Conference Report: Second World Conference on Nanomedicine and Drug Delivery

The Second World Conference on Nanomedicine and Drug Delivery (WCN 2011) aimed to bring together researchers and developers from around the world working in prominent areas such as targeted delivery, diagnostics, regenerative medicine, cancer nanotechnology, plasmonic nanoparticles, biosensors, imaging techniques and biomedical applications. The conference featured more than 80 world-renowned speakers, who are among the top researchers and leaders in their fields. Its ultimate goal was to cultivate an open forum of ideas and collaborative efforts, alongside close cooperation and coordination with national and international colleagues. The conference was inaugurated by Yves Grohens (Director of Laboratoire d’Ingénierie des Matériaux de Bretagne [LIMATB] Lorient, France). In his inaugural talk, he discussed in brief the wide applications of nanomedicine. The development of a wide spectrum of nanoscale technologies is beginning to change the foundations of disease diagnosis, treatment and prevention. These technological innovations, referred to as nanomedicine, have the potential to turn molecular discoveries arising from genomics and proteomics into widespread benefit for patients. Nanomedicine is a large subject area and includes: nanoparticles that act as biological mimetics (e.g., functionalized carbon nanotubes [CNTs]); ‘nanomachines’ (e.g., those made from interchangeable DNA parts and DNA scaffolds such as octahedron and stick cube); nanofibers and polymeric nanoconstructs as biomaterials (e.g., molecular self-assembly and nanofibers of peptides and peptide-amphiphiles for tissue engineering, shape-memory polymers as molecular switches, nanoporous membranes); and nanoscale microfabrication-based devices (e.g., silicon microchips for drug release and micromachined hollow needles and 2D needle arrays from single-crystal silicon), sensors and laboratory diagnostics. Furthermore, there is a vast array of intriguing nanoscale particulate technologies capable of targeting different cells and extracellular elements in the body to deliver drugs, genetic materials and diagnostic agents specifically to these locations. Indeed, research into the rational delivery and targeting of pharmaceutical, therapeutic and diagnostic agents via intravenous and interstitial routes of administration with nanosized particles is at the forefront of projects in nanomedicine. The technical program included invited lectures as well as oral and poster presentations on the following topics:

• ▪ Synthesis and characterization of magnetic nanoparticles

• ▪ Targeted drug-delivery systems

• ▪ Diagnosis and treatment of cancer

• ▪ Photodynamic therapy

• ▪ Nano for tuberculosis

• ▪ Biosensors

• ▪ Tissue engineering

• ▪ Nanotoxicology

• ▪ Nanostructured materials

• ▪ Composites

Synthesis & characterization of nanoparticles

B Stephen Inbaraj (Fujen University, Taiwan) presented a paper on synthesis and characterization of magnetite nanoparticles modified with sodium and calcium salts of poly(γ-glutamic acid) (NaPGA and CaPGA), a nontoxic and hydrophilic biopolymer. The researcher demonstrated that the prepared magnetite nanoparticles are cytocompatible and possess antibacterial activity in vitro and thereby should be useful in in vivo studies for biomedical applications.

V Dive (Gif Sur Yvette, France) disclosed the toxicological aspect of multiwalled carbon nanotubes (MWCNTs). Using ¹⁴C radiolabeling of MWCNTs, he demonstrated that they can cross the lung barrier to reach lymph nodes and spleen in mice, with CNT biopersistence in organs 6 months after their injection. The ability of MWCNT to translocate from the lung to secondary organs may depend on their size, the protocol used to disperse MWCNT and the actual shape of the CNT (monodispersed or tangled) in lung tissue.

G Ferrini (Università Cattolica, Italy) delivered a lecture on optical and mechanical investigations of nanostructures for detection of biomolecules. He unveiled the possibility of studying biological samples without treatments using techniques such as optical detection based on evanescent wave spectroscopy; noncontact atomic force microscopy (NC-AFM); Femtosecond laser pulses used to excite thermal and mechanical transients in nanoengineered materials.

G Narasimha (Sri Venkateswara University, India), reported an eco-friendly route for the synthesis of sliver nanoparticles using Agaricus bisporus (white button mushroom) extract. These nanoparticles showed excellent antimicrobial activity against bacterial and fungal strains.

J Chamani (Islamic Azad University, Iran) investigated the interaction between human serum albumin (HSA) and ciprofloxacin in the presence of silver nanoparticles at physiological conditions (pH=7.4) using fluorescence spectroscopy and circular dichroism approaches. He stated that binding of ciprofloxacin to HSA could induce conformational changes in the macromolecule. With the help of a Stern–Volmer plot, he showed that the mechanism of fluorescence quenching of HSA with ciprofloxacin is static.

