- Email: [email protected]
Local therapy for gastrointestinal cancer
Nanomedicine: Nanotechnology, Biology, and Medicine 12 (2016) 449 – 575 nanomedjournal.com
ChinaNanomedicine Abstracts
Polymeric nanomaterials for gene and vaccine delivery Chun Wang, Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, USA E-mail address: [email protected] Multifunctional polymers are arguably the most biomimetic platforms for engineering artificial gene carriers in gene therapy, because nucleic-acid-packaging agents found in nature, such as viral capsomeres and chromosomal histones, are all polymeric. Since last decade, much progress has been made toward designing cationic polymer gene carriers with high transfection efficiency and low cytotoxicity, and in elucidating the relationship between polymer structure and gene delivery performance. The first part of this presentation explores the role of cytotoxicity caused by cationic gene carriers. Polyplexes of polyethylenimine (PEI) and plasmid DNA induced apoptosis and autophagy in transfected cells. Manipulating such cellular responses through optimizing polyplex dosage or by adding small-molecule modulators could significantly enhance gene delivery efficiency. Furthermore, moderate level of polyplex-induced cytotoxicity could be beneficial in the context of DNA vaccine delivery, because it promoted acquisition and presentation of DNA-encoded antigen by dendritic cells (DCs), leading to antigen-specific activation of T cells. The second part of the presentation describes a chemically simple cationic polymer, poly(2-aminoethyl methacrylate) (PAEM), with surprisingly high efficiency in transfecting DCs that involved lipid rafts. Although polyplex transfection led to DC maturation and antigen-specific stimulation of T cells in vitro, it appeared that additional immunostimulatory adjuvants might be necessary for in vivo application, in which case, the timing of DC maturation and gene transfection would need to be carefully controlled. Finally, block copolymers of PAEM and PEG with well-defined chain-length were synthesized via controlled living polymerization to enable tuning the colloidal stability of polyplexes, tissue distribution, and transgene expression in vivo. (Funded by an NIH/NCI grant R01CA129189).
http://dx.doi.org/10.1016/j.nano.2015.12.002
Utilizing polydrug and polymeric drug concepts in development of nucleic acid delivery vectors David Oupicky, Center for Drug Delivery and Nanomedicine, University of NE Medical Center, USA, Department of Pharmaceutical Sciences, China Pharmaceutical University, Nanjing, China E-mail address: [email protected] (D. Oupicky) Polymer therapeutics is a class of delivery systems in which polymers either function as inert carriers for therapeutic agents (e.g., polymer–drug conjugates, polydrugs) or the polymers themselves fulfill the therapeutic function (i.e., polymeric drugs). We have recently applied the design concepts of polydrugs and polymeric drugs to the development of innovative polycations for delivery of therapeutic nucleic acids. Here, I will discuss recent advances in the development
of combination gene therapies based of self-immolative cationic polydrugs of an anticancer agent bisethylnorspermine that can simultaneously target dysregulated polyamine metabolism in cancer and deliver therapeutic genes. I will also discuss recently developed polymeric antagonists of the CXCR4 chemokine receptor that can function as dual-function polymeric drugs suitable for delivery of siRNA and microRNA and inhibition of cancer metastasis. http://dx.doi.org/10.1016/j.nano.2015.12.003
Local therapy for gastrointestinal cancer Don Haeng Lee, Department of Internal Medicine, Inha University School of Medicine, Incheon, South Korea, National Center of Efficacy Evaluation for the Development of Health Products Targeting Digestive Disorders, Incheon, South Korea, Utah-Inha DDS & Advanced Therapeutics Research Center, Incheon, South Korea Gastrointestinal malignancies include cancers of the esophagus, stomach, hepatobiliary system, pancreas, and small and large intestines. Prognosis and treatment are dependent on a variety of factors, including the type of GI cancer and stage at diagnosis. Treatment options include local and/or systemic therapies. Local therapy enables a therapeutic concentration of a drug to be administered to the desired target without exposing the entire body to a similar dose to decrease toxicity, increase efficacy and potentially modify biodistribution. It is with this in mind that several commercial products or clinical trials are followed in the local therapy for GI cancer such as transarterial chemoembolization (TACE), drug eluting stent (DES), photodynamic therapy (PDT), radiofrequency ablation (RFA), or endoscopic mucosal resection (EMR), endoscopic ultrasound guided (EUS)-guided injection (e.g., ethanol, gene, lipiodol), and endoscopic ultrasound guided (EUS)-guided fine needle injection (FNI). Among them, we carried out local therapy for GI cancer using DES and