SELECTBIO

Nanomedicine 2014

In this work biocompatible and biodegradable NPs, with tunable hydrophobicity and biodegradation kinetics, were synthesized using novel Comb-Like Polymers (CLB). These NPs satisfy requirements for biological purpose for intravenous drug delivery in terms of size, between 20 and 300 nm, particle size distribution, biodegradability and biocompatibility. A number of obtained results for imaging (in vitro, ex vivo and in vivo), cell tracking (stem cells), cellular uptake studies, drug loading (antitumorals), toxicity studies, degradation and release studies are reported.

Biodegradable and Biocompatible Comb-Like Polymers for Biomedical Applications

The interaction of nanoparticles with body fluids may induce conformational changes in the proteins present in the medium. Such interactions could induce functional loss or important modifications in some proteins, and trigger cellular events induced by the NP-protein moiety. As metal oxide nanoparticles are widely used for various applications, the interaction of four different metal oxide nanoparticles (ZnO, TiO2, CeO2 and Al2O3) with three of the main protein fractions from human plasma (albumin, fibrinogen and globulins) was characterized by fluorescence and Fourier-transform infrared (FTIR) spectroscopy. The pattern of nanoparticle-protein interaction was shown to vary from a strong interaction with ZnO nanoparticles, which induced a decrease in the thermal stability of fibrinogen and albumin at a low temperature, and interferes with the clotting of fibrinogen, to a slight or null interaction with Al2O3 nanoparticles at physiological pH. The influence of pH was also characterized for albumin, with the interaction showing an important dependence on the surface charge of the nanoparticles. 
Metal oxide nanoparticles induced conformational changes in the secondary structure of albumin, principally the transformation of α-helices into β-sheet structures. This interaction, with the exception of Al2O3 nanoparticles at basic pH, could take place in domain II of the protein, formed mainly by hydrophobic and positive residues.

Conformational Changes Induced by  Nanomaterials: Functional Implications

The European Technology Platform on Nanomedicine (ETPN) is an initiative set-up in 2005 to define the strategic research priorities to be funded in the field, led by industry and officially recognized by the European Commission (EC) as part of the external advice and societal engagement needed to implement the coming Framework Program called Horizon 2020. The ETPN is addressing the application of nanotechnology to achieve breakthroughs in healthcare and conducted in the last year under the NANOMED2020 EU project several analyses, studies and interviews to map all actors in Nanomedicine in Europe and to define the needs for the successful translation of outstanding research into innovative products.&nbsp;

ETP Nanomedicine and NANOMED2020: Towards a New Nanomedicine Horizon

This lecture describes the application of green nanotechnology in cancer therapy. Phytochemicals from Tea, various fruits and herbs possess powerful antioxidants with redox potentials capable of reducing gold and other metal salts to their corresponding nano particles.  Our results have established that the phytochemicals serve dual roles of reduction and subsequent capping around nanoparticles to afford optimum in vivo stability as well as cancer cell receptor targeting properties.  The tremendous practicality of creating major oncological advances using green nanotechnological tools and also the power of this approach to connect traditional Herbal Medicine with Nanomedicine will be discussed.


Green Nanotechnology in Cancer Therapy

Solid drug nanoparticles (SDNs) have been produced commercially using technologies such as milling where large fragments of crystalised drug are ground into particles with diameters measurable in nanometers. This approach has been shown to overcome bioavailability issues for some poorly absorbed and insoluble drugs but does have some limitations because of incompatibility with drugs with certain physiochemical properties. Using a novel technology that produces SDNs through freeze drying or spray drying emulsions may be more broadly applicable across drugs. The application of this new approach to the formulation of poorly soluble antiretroviral drugs will be discussed, including benefits for oral bioavailability in pre-clinical species. The SDN formulations have shown the potential for reduced doses and benefits for paediatric administration formats for antiretroviral drugs. These formulations have undergone GMP manufacture and are in stability testing to support regulatory documentation for clinical evaluation in 2014.

Improved Oral Delivery of Antiretroviral Drugs Via A Novel Synthesis of Solid Drug Nanoparticle Formulations

Although the standard of care for lymphatic staging in breast cancer has been established for over two decades, the availability of the Sentinel Lymph Node Biopsy (SLNB) technique has been limited due to its reliance on radioisotopes.  Endomagnetics was founded to resolve availability through the application of magnetic nanoparticles and novel sensing technology.  SentiMag is an extremely sensitive hand-held magnetic susceptometer that can accurately detect minute concentrations of the nanoparticle tracer Sienna+, and the combined system has been approved for marketing in Europe since late 2011.  The system’s initial application was as an intra-operative medical device for sentinel node localisation in breast cancer, but it has shown promise in other indications such as melanoma, prostate and colorectal cancer.  By using magnetic nanoparticles, the technology overcomes the disadvantages of the current radioisotope-based technique – such as limited availability, poor workflow, short lifetime, and issues of specialist handling and exposure to radiation – to provide a lower cost, more patient-friendly alternative for clinicians. This could benefit as many as a quarter of a million more breast cancer patients in the West alone.  Dr Mayes will discuss Endomagnetics’ development of the system, the clinical performance of magnetic nanoparticles in lymphatic staging for breast cancer and the regulatory challenges leading to marketing authorisation.