Nanodrug delivery

The research highlight of Ashok Patel (Unilever R&D, Netherlands) is on colloidal delivery systems for phytochemicals. In his presentation, an overview of the delivery challenges associated with representative phytochemicals was discussed and some of their current approaches based on the use of colloidal delivery systems for delivery of phytochemicals were illustrated with examples.

E Borowiak-Palen (West Pomeranian University of Technology, Poland) presented the study on synthesis and biocompatibility tests of silica nanospheres (SiO₂), mesoporues silica nanospheres (m-SiO₂), MWCNTs, functionalized MWCNTs and graphene.

M Edirisinghe (University College London, UK) described the recent methods developed for the preparation of drug carriers such as submicrometer-size porous particles, microbubbles and hollow capsules. He demonstrated the in situ incorporation of a range of active pharmaceutical ingredients such as estradiol, celecoxib and insulin in the products. He also conducted the diffusion studies to investigate the potential of the prepared structures as drug carriers.

R Pola (Institute of Macromolecular Chemistry, Czech Republic), designed a targeted drug-delivery system consisting of hydrophilic polymer-bearing drug and targeting protein, using click chemistry catalyzed by a ruthenium complex. The researcher has used coiled-coil peptides to attach the targeting protein to the polymer carrier without damaging the binding site of the protein. The recombinant protein was chosen as a targeting ligand against carbonic anhydrase IX, a receptor overexpressed by tumor cells of various human carcinomas. Doxorubicin (Dox) was bound to the polymer carrier via an enzymatically degradable amide bond. He said that the conjugate need to be tested for cytotoxicity and antitumor activity.

S Jain (National Institute of Pharmaceutical Education and Research, India) delivered a talk on nanocarriers, a powerful oral bioavailability enhancer tool for poorly absorbed or presystemically metabolized drugs. His research was mainly focused on tamoxifen (anticancer drug)-encapsulated PLGA nanoparticles, Dox (anticancer drug)-encapsulated PLGA nanoparticles, folic acid-coupled PEGylated PLGA nanocarriers for insulin, solid-lipid nanoparticles for oral delivery of amphotericin B and so on, which showed enhanced oral bioavailability, efficacy and reduced cytotoxicity.

L Jaeger (University of California, USA) delivered a lecture on self-assembling RNA particles as potential therapeutic delivery systems. He brought to light the importance of therapeutic RNA aptamers and siRNAs in the field of nanomedicine. His team has uncovered several RNA structural and assembly principles for RNA 3D structure prediction and rational design. He anticipates that his programmable RNA nanoparticles will be able to offer new approaches for the simultaneous delivery of multiple siRNAs and/or other functionalities for cellular therapeutics, in a similar fashion to strategies based on trimeric pRNA nanoparticles.

AR Thierry (SysDiag, France) designed lipid–DNA and plasmid–DNA complexes, lipoplex (Lx) for gene transfer and studied them comprehensibly to elucidate their formation and ultrastructure. The scholar checked the potential of this carrier to evaluate plasminogen activator inhibitor type I (PAI-1)-directed siRNA and to examine intracellular distribution of siRNA. Recently, the researcher’s team set up a unique formulation, Neutraplex (Nx), which allowed them to investigate the influence of the Lx surface charge in siRNA delivery without varying the lipid composition of the carrier.

M Pechar (Institute of Macromolecular Chemistry, Czech Republic) presented a paper on noncovalent attachment of recombinant proteins to polymer therapeutics. The principle of the method was based on the strong and noncovalent interaction between acetylcholine receptors and α-bungarotoxin (BTX). His team linked a peptide sequence, BTXbp to a reactive N-(2-hydroxypropyl) methacrylamide (HPMA)-based hydrophilic copolymer bearing antitumor drug, Dox. A fusion protein consisting of antiPSMA antibody scFv fragment and BTX (BTX-scFv) formed a noncovalent complex with the polymer–Dox–BTXbp conjugate. This system proved to be a universal tool for attachment of recombinant targeting proteins in a receptor-specific neoplastic treatment.

H Subban Ganapathy (Kumamoto University, Japan) has developed a novel biocompatible amphiphilic cyclodextrin, functionalized with fluorinated alkyl groups, which underwent self-assembly in aqueous solution to form spherical micelles. He demonstrated the use of these multifunctional cyclodextrin micelles for controlled delivery of Paclitaxel to cancer cells combined with efficient MRI contrast agents such as superparamagnetic iron oxide (SPIO) nanoparticles. In vitro cytotoxicity and MTT assay studies demonstrated the cytotoxic response of these multifunctional cyclodextrin micelles on A-549, human lung adenocarcinoma epithelial cell lines.