the purpose of our study was to evaluate the efficacy and safety of a developed drug eluting membrane containing Paclitaxel or Gemcitabine through in vitro and animal study. Drug eluting membrane was implanted in mice in which adenocarcinoma cell line was injected and grown in their back. The local therapy was found to have an anti-tumor effect on animal study. And also we did preliminary clinical trial of metallic stents covered with a paclitaxel-incorporated membrane (MSCPM) in the 21 patients with unresectable malignant biliary obstruction. Despite of limitation such as small number of patients and low rate of pathologic diagnosis, endoscopic insertion of MSCPM is technically feasible, safe, and effective in patients with malignant biliary obstruction. In addition, MSCPM may exert local anti-tumor activity because of the steady release of paclitaxel. We expect and hope DES will work effectively for tumor cells in diverse ways and, more importantly, will prolong stent patency and the patients' survival
1549-9634
Please cite this article as: ChinaNanomedicine Abstracts. Nanomedicine: NBM 2016;12:449-575, http://dx.doi.org/10.1016/j.nano.2016.02.001
450
ChinaNanomedicine Abstracts / Nanomedicine: Nanotechnology, Biology, and Medicine 12 (2016) 449–575
periods. But considerable investigation and a clinical study of DES will be required to achieve these goals. http://dx.doi.org/10.1016/j.nano.2015.12.004
Radio-nanomedicine: In vivo use of tracer radioisotope-labeled Dong Soo Lee, Nuclear Medicine, Seoul National University, Seoul, Korea E-mail address: [email protected] (D.S. Lee) Nanomedicine has recently been introduced for in vivo diagnosis and therapy as well as in vitro diagnosis. Classically, nuclear medicine had successfully used small molecules and bio-macromolecules. Nanomedicine claims that it can produce and control the use of nanomaterials whose sizes are several tens nanometers or around hundred nanometers in their diameters. In vivo nanomedicine tries to use inorganic substances as its material core such as silica particle, quantum dots, carbon tube/sheet, or Y-dopes Lu UCNP (upconversion nanoparticle; UCNP). These nanomaterials are composed of inorganic (hydrophobic) substances raise concerns regarding toxicity and biosafety. Hydrophilization and surface modification do not overcome all the concerns for in vivo use of nanomedicine. Nuclear medicine succeeded in using small molecules and bio-macromolecules in its long history and recently in applying radiolabeled peptides for diagnosis and therapy. Y-90 or Lu-177 labeled peptides were used for treating neuroendocrine tumors and Ga-68 was additionally used for diagnosing the metastatic sites as a prelude to the following Lu-177 PRRT and predicting the therapy response thereof. TRACE amount of small chemicals and macromolecules are used in nuclear medicine and tracing technology such as PET/ CT, SPECT/CT and PET/MRI are already available. Decreasing the amount of radiolabeled tracers enabled the administered materials easily compatible with the patients' body physiology and even evading the immune surveillance. This lesson can be taken advantage of to solve the problem of achieving vivo biosafety of nanomaterials. Nanomedicine will benefit from nuclear medicine in that they can reduce the amount of in vivo administered nano-core-materials to the least amount and finally use ‘trace’ amount. This will achieve much popular use of any nano (inorganic) core material for in vivo theranostic application while delivering the theranostic radionuclide on their surface. Nuclear medicine will benefit from nanomedicine in that nanomaterial will endow the vast surface of multiplex labeling of ligands, chelator, hydrophilizer and excretion-facilitators. Concomitant chelator on the surface will render the delivery of Lu-177 or other therapeutic compounds easier and ADME (absorption, distribution, metabolism and excretion) studies will enable the discovery of best choice of those nanomaterial-surface modifiers. Multiplexing will open the new possibility of better-individualized radionuclide treatment. For this purpose, multiplex simple and easy method of surface modification was warranted and Jeong's method of microencapsulation was one of the key solutions to this problem. Thus, if realized, the combination of nuclear medicine and nanomedicine shall yield unprecedented success of expanding the use of nanomaterials for use in clinical problem solving of in vivo theranostic. As an example, surface-modification using DOTA or NOTA upon the nanomaterials such as quantum dot, silica nanoparticle, UCNP, iron oxide enabled the concomitant labeling of Ga-68 and Lu-177 and simultaneous theragnosis was tried and recently reported in preclinical setting. This endeavor awaits prompt clinical application. http://dx.doi.org/10.1016/j.nano.2015.12.005