Magnetic Nanoparticles in Surgical Oncology

Detection of disseminated tumor cells or tumor biomarkers in human fluids such as blood, urine, and saliva can provide an accessible tool for cancer detection and therapy monitoring. In particular, accurate quantitation of cancer cells in the bloodstream can help to determine prognosis and monitor the effectiveness of cancer therapy. However, the challenge of detecting circulating tumor cells (CTCs) is their rare occurrence, estimated as one to few CTCs among millions of leukocytes and billions of erythrocytes.
Here we address this challenging problem by developing nanoparticle probes with multiple functionalities. Integration of multiple components in a single nanostructure is a challenging task. Most of the existing approaches to synthesis of hybrid nanoparticles require cumbersome multi-step protocols and result in nanostructures with limited tunability of physical and optical properties. Here, we developed a new type of nanoparticles which consist of primary 6 nm iron oxide core-gold shell nanoparticles that form highly uniform spherical assemblies with sizes that can be varied from ca. 70 to 180 nm. The magneto-plasmonic nanoclusters exhibit strong red-NIR absorbance and superparamagnetic properties with a high magnetic moment in an external magnetic field. We conjugated the nanoclusters with monoclonal antibodies specific for tumor biomarkers of breast, colon and skin cancers and demonstrated molecular specific optical and photoacoustic (PA) imaging with high sensitivity. We carried out experiments in whole blood from a normal volunteer spiked with various amounts of cancer cells. It was shown that cell capture efficiency exhibits a linear behavior from 5 to 500 cells per 2.5 mL of the whole blood. Furthermore, we demonstrated that molecular targeted nanoclusters can be used for simultaneous magnetic capture and PA detection of cancer cells in whole blood with greater than 90% capturing efficiency with no laborious processing steps that are commonly used in other cancer cell capture and enumeration assays. The magneto-plasmonic nanoparticle platform is being tested in blood samples of cancer patients with metastatic disease with a very good capture efficiency as compared to FDA approved CellSearch system. Our immunotargeted nanoparticles can be easily adapted to a variety of biomarkers, targeting both surface receptor molecules and intracellular biomarkers of epithelialderived cancer cells. In this presentation we will explore the opportunities afforded by the hybrid magneto-plasmonic nanoparticles and PA imaging for the development of a low cost simple and nearly real-time assays for capture, separation and enumeration of rare cells.

Magneto-plasmonic Nanoparticle Platform for Capture, Separation and Enumeration of Rare Cells

This presentation will talk about context and challenges of therapeutic index in the pharmaceutical industry. The importance of therapeutic index improvement for Oncology and how nanoparticles can improve therapeutic index along with various case histories.

Nanomedicines to Improve the Therapeutic Index of Drugs in Modern Drug Design

Peptide nanofibres (PNFs) find many applications as biomaterials for tissue engineering and have also been studied for neuronal regeneration and brain delivery. Positively charged amphiphilic peptides able to self-assemble into PNFs have been engineered. These fiber-shaped nanoscale constructs can be exploited for the development of effective siRNA therapeutics. In this talk, we will illustrate recent experimental evidence on how peptide nanofibres (PNFs) can be designed as tools for siRNA-mediated gene silencing of specific and surgically-targeted brain foci. PNFs constitute promising nanoscale tools for intervention strategies in various neurological disorders.

Nanoparticle-mediated siRNA Gene Silencing against Brain Disorders

The formation of polymeric nanoparticles that are able to permeate gut monolayers, and deliver nanoparticles into the bloodstream, is a challenge to nanomedicine but allows the benefits of circulating nanoparticles without the need for injection. We have developed a new polymer architecture – termed hyperbranched polydendrons – that mimic dendrimers but provide considerable benefits at expected reduced costs.  Through combinations of branched vinyl polymerisation, linear-dendritic hybrid concepts and controlled polymerisation, complex polymer architectures that nanoprecipitate to form uniform nanoparticles have been generated. Encapsulation is possible and preliminary data has shown a lack of cytotoxicity with, but significant permeation through, gut epithelium monolayers. Our initial data and synthesis strategy is presented with options outlined for future development.  


Polydendrons: A New Nanoparticle Platform with Nanomedicine Opportunities

Porphyrins have played roles in the diagnosis and treatment of various diseases, in particular based on how these molecules interact with light. We will discuss some recent approaches to form novel nanostructured materials from porphyrins and related molecules. New self-assembled porphyrin nanomaterials have potentially enabling properties for disease diagnosis and therapy.


Self-assembled Porphyrin Nanomaterials for New Approaches to Medical Imaging and Therapy

The possibility of using genes as medicines to treat cancer is limited by the lack of efficacious delivery systems able to selectively deliver genes to tumours. We demonstrated that the intravenous administration of a tumour-targeted dendriplex led to tumour disappearance of 90% of the tested tumours over one month.

Tumour Regression After Intravenous Administration of Novel Tumour-targeted Nanomedicines

An overview of data describing translocation of nanomaterials following pulmonary, oral and intravenous, delivery and then relating this to local and distal effects (e.g. in the liver) including oxidative stress and inflammatory gene changes.  There is an urgent need for better in vitro alternatives for nanomaterial toxicity testing.  This study compares local and distal responses with in vitro responses to nanomaterials and identifies scenarios that work, that don’t work and makes suggested changes for the future.


Using In vitro and In vivo Models to Assess the Local and Systemic Responses to Nanomaterial Exposure

Why a dendritic approach to Nanomedicines?  Our main objective is to create dendrimers and dendronized hybrids at the nanoscale combining targeted detection properties by multi-modal medical imaging with therapeutic properties, supplying an image-guided therapy. The small size of the dendritic objects and the dendronized nanoparticles is mandatory as it allows envisaging a crossing of the capillary barrier, a urinary elimination and a favourable biodistribution: in vivo studies performed with dendritic 111In-radiopharmaceuticals on melanoma cancer and for the characterization of the sentinel lymph node, but also pre-clinical studies performed with dendronized iron oxides of various sizes and shapes will be discussed.

Biodegradable and Biocompatible Comb-Like Polymers for Biomedical Applications

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May 21, 2014

Nanomedicine 2014

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