SFNano welcomes excellent speakers from all over the world in 2017 in Bordeaux, France, extending the excellence of the presentations which were already observed in Paris in 2016.
Smart nanosystems making their way to the market for cancer treatment have been presented by Dr K. Kataoka and Pr P. Couvreur.
The enhanced permeability retention effect is still discussed as not all tumors accumulate nanoparticles. Dr K. Kataoka, from the Center of Nanomedicine in Japan, made a point on the accumulation of nanoparticles in vascularized and less vascularized tumors as a function of the nanoparticle size. He showed that nanoparticles below 30 nm could passively pass the tumoral endothelium, while bigger nanoparticles required tumor eruptions, bringing several nanoparticles at the same time as aggregates (Kataoka, Nature Nanotech 2016). He could therefore obtain in poorly vascularized pancreatic tumors a better efficacy with 30 nm polyions micells bearing Oxaliplatin. This technology using Calcium Phosphate in the core interacting with manganese revealed to be an excellent MRI contrast agent as the ration signal to noise was high due to the absence of background, a positive enhancement, and a pH-dependent release of Manganese which led to an increased signal in hypoxic region (Mi et al, Nature Nanotech 2016).
Pr Couvreur showed the benchtop to market success of livatagTM based on nanoparticles of polycyanoacrylate initially developed in his laboratory. He went through the limitations of nanoparticles as drug carriers explaining the low amount of NP on the market still (http://www.onxeo.com/). According to Pr Couvreur, burst release and poor drug loading are the main issues that the nanoparticles encountered. The ratio between drug and carrier should be higher, which is why he proposed carrier-drug-conjugates based on squalene amphiphiles. As an example squalene-gemcitabine conjugate was developed and his team showed that this conjugate actually benefits from LDL transport and interaction with their receptors to perform its effect on LDL-rich tumor cells. Adenosine squalene showed strong beneficial effects for brain ischemia (Nature Commun 2017).
Novel nanomedicine have been presented such as rational molecular design of peptidic nanostructures by C.Y. Lau, protein imprinted magnetic polymer by C. Boitard, synthesis of vinyl-ketene copolymers by J. Tran, self-assembled nanoparticles based on the Ouzo effect from F. Sciortino. Selenium presents antioxidant and anti-inflammatory activities. Se-NP have been proposed as anticancer agents. NANOCS Company prepared Se-NP with BSA and chitosan coating exhibiting 30 nm size. C. Bissardon proposed to study how Se-NP exert their anti-metastatic activity. E. Lepeltier proposed to use ferrocifen encapsulated into lipid nanocapsules with NFL peptide adsorbed at their surface. For glioblastoma treatment, Ferrocifens are produced by the company Feroscan and require encapsulation due to their low solubility.
Dr M. Grinstaff from Boston made an inspiring presentation on swelling nanoparticles which could gain 10 times its size according to the pH. The approach proposed was to inject them first to let them passively reach in the tumor and then the drug would be injected to accumulate in the swelled particles.
Win Hennink proposed Nanogels for intracellular delivery in dendritic cells.
Dextran nanogels were prepared by inverse mini emulsion polymerisation, dispersing in oil phase and polymerising under UV, then post loading antigen using small molecule with positively charged, loading antigen negatively charged. To avoid the release of the Ag, chemical immobilization of the protein with an additional linker made with thiol group
This formed positively charged nanogels better taken up by dendritic cells with Ovalbumine linked only released when using reductive agent. He obtained very impressive effect of Nanogels containing OVA+polyIC with reduced tumor growth B16 in vivo.
Nanohybrids made of lipid and polymer to deliver siRNA or mRNA were described by Jinjun Shi, from Harvard University (Theranostic 2017). He also shared with the audience the interest of melanin nanoparticles as antioxidant nanoparticles for brain ischemia. These nanoparticles behave as scavenging receptors for several radicals and act as dismutase (JACS 2017). Preliminary in vivo data are promising and require investigations on the mechanism of action.