Nano-materials for LSPR and electrochemical biosensors Eiichi Tamiya, Department of Applied Physics, Osaka University, 2-1 Yamadaoka, Suita, Osaka, Japan E-mail address: [email protected] (E. Tamiya) We have studied successfully nano-structured biosensors based on the localized surface plasmon resonance (LSPR) and nanogold particles linked electrochemistry. Photonic plasmon spectra are caused by the refractive index variations that result from the binding of molecules to the metal nanostructures. There are optically
detectable parameters in biophotonics and biosensor devices. The bio-sensing of these nanostructures have been examined by label-free monitoring the biomolecular interactions in various flexible formats. Antibody–antigen and DNA hybridization reactions were performed to detect various biomarkers, with the detection limit of picogram levels. The multi-array format was constructed by a core–shell structured nanoparticle layer, which provided 300 spots on the sensing surface (Anal. Chem. 78, 6465, 2006). We demonstrated the capability of the array measurement using immunoglobulins, C-reactive protein, and fibrinogen. The detection limit of our label-free method was 100 pg/mL. A microfluidic biochip based on polydimethylsiloxane was used for real-time analysis and rapid detection. DNA and cellular signals from the target cells can be monitored by our system. DNA amplification process (PCR) and monoclonal antibody production from hybridoma cell library can be monitored (Anal. Chim. Acta, 66,111, 2010). Electrochemistry measurements connecting to LSPR chips were successfully exploited in a simultaneous detectable scheme. The binding of melittin to lipid membrane was measured using localized surface plasmon resonance, and the permeability of the lipid membrane was then assessed electrochemically as a function of melittin with the purpose of seeking a novel, sensitive detection system for peptide toxins (Anal. Chem. 80,1859, 2008). These nanoporous structures were transferred to the cyclo-olefin polymer film surface from the porous mold by a thermal nanoimprinting process. A plasmonic substrate was fabricated by sputtering a thin layer of gold onto this nanopillar polymer structure and the refractive index response in a variety of media was evaluated. Finally, the biosensing capacity of this novel plasmonic substrate was verified by analysis of human immunoglobulin and achieved a minimum detection limit of 1.0 ng/mL. With the advantages of mass production with consistent reproducibility stemming from the nanoimprint fabrication process, our gold-capped polymeric pillars are ready for the transition from academic interest into commercialization systems for practical use in diagnostic applications (Anal. Chem. 84, 5494, 2012). Surface Enhanced Raman Scattering (SERS) was also discussed with gold and silver nanoparticles interacting with bio-molecules. Gold nanoparticles were successfully delivered into single cells. Spatiotemporal measurements of SERS fingerprints suggested the dynamic molecular interactions and transformations taking place at different locations with time in cardiomyocytes (PLoS One, 6(8), e22801, 2011). Gold nanoparticleantibody can be linked with new electrochemical immunoassay as GLEIA (gold linked electrochemical immunoassay). High sensitive detection of human chorionic gonadotropin (0.36 pg/mL) and insulin (0.1 ng/mL) was reported (Electroanalysis, 20, 14, 2008). http://dx.doi.org/10.1016/j.nano.2015.12.006
Nanomedicine: Need for a new (nano)pharmacology and (nano)toxicology Harald F. Krug, International Research Cooperation Manager, Empa—Swiss Federal Laboratories for Materials, Science and Technology, Lerchenfeldstr. 5, St. Gallen, Switzerland E-mail address: [email protected] (H.F. Krug)
The implementation of nanotechnological approaches in medicine started several decades ago, but the hype on new techniques and sophisticated products is much younger (see figure). The specialty of certain nanoobjects to have very new properties with regard to their chemical, physical but also biological behavior opens a wide range of different applications, but leads also to some concern about their possible side effects within living organisms and the environment. Is the pharmacokinetics different compared to conventional drugs? Are they interacting with the immune system? Do they move everywhere within the body or can they be targeted or controlled? Do they possibly transport other critical substances to places that those never would have reached without their nano-vehicles? These and more critical questions came up during the past years and should be taken carefully into consideration when thinking about new developments in the field of nanomedicine. The last 5-6 years have witnessed an exponential increase in the numbers of publications on “Nanotoxicology” too. More and more it becomes apparent that many of these publications contain shortcomings in characterization of the tested material, experimental design and the conclusions drawn. Obviously, these limitations offer difficulties in issuing clear statements on “Safety Aspects of Nanomaterials”. What is missing is the reliability on the data presented in the studies, as many published data are inconsistent with each other. Not only we could