G Storm (Utrecht University, The Netherlands) investigated the use of RGD-peptide targeted PEG-coated nanoscale drug carriers for selective delivery of various drugs, including Dox, ZD6126 (a vascular disrupting agent) and siRNA. The in vivo studies demonstrated that RGD erythrocytes could delay tumor growth in a murine melanoma model, possibly through the induction of tumor infarctions.

S-H Chen (National Taipei University of Technology, Taiwan) presented a paper on applications of nanostructured materials and biomolecules for electrocatalysis and biosensors. He designed a biosensor by immobilizing glucose oxidase at gelatin-MWCNT-modified glassy carbon electrode through the well known glutaraldehyde chemistry and it demonstrated excellent sensitivity and stability. He discussed the preparation of silver nanoparticle-poly (3,4-ethylenedioxythiophene) (PEDOT) nanocomposite, a bimetallic hybrid film, PtAu and Au–Ag bimetallic nanoparticles, which showed good sensitivity and selectivity.

R Rajakumari (Mahatma Gandhi University, India) delivered a talk on the role of nanotechnology in dietary supplements. Her goal was to improve the functionality of vitamins and minerals while minimizing their concentration. She expects that nanoscale techniques will be most cost effective in the following areas of the food industry: development of new functional materials, food formulations, food processing at microscope and nanoscale levels, product development and storage.

L Bacakova (Institute of Physiology, Czech Republic) stated that nanodiamond (ND) is a promising material for regeneration and engineering of bone tissue modification of bone implants. The researcher discussed the methods for depositing nanocrystalline diamond (NCD) films on silicon substrates by a microwave plasma-enhanced chemical vapor deposition process and doped with boron in the gas phase. Boron doping was used to render the NCD films electrically conductive, which was expected to increase their attractiveness for cell colonization. In addition, she concluded that PLGA–ND scaffolds gave good support for the adhesion and growth of human bone-derived cells, and after some improvements, this material was promising for use in bone-tissue engineering.

F Fenili (Università degli Studi di Milano, Italy) reported novel examples of polyamidoamine (PAA) derivatives tailored for specific therapeutic applications in the field of nanomedicine and drug delivery. The expert’s research highlight was on 2-ethenyldithiopyridine-containing PAAs as intracytoplsmic vehicles of immunotoxines, PAA–cholesterol and PAA–β-cyclodextrin conjugate nanoparticles for the delivery of lipophilic drugs and paramagnetic PAAs for MRI applications.

I Banerjee (Birla Institute of Technology, India), presented a talk on synthesis of a magnetically active interpenetrating polymer network for biomedical applications. The interpenetrating polymer network was formed using hydrophobic polybutyl acrylate in the presence of iron oxide particles and hydrophilic poly-hydroxyethyl acrylate in the presence of benzoyl peroxide as initiator and ethylene glycol dimethacrylate as crosslinker. She was of the view that induced magnetic activity by iron oxide particles can be utilized in binding suitable enzymes, such as penicillin amidase from Escherichia coli, and targeted delivery.

P Millner (University of Leeds, UK) delivered a lecture on interfacing biomolecules with surfaces for nanomedicine; electrochemical immunosensors for diagnosis and targeted nanoparticles for intraoperative imaging. He succeeded in exploiting the properties of nanoparticles as vehicles for imaging colorectal cancers intraoperatively during laparoscopic procedures. He fabricated polymer- and silica-coated polymer nanoparticles in the size range of 25–1000 nm, with a wide range of pendant groups for biomolecule attachment. He expects that by the addition of an appropriate targeting antibody (e.g., anti-CEA) and fluorescent tag (organic fluors like Alexa and fluorescein, or inorganic Qdots) may yield a specific and bright optical imaging agent for colorectal cancers.

PM Dinh (University Paul Sabatier, France) conveyed about the chromophore effect in irradiated water clusters. In order to gain some insight on the microscopic mechanisms which take place in this chromophore effect, his research team studied a model system consisting of a Na atom (the chromophore) in contact with small water clusters (mimicking living tissues). The dynamical process investigated by his team was related to irradiation by an optical laser and the impact of this laser pulse, in terms of exciting energy and charge localization.

Nanostructured materials

T Simmet (University of Illinois, USA) revealed that nanosized carboxydextran-coated SPIO and ultrasmall SPIO (USPIO) were rapidly taken up by human macrophages in vitro by clathrin-mediated, scavenger receptor A-dependent endocytosis. According to him, USPIO induced more pronounced biochemical alterations and cytotoxicity, which could be antagonized by the JNK inhibitor V, when compared with SPIO. He proposed a therapeutic strategy to avoid SPIO-induced adverse effects.