Novel combined approaches using nanomedicine have been proposed such as photodynamic therapy with extravesicles containing THPC by M. Millard.
The advantage of magnetic nanoparticle is that magnetic hyperthermia is already in the clinic thanks to the company Magforce which provide a system to heat the particle. However, current particles do not heat enough but injection of large amount is not feasible due to the absence of degradation of the NP. NP which would degrade easily and heat more are required. T. Pellegrino and her team proposed iron oxide nanocubes. They improved the synthesis to be able to obtain various size of nanocubes ranging from 14 nm to 24 nm. Dr Pellegrino highlighted the importance of having stabilizing of each individual nanocube to avoid aggregation, but the necessity to induce aggregation to generate enough heat. Polymer temperature responsive are interesting polymers in this context to coat the nanocubes. Using hyperthermia with these coated cubes led to a great efficacy to avoid tumor growth. Biodegradation studies in collaboration with F. Gazeau revealed no MRI signal after 3 months.
Finally, Interest of nanoparticles for imaging and as sensors with various methodologies were presented.
Dr Y Cremillieux presented the interest of AGuIX® nanoparticles for MRI. Made of silanol groups, which bear 10 DOTA per particle of 3-5 nm, they are also of high interest for theranostic and entered clinical trial in patients with glioblastoma this year. MRI was performed post nebulization to observe the contrast agent in the lung at 50mM concentration in Gadolinium. Radiation was combined in lung cancer model 358-RVLuc and showed enhanced overall survival.
Surface-enhanced raman spectroscopy (SERS) get chemical information from raman and sensitivity from surface plasmons. These plasmons provide electromagnetic hot spots located in nanoscale junctions, acting as antenna transducing the raman signal nanoparticles can act as light amplifiers. Au and Ag NP are the mainly used NP for SERS however biomolecules do not bind to these NP. The idea proposed by A-I Henry from Northwestern University was to graft target at their surface to capture molecules such as glucose to obtain a sensor. As an example bis-boronic acid leads to 5 fold increase in glucose binding affinity compared to monoboric acid, and a 1-10 mM glucose sensing. Sensing hormones using FRET imaging has also been proposed by Chloe Grazon, to evaluate the loss of interaction between transcription factors and oligonucleotide due to hormones.
Gold nanoparticles in the form of ultrasmall nanoclusters were evaluated for NIRII imaging. NIRII corresponds to a window ranging between 850 and 1700 nm and may allow a deeper imaging at higher resolution. A particular attention was paid to control the hydrophobicity of these nanoclusters in order to modify their interaction of biological membranes. Effect on the association with radiotherapy of gold NP and Pt-NP were shown by R. Grall, CEA, Fontenay, to be dependent on the duration of the treatment
Dr L. Cognet presented Super-resolution imaging at video-rates on brain slices to investigate the movements of SWCNTs in the extracellular spaces (ECS). SWCNTs have the appropriated diameter, aspect ratio and rigidity in order to investigate the ECS as compared to small probes or polymers. Based on the known nanotube lengths, the diffusion of single SWCNTs, it is possible to better characterize the brain ECS in its nanoscale dimensions and to generate high-resolution spatial maps of its viscosity.
Biodegradability study of the inorganic nanoparticles proposed for imaging have been described by T. Lecuyer. Simulation of the passage of molecules through the membranes. It is an energy dependent process which takes milliseconds while endocytosis takes seconds. V. Baulin from Spain used a model to test if carbon nanotubes cross passively the membranes. The molecular simulation gives the energy cost required for the molecule to cross the membrane. The energy barrier was found at 150kT which is the energy required to break a covalent bond meaning that the particles should not cross the membrane. This value depends on the nature of the carbon nanotube +/- hydrophilic. The lower energy required was obtained for alternate layers of hydrophilic/hydrophobic nanotubes. Translocation is therefore possible, it is dependent on the nature of the particle. The nature also affects the formation of pores.