ChinaNanomedicine Abstracts
Polymeric nanomaterials for gene and vaccine delivery Chun Wang, Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, USA E-mail address: [email protected] Multifunctional polymers are arguably the most biomimetic platforms for engineering artificial gene carriers in gene therapy, because nucleic-acid-packaging agents found in nature, such as viral capsomeres and chromosomal histones, are all polymeric. Since last decade, much progress has been made toward designing cationic polymer gene carriers with high transfection efficiency and low cytotoxicity, and in elucidating the relationship between polymer structure and gene delivery performance. The first part of this presentation explores the role of cytotoxicity caused by cationic gene carriers. Polyplexes of polyethylenimine (PEI) and plasmid DNA induced apoptosis and autophagy in transfected cells. Manipulating such cellular responses through optimizing polyplex dosage or by adding small-molecule modulators could significantly enhance gene delivery efficiency. Furthermore, moderate level of polyplex-induced cytotoxicity could be beneficial in the context of DNA vaccine delivery, because it promoted acquisition and presentation of DNA-encoded antigen by dendritic cells (DCs), leading to antigen-specific activation of T cells. The second part of the presentation describes a chemically simple cationic polymer, poly(2-aminoethyl methacrylate) (PAEM), with surprisingly high efficiency in transfecting DCs that involved lipid rafts. Although polyplex transfection led to DC maturation and antigen-specific stimulation of T cells in vitro, it appeared that additional immunostimulatory adjuvants might be necessary for in vivo application, in which case, the timing of DC maturation and gene transfection would need to be carefully controlled. Finally, block copolymers of PAEM and PEG with well-defined chain-length were synthesized via controlled living polymerization to enable tuning the colloidal stability of polyplexes, tissue distribution, and transgene expression in vivo. (Funded by an NIH/NCI grant R01CA129189).
http://dx.doi.org/10.1016/j.nano.2015.12.002
Utilizing polydrug and polymeric drug concepts in development of nucleic acid delivery vectors David Oupicky, Center for Drug Delivery and Nanomedicine, University of NE Medical Center, USA, Department of Pharmaceutical Sciences, China Pharmaceutical University, Nanjing, China E-mail address: [email protected] (D. Oupicky) Polymer therapeutics is a class of delivery systems in which polymers either function as inert carriers for therapeutic agents (e.g., polymer–drug conjugates, polydrugs) or the polymers themselves fulfill the therapeutic function (i.e., polymeric drugs). We have recently applied the design concepts of polydrugs and polymeric drugs to the development of innovative polycations for delivery of therapeutic nucleic acids. Here, I will discuss recent advances in the development
of combination gene therapies based of self-immolative cationic polydrugs of an anticancer agent bisethylnorspermine that can simultaneously target dysregulated polyamine metabolism in cancer and deliver therapeutic genes. I will also discuss recently developed polymeric antagonists of the CXCR4 chemokine receptor that can function as dual-function polymeric drugs suitable for delivery of siRNA and microRNA and inhibition of cancer metastasis. http://dx.doi.org/10.1016/j.nano.2015.12.003
Local therapy for gastrointestinal cancer Don Haeng Lee, Department of Internal Medicine, Inha University School of Medicine, Incheon, South Korea, National Center of Efficacy Evaluation for the Development of Health Products Targeting Digestive Disorders, Incheon, South Korea, Utah-Inha DDS & Advanced Therapeutics Research Center, Incheon, South Korea Gastrointestinal malignancies include cancers of the esophagus, stomach, hepatobiliary system, pancreas, and small and large intestines. Prognosis and treatment are dependent on a variety of factors, including the type of GI cancer and stage at diagnosis. Treatment options include local and/or systemic therapies. Local therapy enables a therapeutic concentration of a drug to be administered to the desired target without exposing the entire body to a similar dose to decrease toxicity, increase efficacy and potentially modify biodistribution. It is with this in mind that several commercial products or clinical trials are followed in the local therapy for GI cancer such as transarterial chemoembolization (TACE), drug eluting stent (DES), photodynamic therapy (PDT), radiofrequency ablation (RFA), or endoscopic mucosal resection (EMR), endoscopic ultrasound guided (EUS)-guided injection (e.g., ethanol, gene, lipiodol), and endoscopic ultrasound guided (EUS)-guided fine needle injection (FNI). Among them, we carried out local therapy for GI cancer using DES and the purpose of our study was to evaluate the efficacy and safety of a developed