W Fritzsche (Institute for Photonic Technology, Germany) delivered a talk on plasmonic nanoparticles for nanomedicine. He explained the principle of localized surface plasmon resonance, which can be used in sensors as well as manipulation at the nanoscale. He also added that light can induce a temperature increase up to a destruction of the particle, which can be utilized for the release of DNA or RNA even inside cells, or the selective destruction of cells or cell organelles upon specific binding, as demonstrated for metaphase chromosomes after in situ hybridization of labeled DNA probes.

B Pépin-Donat (Laboratoire d’Electronique Moléculaire Organique et Hybride, France) prepared composite polymer vesicles by two ways: by coating their membranes with two different pseudo-natural polyelectrolytes: chitosan (positively charged) and hyaluronan (negatively charged) and by encapsulating various responsive (thermo-mechanical) visco-elastic polymer systems based on poly-N-isopropylacrylamide (poly-NIPAM) in their internal medium. The researcher concluded his session by saying that all these composite polymer vesicles presented high potentiality as passive mechanical models of cells because of their improved structural and mechanical properties and as drug carriers because of their high stress resistance.

Nano for cancer

M Ahamed (King Saud University, Saudi Arabia) demonstrated that zinc oxide nanoparticles (ZnO NPs) and copper oxide nanoparticles (CuO NPs) induced DNA damage and apoptosis in A549 cells, which may be mediated through reactive oxygen species generation and oxidative stress. According to his results, the expression of Hsp70, the first-tier biomarker of cellular damage was induced by both nanoparticles. CuO NPs upregulated the cell-cycle checkpoint protein p53 and DNA damage biomarkers Rad51 and MSH2 expressions. ZnO NPs induced apoptosis via upregulation of p53 and bax proteins, inhibition of survivin and bcl-2 proteins and activation of caspase cascades.

M Novakova (Academy of Sciences of the Czech Republic, Czech Republic) synthesized and studied properties of novel biodegradable nanostructures prepared from graft copolymers assembled by the addition of metal ions. The graft copolymer consisted of backbone chelating polymeric chain poly(N-methyl methacryloylhydroxamic acid) with hydrophilic poly(ethylene oxide) grafts, which binds essential metal ions (Fe³⁺ or Cu²⁺). She stated that these synthesized polymeric structures have appropriate hydrodynamic diameter (60 nm) to exhibit enhanced permeation and retention effect and are designed to decompose (after fulfilling their task) into polymer chains with molecular weights under renal threshold so that they can be eliminated by kidneys.

R Boukherroub (Institut de Recherche Interdisciplinaire, France) focused on the preparation of hypericin-loaded lipid nanocapsules (size range of 25–100 nm) by a phase-inversion process, and their characterization in terms of size, charge and drug loading. He presented the results obtained on a systematic study undertaken to evaluate the influence of the lipid nanocapsules’ size and drug loading on the in vitro phototoxicity of the encapsulated hypericin, in comparison with free drug and, thereby, highlighted the importance of photodynamic therapy. V Bansal (RMIT University, Australia) discussed some of the multifunctional materials synthesized in their laboratory including metal alloy–metal oxide hybrid nanoparticles for antimicrobial applications, metal alloy-loaded fabrics for antimicrobial applications, metal and metal alloys for surface-enhanced Raman scattering, sensing of biological molecules, agnetite–silica hybrid structures for MRI of cancer tissues and multifunctional polymer nanocapsules for drug-delivery applications. Bansal also talked about current status quo of the field and the challenges ahead in the field to realize the full potential of nanomedicine.

Brain storming discussion

On the first day of the conference, there was a brain storming discussion led by A George, in which all of the national and international delegates participated. The topic of discourse was ‘India/EU/Rest of the World Joint Research Programme (Under FP7 Frame Work)’ and ‘DST India and Rest of the World Joint Collaboration’. Each of them gave a brief description of their ongoing projects and invited future collaborations. This discussion brought together all the research-related initiatives under a common roof playing a crucial role in reaching the goals of growth, competitiveness and establishment of a strong scientific foundation.

Concluding session

The concluding session was addressed by A George. Prizes were awarded for the best posters. Delegates expressed their gratitude that the second WCN 2011 had given them the opportunity to meet reputed scientists from many countries of the world to exchange methodologies and share research experiences on recent advancements in nanomedicine. The delegates also came forward to give their valuable feedback. Concerning the holding of a third conference on nanomedicine, all interventions were generally supportive for the need to hold such an event. However, several delegates requested that all the sessions be conducted in a single hall so that they can attend all the presentations. The Convener took note of these comments and announced that she would consider their suggestions in the next conference. All the distinguished guests thanked the organizers for their hospitality, grant cultural session and the wonderful boating trip through Vembanad Lake. The conference ended on a good note.