced Raman scattering (SERS), and easy fabrication of the surface nature using functional ligands. Conventionally, these noble metal nanomaterials, when conjugated with DNA, can be programmed to assemble reversibly, which allows one to build up a number of versatile assay schemes for the detection of various disease markers. Importantly, the interparticle interactions of those DNA-conjugates are fundamentally based on (1) the chemical recognition properties of DNA, and (2) the size or shape of the noble metal nanomaterials. These interesting properties have led to a number of fundamental developments for the assembly formation of the nanoparticles and their diagnostic applications.
To address these issues, the development of chemical library-based approaches for the synthesis of noble metal nanomaterials with controlled in-plate and on-plate structures is demonstrated first in this presentation. Furthermore, the fundamental and general non-Watson–Crick base-pairing interactions of divalent metal ions (M2+s) with the DNA-conjugates are explored to investigate the coordinative nature of M2+ and single-stranded DNA as an effective driving force to synthesize monodisperse assembly structures of DNA-conjugates. Bioanalytical applications of these controlled structures for detecting diseases markers are qualitatively and quantitatively investigated in detail in model systems.
11:30am - 11:45amOral
Heavy at the Nano-scale: Effect of Nanoparticle Density on Endothelial Barrier Function
1School of Materials Science and Engineering, Nanyang Technological University, Singapore; 2School of Biological Sciences, Nanyang Technological University, Singapore; 3Deparment of Chemical and Biomolecular Engineering, National University of Singapore, Singapore
The endothelial cell junctions plays an important role in the regulation of vascular permeability and integrity. Recently, we have shown that inorganic nanoparticles (NPs) such as TiO2, SiO2 and hydroxyapatite NPs, within 30 minutes of treatment time, are able to disrupt VE-cadherin interaction between adjoining endothelial cells to induce endothelial leakiness (nanoparticle induced endothelial leakiness, NanoEL). Herein, we demonstrate that particle density, an often over-looked physical determinant in nano-bio interaction, is a critical modulator of NanoEL. Using a panel of consistently sized silica nanoparticles (SiNPs) with different effective densities (ρE), it was found that the threshold ρE to trigger NanoEL is between 1.57 g/cm3 to 1.72 g/ cm3. It was also found that a cumulative gravitational-mediated force of approximately 1.8 nN/ µm along the boundaries of VE-cadherin junctions appeared to be a critical inception force to disrupt endothelial cell-cell adhesion. This resulted in the “snapping” of the mechanically pre-tensed VE-cadherin (Nanosnap) to form micron-sized gaps that would dramatically increase endothelial leakiness. Our findings not only provided critical insights into the key determinants of NPs in the regulation of endothelial barrier function but also unveiled an exploitable strategy for nanomedicine.
11:45am - 12:00pmOral
Highly-Biocompatible and Multifunctionalizable Systems based on Nanocrystalline Apatites for Advanced Biomedical Applications
1CIRIMAT, UMR CNRS/INPT/UPS 5085, Université de Toulouse, France; 2IUCT Oncopole - Institut Claudius Régaud, France
The use of calcium phosphate-based bioceramics in medicine has long attracted interest, especially for bone repair, due to similarities with bone mineral. During the last years, biomimetic nanocrystalline apatites have in particular been a focus for several biomedical studies (e.g. [1-5]) due to an exceptional surface reactivity allowing ion exchange and molecular adsorptions.
In this contribution, several medical strategies will be presented to illustrate the potential of such systems, whether as scaffolds for activated bone regeneration with drug release capabilities or as colloidal individualized nanoparticles (with sizes down to 30 nm and possibly made luminescent) for other domains of applications such as cellular diagnosis and/or intracellular drug delivery (e.g. for oncology).
 Nanomedicine: Interaction of biomimetic apatite colloidal nanoparticles with human blood components
M. Choimet, K. Hyoung-Mi, J-M. Oh, A. Tourrette, C. Drouet,
Coll. Surf. B: Biointerfaces, 145 (2016) 87-94, doi:10.1016/j.colsurfb.2016.04.038
 Adsorption of tranexamic acid on hydroxyapatite: Toward the development of biomaterials with local hemostatic activity
S. Sarda, F. Errassifi, O. Marsan, A. Geffre, C. Trumel, C. Drouet,
Mater. Sci. Eng. C, 66 (2016) 1-7, doi:10.1016/j.msec.2016.04.032
 Superparamagnetic iron-doped nanocrystalline apatite as a delivery system for doxorubicin
M. Iafisco, C. Drouet, A. Adamiano, P. Pascaud, M. Montesi, S. Panseri, S. Sarda, A. Tampieri
J. Mater. Chem. B 4 (2016) 57, doi:10.1039/c5tb01524c
 Biomimetic Apatite-Based Functional Nanoparticles as Promising Newcomers in Nanomedicine: Overview of 10 Years of Initiatory Research
C. Drouet, A. Al-Kattan, M. Choimet, A. Tourrette, V. Santran, J. Dexpert-Ghys, B. Pipy, F. Brouillet, M. Tourbin
Journal of General Practice and Medical Diagnosis (J Gen Pract Med Diagn) 1 (2015) 1-9
 Progress on the preparation of nanocrystalline apatites and surface characterization: Overview of fundamental and applied aspects
J. GOMEZ-MORALES, M. IAFISCO, J.M. DELGADO-LOPEZ, S. SARDA, C. DROUET
Progr. Cryst. Growth Charact. Mater. 59 (2013) 1-46, doi: 10.1016/j.pcrysgrow.2012.11.001
12:00pm - 12:15pmOral
Peptide Delivery with Poly(ethylene glycol) Diacrylate Microneedles through Swelling Effect
Nanyang Technological University, Singapore
(Polyethylene glycol) diacrylate (PEGDA) based microneedles, with good biocompatibility, are easily fabricated through photo-polymerization with a precisely controlled structure. It has successfully been used for the transdermal delivery of small molecular drugs such as 5-fluorouracil. However, the delivery of peptide based therapeutics using this platform is rarely seen. This is because of the potential damage to the peptide during the photo-polymerization process of PEGDA. Herein, we introduce a method for loading PEGDA microneedles with peptides without the concern of the disruption. Taking gap junction inhibitor (Gap 26) as an example, the peptide is loaded into PEGDA microneedles through the swelling effect of PEGDA in the aqueous solution. The final device is tested in a keloid scar model for the potential therapeutic effects.