drug eluting membrane containing Paclitaxel or Gemcitabine through in vitro and animal study. Drug eluting membrane was implanted in mice in which adenocarcinoma cell line was injected and grown in their back. The local therapy was found to have an anti-tumor effect on animal study. And also we did preliminary clinical trial of metallic stents covered with a paclitaxel-incorporated membrane (MSCPM) in the 21 patients with unresectable malignant biliary obstruction. Despite of limitation such as small number of patients and low rate of pathologic diagnosis, endoscopic insertion of MSCPM is technically feasible, safe, and effective in patients with malignant biliary obstruction. In addition, MSCPM may exert local anti-tumor activity because of the steady release of paclitaxel. We expect and hope DES will work effectively for tumor cells in diverse ways and, more importantly, will prolong stent patency and the patients' survival
1549-9634
Please cite this article as: ChinaNanomedicine Abstracts. Nanomedicine: NBM 2016;12:449-575, http://dx.doi.org/10.1016/j.nano.2016.02.001
450
ChinaNanomedicine Abstracts / Nanomedicine: Nanotechnology, Biology, and Medicine 12 (2016) 449–575
periods. But considerable investigation and a clinical study of DES will be required to achieve these goals. http://dx.doi.org/10.1016/j.nano.2015.12.004
Radio-nanomedicine: In vivo use of tracer radioisotope-labeled Dong Soo Lee, Nuclear Medicine, Seoul National University, Seoul, Korea E-mail address: [email protected] (D.S. Lee) Nanomedicine has recently been introduced for in vivo diagnosis and therapy as well as in vitro diagnosis. Classically, nuclear medicine had successfully used small molecules and bio-macromolecules. Nanomedicine claims that it can produce and control the use of nanomaterials whose sizes are several tens nanometers or around hundred nanometers in their diameters. In vivo nanomedicine tries to use inorganic substances as its material core such as silica particle, quantum dots, carbon tube/sheet, or Y-dopes Lu UCNP (upconversion nanoparticle; UCNP). These nanomaterials are composed of inorganic (hydrophobic) substances raise concerns regarding toxicity and biosafety. Hydrophilization and surface modification do not overcome all the concerns for in vivo use of nanomedicine. Nuclear medicine succeeded in using small molecules and bio-macromolecules in its long history and recently in applying radiolabeled peptides for diagnosis and therapy. Y-90 or Lu-177 labeled peptides were used for treating neuroendocrine tumors and Ga-68 was additionally used for diagnosing the metastatic sites as a prelude to the following Lu-177 PRRT and predicting the therapy response thereof. TRACE amount of small chemicals and macromolecules are used in nuclear medicine and tracing technology such as PET/ CT, SPECT/CT and PET/MRI are already available. Decreasing the amount of radiolabeled tracers enabled the administered materials easily compatible with the patients' body physiology and even evading the immune surveillance. This lesson can be taken advantage of to solve the problem of achieving vivo biosafety of nanomaterials. Nanomedicine will benefit from nuclear medicine in that they can reduce the amount of in vivo administered nano-core-materials to the least amount and finally use ‘trace’ amount. This will achieve much popular use of any nano (inorganic) core material for in vivo theranostic application while delivering the theranostic radionuclide on their surface. Nuclear medicine will benefit from nanomedicine in that nanomaterial will endow the vast surface of multiplex labeling of ligands, chelator, hydrophilizer and excretion-facilitators. Concomitant chelator on the surface will render the delivery of Lu-177 or other therapeutic compounds easier and ADME (absorption, distribution, metabolism and excretion) studies will enable the discovery of best choice of those nanomaterial-surface modifiers. Multiplexing will open the new possibility of better-individualized radionuclide treatment. For this purpose, multiplex simple and easy method of surface modification was warranted and Jeong's method of microencapsulation was one of the key solutions to this problem. Thus, if realized, the combination of nuclear medicine and nanomedicine shall yield unprecedented success of expanding the use of nanomaterials for use in clinical problem solving of in vivo theranostic. As an example, surface-modification using DOTA or NOTA upon the nanomaterials such as quantum dot, silica nanoparticle, UCNP, iron oxide enabled the concomitant labeling of Ga-68 and Lu-177 and simultaneous theragnosis was tried and recently reported in preclinical setting. This endeavor awaits prompt clinical application. http://dx.doi.org/10.1016/j.nano.2015.12.005
Nano-materials for LSPR and electrochemical biosensors Eiichi Tamiya, Department of Applied Physics, Osaka University, 2-1 Yamadaoka, Suita, Osaka, Japan E-mail address: [email protected] (E. Tamiya) We have studied successfully nano-structured biosensors based on the localized surface plasmon resonance (LSPR) and nanogold particles linked electrochemistry. Photonic plasmon spectra are caused by the refractive index variations that result from the binding of molecules to the metal nanostructures. There are optically
detectable parameters in biophotonics and biosensor devices. The bio-sensing of these nanostructures have been examined by label-free monitoring the biomolecular interactions in various flexible formats. Antibody–antigen and DNA hybridization reactions were performed to detect various biomarkers, with the detection limit of picogram levels. The multi-array format was constructed by a core–shell structured nanoparticle layer, which provided 300 spots on the sensing surface (Anal. Chem. 78, 6465, 2006). We demonstrated the capability of the array measurement using immunoglobulins, C-reactive protein, and fibrinogen. The detection limit of our label-free method was 100 pg/mL. A microfluidic biochip based on polydimethylsiloxane was used for real-time analysis and rapid detection. DNA and cellular signals from the target cells can be monitored by our system. DNA amplification process (PCR) and monoclonal antibody production from hybridoma cell library can be monitored (Anal. Chim. Acta, 66,111, 2010). Electrochemistry measurements connecting to LSPR chips were successfully exploited in a simultaneous detectable scheme. The binding of melittin to lipid membrane was measured using localized surface plasmon resonance, and the permeability of the lipid membrane was then assessed electrochemically as a function of melittin with the purpose of seeking a novel, sensitive detection system for peptide toxins (Anal. Chem. 80,1859, 2008). These nanoporous structures were transferred to the cyclo-olefin polymer film surface from the porous mold by a thermal nanoimprinting process. A plasmonic substrate was fabricated by sputtering a thin layer of gold onto this nanopillar polymer structure and the refractive index response in a variety of media was evaluated. Finally, the biosensing capacity of this novel plasmonic substrate was verified by analysis of human immunoglobulin and achieved a minimum detection limit of 1.0 ng/mL. With the advantages of mass production with consistent reproducibility stemming from the nanoimprint fabrication process, our gold-capped polymeric pillars are ready for the transition from academic interest into commercialization systems for practical use in diagnostic applications (Anal. Chem. 84, 5494, 2012). Surface Enhanced Raman Scattering (SERS) was also discussed with gold and silver nanoparticles interacting with bio-molecules. Gold nanoparticles were successfully delivered into single cells. Spatiotemporal measurements of SERS fingerprints suggested the dynamic molecular interactions and transformations taking place at different locations with time in cardiomyocytes (PLoS One, 6(8), e22801, 2011). Gold nanoparticleantibody can be linked with new electrochemical immunoassay as GLEIA (gold linked electrochemical immunoassay). High sensitive detection of human chorionic gonadotropin (0.36 pg/mL) and insulin (0.1 ng/mL) was reported (Electroanalysis, 20, 14, 2008). http://dx.doi.org/10.1016/j.nano.2015.12.006
Nanomedicine: Need for a new (nano)pharmacology and (nano)toxicology Harald F. Krug, International Research Cooperation Manager, Empa—Swiss Federal Laboratories for Materials, Science and Technology, Lerchenfeldstr. 5, St. Gallen, Switzerland E-mail address: [email protected] (H.F. Krug)
The implementation of nanotechnological approaches in medicine started several decades ago, but the hype on new techniques and sophisticated products is much younger (see figure). The specialty of certain nanoobjects to have very new properties with regard to their chemical, physical but also biological behavior opens a wide range of different applications, but leads also to some concern about their possible side effects within living organisms and the environment. Is the pharmacokinetics different compared to conventional drugs? Are they interacting with the immune system? Do they move everywhere within the body or can they be targeted or controlled? Do they possibly transport other critical substances to places that those never would have reached without their nano-vehicles? These and more critical questions came up during the past years and should be taken carefully into consideration when thinking about new developments in the field of nanomedicine. The last 5-6 years have witnessed an exponential increase in the numbers of publications on “Nanotoxicology” too. More and more it becomes apparent that many of these publications contain shortcomings in characterization of the tested material, experimental design and the conclusions drawn. Obviously, these limitations offer difficulties in issuing clear statements on “Safety Aspects of Nanomaterials”. What is missing is the reliability on the data presented in the studies, as many published data are inconsistent with each other. Not only we could